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OBJECTIVE@#To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes.@*METHODS@#The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C. C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase a (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters.@*RESULTS@#PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P<0.05). Compared with the H/R group, up-regulated expression of AMPKα, GLUT4, PFK2, FAT/CD36 and ACC2 were observed, and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group (P<0.05). These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group (P<0.05).@*CONCLUSION@#PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders, by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.
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Objective:To observe the effects of Shenma Yizhi prescription(SMYZ)on learning and memory, inflammatory factors and oxidative stress related indexes of rats with chronic cerebral ischemia inducing vascular dementia caused by bilateral common carotid artery ligation. Method:The chronic cerebral ischemia model of SPF grade SD rats was prepared by bilateral common carotid artery ligation. After successful surgery, the rats with cognitive impairment were randomly divided into 5 groups,model, donepezil(0.45 mg·kg-1), SMYZ-low, medium and high dose(2.97,5.94,11.88 g·kg-1), with 10 rats in each group, and 10 rats in sham operation group were established. Intragastric administration were given for 8 weeks respectively then followed Morris water maze test. The pathomorphological changes of hippocampus CA1 were observed. The serum levels of acetylcholine(Ach)and acetylcholinesterase (AChE)were detected, and the levels of inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum of rats were detected. The contents of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase reductase (GSH-Px) were observed. Result:Compared with sham operation group, the escape latency increased significantly in the model group, and the frequency of platform search, the frequency of crossing the original platform and the percentage of swimming time in the original platform quadrant decreased significantly (P<0.05,P<0.01). The contents of Ach and the contents of GSH and GSH-Px were significantly decreased (P<0.05,P<0.01). The contents of AChE, IL-1β and TNF-α and the contents of MDA were significantly increased (P<0.05,P<0.01). Compared with model group, the escape latency of rats in the in the low, medium and high dose groups of SMYZ prescription was significantly reduced (P<0.05,P<0.01).The frequency of looking for a platform, the frequency of crossing the original platform and the percentage of swimming time in the original platform quadrant of the rats in the low, medium and high dose groups of SMYZ prescription increased significantly (P<0.05,P<0.01). The content of AChE in high dose group were significantly reduced(P<0.01), and the content of Ach in high dose group were significantly increased(P<0.05), the rat serum IL-1β, TNF-α levels and MDA content were significantly reduced(P<0.05,P<0.01). The GSH, SOD and GSH-Px levels were significantly increased (P<0.05,P<0.01). Conclusion:SMYZ can improve the learning and memory ability of rats with vascular cognitive disorder caused by chronic cerebral ischemia caused by ligation of bilateral common carotid artery, bilateral common carotid artery ligation, improve the pathological morphology of hippocampal tissue, inhibit inflammatory response, improve cholinergic level and oxidative stress state.
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OBJECTIVE@#To assess the effect and safety of Huannao Yicong Formula (, HYF) in the treatment of patients with mild-to-moderate Alzheimer's disease (AD).@*METHODS@#Sixty patients with mild-tomoderate AD were evenly randomized into HYF group and donepezil group with the random number method. Patients in the HYF group took 5 g of HYF granules twice daily and 5 mg placebo of donepezil once daily. Patients in the donepezil group took 5 mg donepezil once daily and 5 g placebo of HYF granules twice daily. The intervention lasted for 6 months. Clinical researchers, participants and statisticians were blinded to the treatment assignment throughout the study. The primary outcomes were scores of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Montreal Cognitive Assessment (MoCA) test and Mini-Mental State Exam (MMSE). The serum levels of acetylcholinesterase (AchE) and amyloid-β protein 42 (Aβ) were detected with enzymelinked immunosorbent assay kits. The scale assessments were conducted at baseline, the 3rd and 6th months of treatment, respectively. Biochemistry tests were conducted at baseline and the 6th month of treatment.@*RESULTS@#A total of 52 patients completed the trial, 28 in HYF group and 24 in donepezil group. Compared with the baseline, HYF and donepezil signifificantly decreased the total scores of ADAS-Cog and CM-SS, and signifificantly increased the scores of MoCA and MMSE after 6-month treatment (all P<0.01). Both treatments remarkably reduced the serum levels of AchE and Aβ (both P<0.05). The CM-SS total effective rate of HYF was signifificantly higher than donepezil [75.00% (21/28) vs. 54.17% (13/24), P<0.05]. No severe adverse events were observed in both groups.@*CONCLUSION@#HYF is effective and safe for improving the cognitive function in mildto-moderate AD patients. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-IOR-17011746)].
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<p><b>OBJECTIVE</b>To observe the effects of Huannao Yicong Formula (, HYF) on learning and memory and it's regulating effect on γ-secretase related anterior pharynx defective 1 (APH-1), presenilin enhancer-2 (PEN-2) signaling pathway, so as to discuss and further clarify the mechanism of HYF on Alzheimer's disease.</p><p><b>METHODS</b>Sixty APP/PS1 transgenic mice, randomly allocated into 4 groups, the model group, the donepezil group (0.65 mg/kg), HYF low-dose group (HYF-L, 5.46 g/kg) and HYF high-dose group (HYF-H, 10.92 g/kg), 15 for each group. Another 15 C57BL/6J mice with the same age and same genetic background were allocated into the control group, proper dosage of drugs or distilled water were given by intragastric administration once daily for 12 weeks. After 12 weeks of administration, the learning and memory abilities of mice in each group was evaluated by the morris water maze test, amyloid precursor protein (APP), Aβand Aβlevels in hippocampus were detected by enzyme-linked immunosorbent assay, γ-secretase was detected by dual luciferase assaying, the levels of APH-1a, hypoxia-inducible factor 1α (HIF-1α), cAMP response element-binding protein (CREB) and PEN-2 and their mRNA expression was measured by Western blot and real-time polymerase chain reaction.</p><p><b>RESULTS</b>HYF can ameliorate learning and memory deficits in APP/PS1 transgenic mice by decreasing the escape latency, improving the number of platform crossing and swimming speed (P<0.01, P<0.05). HYF can decrease the levels of APP, Aβ, Aβand the activity of γ-secretase in hippocampus of Alzheimer's disease model mice. HYF can down-regulate the levels of CREB and PEN-2 and the expression of their mRNA.</p><p><b>CONCLUSION</b>HYF can improve the learning and memory ability by inhibiting the activity of γ-secretase through the CREB/PEN-2 signaling pathway, and this may be one of the therapeutic mechanisms of HYF in Alzheimer's disease.</p>
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Animales , Femenino , Masculino , Secretasas de la Proteína Precursora del Amiloide , Metabolismo , Precursor de Proteína beta-Amiloide , Metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Genética , Metabolismo , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Endopeptidasas , Genética , Metabolismo , Ensayo de Inmunoadsorción Enzimática , Regulación de la Expresión Génica , Hipocampo , Metabolismo , Patología , Subunidad alfa del Factor 1 Inducible por Hipoxia , Genética , Metabolismo , Inmunohistoquímica , Aprendizaje , Trastornos de la Memoria , Quimioterapia , Genética , Ratones Endogámicos C57BL , Ratones Transgénicos , Presenilina-1 , Metabolismo , Presenilina-2 , Genética , Metabolismo , ARN Mensajero , Genética , Metabolismo , Transducción de SeñalRESUMEN
<p><b>OBJECTIVE</b>Huannao Yicong Decoction (, HYD), an effective herbal formula against Alzheimer's disease (AD), has been proven to have neuroprotective action in amyloid β-protein(Aβ)-induced rat model. This study was designed to characterize mechanisms by which HYD leads to suppression of inflflammation and apoptosis in the brains of Aβ-induced rat.</p><p><b>METHODS</b>A total of 72 rats were divided into 6 groups, which were referred to as: sham operation group, model group, donepezil-treated group, HYD low-dose group (HYDL), HYD middle-dose group (HYDM) and HYD high-dose group (HYDH). Rats in HYDL, HYDM and HYDH were injected with Aβat the CA1 region of hippocampus to form AD model and were fed the HYD extract at different dose of 3.78, 7.56 and 18.90 g crude drug/kg. The behavioral changes of rats were evaluated by Morris water maze (MWM) before sacrififice. Pathological changes of the brain tissue were evaluated using hematoxylin eosin (HE) staining. The levels of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) were measured by radioimmunoassay. The levels of Aβ and proteins that are associated with apoptosis such as B-cell lymphoma-2 protein (Bcl-2), Bcl-2-associated X protein (Bax), cysteine-aspartic protease (caspase)-3, -8, -9 and -12 in serum were measured by immunohistochemistry.</p><p><b>RESULTS</b>Compared with the sham operation group, the spatial learning and memory abilities of AD rats were signifificantly decreased (P<0.05 or P<0.01; Expressions of IL-1, TNF-α, Aβ and apoptosis-signaling proteins caspase-3, -8, -9, -12 were signifificantly up-regulated (P<0.05 or P<0.01). The ratio of Bcl-2 to Bax were signifificantly decreased in the model group (P<0.01). When treated with HYD extract, the spatial learning and memory abilities of AD-model rats were significantly increased (P<0.05 or P<0.01), IL-1, TNF-α, Aβ, caspase-3, -8, -9 and -12 were down-regulated (P<0.05 or P<0.01), and the ratio of Bcl-2 to Bax were reduced (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>HYD extract can improve the learning and memory ability defificits, alleviate the inflflammatory response and pathological manifestations induced by Aβinjection in the rat model of AD. HYD down-regulates the levels of IL-1, TNF-α and Aβ, and decreases the rate of apoptosis by modulating apoptosis-signaling-related proteins such as caspase-3, -8, -9, and -12.</p>
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Objective@#To investigate the epidemic features of persistent genital chlamydial infection (GCI) in Tianjin area.@*METHODS@#We statistically analyzed the clinical data about the persistent GCI patients received at the Venereal Disease Clinic of Tianjin Medical University General Hospital from 2009 to 2011.@*RESULTS@#A total of 158 patients with persistent GCI were received from Tianjin area. The patients ranged in age from 19 to 67 years, 39.24% from 20 to 29 and 34.81% from 30 to 39 years, 36.71% with commercial occupation, and 55.06% with college education or above. The sex partners of the patients included their spouses (32.91%) and waitresses (41.77%). The incidence probability of persistent GCI was higher in the females (59.49%) than in the males. Many of the patients were complicated with infections of mycoplasma, syphilis, candida albicans, or condyloma acuminatum.@*CONCLUSIONS@#The epidemic trend of persistent GCI is rather grim in Tianjin area. New measures have to be developed targeting the epidemiological features of persistent GCI for better prevention and control of the disease.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , China , Epidemiología , Infecciones por Chlamydia , Epidemiología , Estudios Epidemiológicos , Incidencia , Factores de Riesgo , Distribución por Sexo , Parejas SexualesRESUMEN
<p><b>OBJECTIVE</b>To observe the reconstruction features of adventitia in senescent rats, and to explore the intervention mechanism of Chinese herbs (CH, extracts from Radix Ginseng, Radix Notoginseng, and Rhizoma Chuanxiong).</p><p><b>METHODS</b>Totally 85 20-month senescent rats were randomly divided into 5 groups according to body weight, i.e., the aging model group, the high dose CH group, the middle dose CH group, the low dose CH group, the Losartan group, 17 in each group. Another 14 2-month old Wistar rats were selected as a young group. Extracts of CH at the daily dose of 1493. 4, 746. 7, and 373. 4 mg/kg were administered to rats in the 3 CH groups respectively by gastrogavage. Losartan suspension at the daily dose of 10 mg/kg was administered to rats in the Losartan group by gastrogavage. Equal volume of distilled water was administered to rats in the aging model group and the young group. All medication was performed once daily. After 15-week intervention, morphological changes of thoracic aorta were observed by HE staining. The types, distribution, and contents of vessel wall collagens were determined using picric acid picrosirius red staining. The plasma renin activity (PRA) , the concentration of rennin angiotensin II (Ang II), and the content of Ang II in adventitia were detected by radioimmunoassay. The content of hydroxyproline ( Hyp) was detected by biochemical analysis. mRNA contents and protein expressions of angiotensin II receptor 1 (AT1R) and angiotensin II receptor 2 (AT2R) were detected by real-time PCR (RT-PCR) and Western blot.</p><p><b>RESULTS</b>Compared with the young group, thickened adventitia, increased adventitia thickness/caliber, accumulated collagen fiber, increased area of type I collagen, decreased area of type III collagen, decreased type III/I collagen area ratio (P <0. 05), decreased plasma PRA and Ang II (P < 0.01, P < 0.05), increased contents of Ang II and Hyp in adventitia, down-regulated mRNA and protein expressions of AT1R, and up-regulated mRNA and protein expression of AT2R could be seen in the aging model group (P < 0.05). Compared with the aging model group, morphological changes could be improved in the 3 CH groups. Adventitia thickness/caliber was reduced in middle and high dose CH groups, as well as the Losartan group. The area of type I collagen was reduced and the area of type III collagen was enlarged, type III/I collagen area ratio obviously increased, contents of adventitia Hyp was obviously lowered in the high dose CH groups and the Losartan group (P < 0.05, P < 0.01). Ang II levels in adventitia decreased in middle and high dose CH groups and the Losartan group (P < 0.05, P < 0.01). There was no statistical difference in PAR among all groups (P > 0.05). Compared with the aging model group, mRNA expression of AT1R all increased in each treatment group (P < 0.01); mRNA expression of AT2R also increased in middle and high dose CH groups (P < 0.05). Protein expression of AT1R increased in the high dose CH group and the Losartan group (P < 0.01, P < 0.05); protein expression of AT2R also increased in middle and high dose CH groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Adventitia remodeling occurred in aged rats, manifested as thickened adventitia and accumulated collagens, disordered ratios of collagen I and III. Its mechanism might be possibly associated with aactivation of renin-angiotensin system (RAS). Extracts from Radix Ginseng, Radix Notoginseng, and Rhizoma Chuanxiong could improve adventitial remodeling possibly by interfering multi-targets, such as Ang II and AT1R, thereby delaying vascular aging.</p>
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Animales , Ratas , Adventicia , Envejecimiento , Angiotensina II , Aorta Torácica , Medicamentos Herbarios Chinos , Farmacología , Losartán , Panax , Raíces de Plantas , ARN Mensajero , Ratas Wistar , Sistema Renina-Angiotensina , RizomaRESUMEN
Traditional Chinese medicine Curcuma Zedoary ( E'Zhu) contains essential oil, curcuminoid and other effective constituents, with such pharmacological actions as anti-platelet aggregation, lowing blood lipid, anti-oxidation and anti-inflammation. In recent years, studies have showed that certain extracts and chemical components of E'Zhu could mitigate myocardial cell mitochondria injury and protect vascular endothelium by enhancing heme oxygenase-1 activity, inhibit nuclear factor NF-kappaB, target genes interleukin-associated kinase-1 (IRAK-1), tumor necrosis factor receptor-6 (TRAF-6) and vascular cell adhesion molecule-1 (VCAM-1), reduce inflammatory infiltration, and inhibit growth factor-induced smooth muscle cells (SMCs) proliferation and migration by impacting oxidation of cellular phosphatases. Due to its different functions in vascular endothelial cells and smooth muscle cells, E'Zhu has been applied in drug-eluting stents, with a potential effect in preventing in-stent restenosis and thrombogenesis. In this paper, studies on pharmacological effects and mechanisms of extracts and main chemical constituents from E'Zhu in preventing vascular restenosis were summarized.
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Animales , Humanos , Constricción Patológica , Quimioterapia , Cirugía General , Curcuma , Química , Medicamentos Herbarios Chinos , Química , Farmacología , Endotelio Vascular , StentsRESUMEN
<p><b>OBJECTIVE</b>To observe blood flow features in elderly hypertension patients of different Chinese medical syndrome types and to test their correlation with rheological properties of red blood cells (RBCs) by applying micro-channel array flow analyzer (MC-FAN).</p><p><b>METHODS</b>Recruited were 109 elderly hypertension patients were assigned to phlegm-stasis blocking collateral group (35 cases), yin deficiency yang hyperactivity group (42 cases), Shen deficiency group (32 cases) according to Chinese medical syndrome typing. Besides, another 21 elderly healthy subjects were recruited as the control group. The hemorheology visualization testing of elderly hypertension patients was detected using MC-FAN. The erythrocyte deformation index (DI), erythrocyte aggregation index (EAI), and erythrocyte related plasma ATPase activity were observed. The correlation between the transiting time (TT) of blood hemorheology visualization and rheological indicators of RBCs were analyzed.</p><p><b>RESULTS</b>The hemorheology visualization TT was significantly prolonged more in the phlegm-stasis blocking collateral group than in the yin deficiency yang hyperactivity group, the Shen deficiency group, and the control group (P < 0.05). Compared with the control group, the DI was significantly lower in the phlegm-stasis blocking collateral group than in the yin deficiency yang hyperactivity group, the Shen deficiency group, and the control group (P < 0.05) when the shear rate was 100 s(-1). Compared with the control group, the plasma Na+ -K(+) -ATPase activity and the plasma Ca2+ -Mg2+ -ATPase activity were significantly lower in elderly hypertension patients (P < 0.01). Among the three groups, plasma Ca2+ -Mg2+ -ATPase activity was significantly lower in the phlegm stasis blocking collateral group than in the Shen deficiency group (P < 0. 05). The hemorheology visualization TT (10, 30, 60, and 100 microL) was negatively correlated with DI. The hemorheology visualization TT at 100 microL was positively correlated with EAI.</p><p><b>CONCLUSION</b>Changes of hemorheology visualization TT of elderly hypertension patients were significant and correlated with traditional EAI.</p>
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Agregación Eritrocitaria , Deformación Eritrocítica , Hemorreología , Hipertensión , Sangre , Diagnóstico , Medicina Tradicional China , MétodosRESUMEN
<p><b>OBJECTIVE</b>To study the effects of Huannao Yicong Recipe (HNYCR)extract on the learning and memory ability, and the expressions of amyloid precursor protein (APP), beta-site APP-cleaving enzyme 1 (BACE1), presenilin-1 (PS-1), and beta amyloid protein (Abeta)in hippocampus CA1 area of APP transgenic mice, and to explore its mechanisms for treating Alzheimer's disease (AD).</p><p><b>METHODS</b>Totally 3-month-old APP695V7171 transgenic mice were used to establish the AD model in this research. They were randomly divided into the model group, the Donepezil group, the large dose HNYCR extract group, the small dose HNYCR extract group, and the normal control group (C57BL/6J mice), 15 in each group. These animals were gavaged for 4 continuous months. Relevant indicators were detected: Morris water maze test was used to measure the spatial learning and memory ability. The immunohistochemical assay was used to detect the expressions of APP, BACE1, PS-1, and Abeta.</p><p><b>RESULTS</b>The times of crossing the original platform and the swimming time and distance in the fourth quadrant of the 7-month-old APP transgenic mice were significantly reduced in Morris water maze test, when compared with the normal control group (P < 0.01). The times of crossing original platform and the swimming time and distance in the fourth quadrant of all treatment groups significantly increased in Morris water maze test, when compared with the model group (P < 0.05). The expressions of APP, BACE1, PS-1, and Abeta in hippocampus CA1 area of 7-month-old model mice increased significantly (P < 0.01), when compared with the normal control group. The expressions of APP, BACE1, PS-1, and Abeta in each 7-month-old intervention groups were significantly reduced, when compared with the model group (P < 0.01).</p><p><b>CONCLUSION</b>Early application of HNYCR extract can obviously improve the learning and memory ability of APP transgenic mice that has declined, reduce the expressions of APP, BACE1, PS-1, and Abeta in the hippocampal CA1 area, reduce the production of Abeta, and slow down the pathological process of brains in APP transgenic mice.</p>
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Animales , Femenino , Masculino , Ratones , Enfermedad de Alzheimer , Metabolismo , Secretasas de la Proteína Precursora del Amiloide , Genética , Metabolismo , Péptidos beta-Amiloides , Genética , Metabolismo , Precursor de Proteína beta-Amiloide , Genética , Metabolismo , Ácido Aspártico Endopeptidasas , Genética , Metabolismo , Encéfalo , Metabolismo , Región CA1 Hipocampal , Metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Farmacología , Aprendizaje por Laberinto , Memoria , Ratones Endogámicos C57BL , Ratones Transgénicos , Presenilina-1 , Genética , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To examine the effect of the zedoary essential component-eluting stent (ZES) on a porcine coronary neointimal formation.</p><p><b>METHODS</b>ZES, sirolimus-eluting stents (SES), and bare metal stents (BMS) were randomly implanted in three different major epicardial vessels in 36 balloon-injured pigs. Coronary angiography, optical coherence tomography, and histomorphological analysis were used to determine antihyperplasia effects.</p><p><b>RESULTS</b>ZES and SES had a significantly larger lumen diameter and area, and reduced diameter and area of stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS (P<0.01). Histomorphometric analysis showed moderate inflammatory responses, such as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells in some arteries with SES compared with ZES (P<0.05). Injury scores were not different among the three groups at 30 and 90 days. The endothelialization score in the SES group was 2.69 ± 0.42 at 30 days and 2.83 ± 0.39 at 90 days compared with the ZES and BMS groups (both were 3.00 ± 0.00 at either 30 or 90 days, P<0.05). Well developed endothelium was observed in the ZES group, while incomplete endothelium and inflammatory cells were observed with stent struts partly naked at the vessel lumen in the SES group.</p><p><b>CONCLUSION</b>The ZES inhibits neointimal hyperplasia with good endothelia coverage in the porcine balloon injury coronary model.</p>
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Animales , Materiales Biocompatibles Revestidos , Farmacología , Estenosis Coronaria , Patología , Vasos Coronarios , Patología , Curcuma , Química , Endotelio Vascular , Patología , Inflamación , Patología , Microscopía Electrónica de Rastreo , Neointima , Patología , Implantación de Prótesis , Stents , Sus scrofa , Factores de TiempoRESUMEN
<p><b>OBJECTIVE</b>To study the distribution characteristics and the targeting feature of polyethylene glycol (PEG) modified 5-fluorouracil magnetic albumin microspheres (5-FU-MAMS) and 5-FU-MAMS in major organs of colorectal neoplasm nude mice under magnetic field, and to provide experimental evidence for targeting therapy.</p><p><b>METHODS</b>Eighteen mice were equally divided into PEG-5-FU-MAMS group(n=6), 5-FU-MAMS group(n=6), and 5-FU group(n=6). The colorectal neoplasm was exposed in the magnetic field of 3000 GS for 30 minutes. Three types of 5-FU were injected through the vena caudalis at the dose of 8 mg/kg. Thirty minutes later, the animals were immediately sacrificed after blood draw from the fossa orbitalis. The concentration of 5-FU in different organs including liver, lung, and tumor tissue were determined by the high performance liquid chromatography (HPLC).</p><p><b>RESULTS</b>The 5-FU concentrations in colorectal cancer tissue, liver, lung, and blood were(73.3±3.2), (22.1±2.7), (26.3±2.8), and(1.6±0.6) mg/L in the PEG-5-FU-MAMS group, and were(55.9±5.4), (46.3±8.2), (39.4±5.4), and(1.7±0.4) mg/L in the 5-FU-MAMS group. The 5-FU concentration in colorectal neoplasm was higher in the PEG-5-FU-MAMS group than that in the 5-FU-MAMS group(P<0.01), while the concentration was lower in the liver and the lung than that in the 5-FU-MAMS group(all P<0.01). There were no significant difference of 5-FU concentration in the blood sample(P>0.05).</p><p><b>CONCLUSION</b>Both PEG-5-FU-MAMS and 5-FU-MAMS show significant magnetic targeting to the colorectal neoplasm, and passive target capacity of PEG-5-FU-MAMS to liver and the lung. PEG modification can decrease passive target capacity and the active target capacity can be enhanced, which efficiently reduces the toxicity of chemotherapeutic agents to important organs, and therefore provides a new initiative targeting chemotherapy for cancer.</p>
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Animales , Humanos , Ratones , Neoplasias Colorrectales , Quimioterapia , Metabolismo , Fluorouracilo , Farmacocinética , Magnetismo , Ratones Desnudos , Microesferas , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
<p><b>OBJECTIVE</b>To study the effects of Huannao Yicong formula (HNYCF) extract on behavior and ultrastructure of mitochondria in hippocampus CA1 area of APP transgenic mice of different months, and explore its partial mechanism in treating Alzheimer's disease (AD) through the perspective of energy metabolism.</p><p><b>METHOD</b>One hundred and twenty APP695V717I transgenic mice of 3-month old were divided randomly into model group, Donepezil group (0.65 x 10(-3) g x kg(-1) x d(-1)), HNYCF extract large dose group (2.8 g x kg(-1) x d(-1)) and HNYCF extract small dose group (1.4 g x kg(-1) x d(-1)), and 30 mice in each group. Another 30 C57BL/6J mice with the same age and background were used as normal control group. All animals were administered once daily by gavage with the corresponding drug or distilled water. The course of intervention was 4 and 6 months. Behavioral changes were observed by Morris water maze test and step down test. Ultrastructure of mitochondria in hippocampus CA1 area was observed by transmission electron microscope.</p><p><b>RESULT</b>At the age of 7 and 9 month, the number of times of passing through platform, swimming time and path length of model group increased significantly (P < 0.05, P < 0.01) in Morris water maze test, and the latent period decreased (P < 0.01) in step down test compared with normal group, and it would get worse with the development of disease course. HNYCF extract could increase the number of times of passing through platform, swimming time and path length (P < 0.05, P < 0.01) in Morris water maze test, prolong latent period in step down test of different age. At the age of 7 and 9 month, mitochondrial of hippocampus CA1 area was disrupted and dissolved. Most ridge structure arranged in a mess, and some ridge showed expanding, matrix loosing and swollen appearance, and it would get worse with the development of disease course. HNYCF extract could improve ultrastructure of mitochondria in hippocampus CA1 area, and increase its quality.</p><p><b>CONCLUSION</b>Learning and memory ability decreased in APP transgenic mice model, and the quantity of neural mitochondria in hippocampus CA1 area with structure disrupting, and it would get worse with the development of disease course. HNYCF extract could improve the learning and memory ability of APP transgenic mice model, its mechanism might relate with improving ultrastructure of mitochondria in hippocampus, and increasing its quantity.</p>
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Animales , Femenino , Masculino , Ratones , Factores de Edad , Enfermedad de Alzheimer , Quimioterapia , Patología , Conducta Animal , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Farmacología , Hipocampo , Aprendizaje por Laberinto , Medicina Tradicional China , Memoria , Ratones Endogámicos C57BL , Ratones Transgénicos , Mitocondrias , Distribución Aleatoria , Organismos Libres de Patógenos EspecíficosRESUMEN
<p><b>OBJECTIVE</b>To observe the effect of Huannao Yicong Prescription (, HNYC, a Chinese medical compound) extract on β-amyloid precursor protein (APP) metabolic signal transduction related protein kinase C (PKC), tyrosine amyloid protein kinase (TrKA), and glycogen synthase kinase-3 (GSK-3) in brain tissue of transgenic mouse dementia model induced by APP.</p><p><b>METHODS</b>Sixty dementia model transgenic 3-month-old mice induced by APP695V717I were randomly allocated in four groups: the model group (A), the Donepezil (0.65×10(-3) g·kg(-1)·(-1))-treated group (B), and the two HNYC-treated groups (C and D) with high dosage (2.8 g·kg(-1)·(-1)) and low dosage (1.4 g·kg(-1)·(-1)) of HNYC extract, respectively, 15 mice in each group. Besides, a normal control group was set up with 15 C57BL/6J mice with the same age and genetic background as the model mice. The drugs for treatment were administered once a day by dissolving in equal-volume distilled water through gastric infusion, continued for 6 months, to mice in group A and to normal control group equal-volume distilled water was administered instead. Spatial learning and memory capacity of mice were observed by Morris water maze; their one-time escape response memory capacity was tested by diving platform; and changes of PKC, TrkA, and GSK-3 levels in hippocampus and cortex of brain were detected by Western blotting.</p><p><b>RESULTS</b>HNYC extract showed significant effects on increasing the time of model mice for swimming through the flat roof and the swimming time and path in the fourth quadrant P<0.05 or P<0.01). Diving platform test showed that the latent times in Groups B and C were longer than that in Group A significantly (P <0.05 and P<0.01). Compared with the normal control group, PKC and TrkA protein expression levels in hippocampus and cortex of model mice's brain lowered significantly (P<0.01), while GSK-3 protein expression increased significantly (P<0.01); compared with Group A (the model group), hippocampal and cortical levels of PKC protein expression in the intervened groups (B-D) as well as those of TrkA in Group C were higher (P<0.01 or P<0.05), while hippocampal levels of GSK-3 in intervened groups were lower (P<0.01).</p><p><b>CONCLUSION</b>HNYC extract could obviously increase the protein expressions of PKC and TrkA and decrease the expression of GSK-3 protein in brain tissue of transgenetic mice model of dementia, and regulate APP metabolic signal transduction path, and thus to suppress the production of Aβ, which is one of the dominant mechanisms for improving learning/memory capacity of dementia model animals.</p>
Asunto(s)
Animales , Femenino , Masculino , Ratones , Precursor de Proteína beta-Amiloide , Metabolismo , Encéfalo , Metabolismo , Patología , Cromatografía Líquida de Alta Presión , Demencia , Metabolismo , Patología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Farmacología , Glucógeno Sintasa Quinasa 3 , Metabolismo , Hipocampo , Metabolismo , Patología , Memoria , Ratones Endogámicos C57BL , Ratones Transgénicos , Extractos Vegetales , Farmacología , Proteína Quinasa C , Metabolismo , Receptor trkA , Metabolismo , Transducción de SeñalRESUMEN
<p><b>OBJECTIVE</b>To evaluate the clinical effects of Chinese medicine (CM) on acute myocardial infarction (AMI) with a prospective cohort study.</p><p><b>METHODS</b>A total of 334 AMI patients from January 2007 to March 2009 were consecutively enrolled, and were assigned to a treatment group (169 cases) treated with combined therapy (CM for at least one month and Western medicine) and a control group (165 cases) with Western medicine alone. Clinical data including age, gender, smoking, medical history, infarction area, heart functional classification, CM syndrome scores, blood-stasis syndrome score, primary end-point (death, nonfatal myocardial infarction, and revascularization) and secondary end-point (ischemic stroke, rehospitalization due to angina, heart failure and shock), were collected. CM syndrome scores, blood-stasis syndrome score, primary end-point and secondary end-point were collected during the 6-month follow-up. Kaplan-Meier method was used for the survival analysis. The multifactor analysis was analyzed by Cox proportional hazards regression.</p><p><b>RESULTS</b>At the end of 6-month the CM syndrome score and bloodstasis syndrome score in the treatment group were lower than those in the control group (P<0.01), especially the symptoms of chest pain, spontaneous perspiration and insomnia. Rehospitalization rate due to angina during the 6-month follow-up in the treatment group (2.96%) was lower than that in the control group (7.88%, P<0.05). Kaplan- Meier survival curve showed that event-free cumulated survival of rehospitalization due to angina during the 6-month follow-up in the treatment group was higher than that in the control group (Log rank 4.700, P=0.03). Cox regression analysis showed that heart dysfunction [hazard ratio (HR)=1.601, 95% CI=1.084-2.364, P=0.018] and diabetes mellitus (HR=1.755, 95% CI=1.031-2.989, P=0.038) were hazard factors to end-point, whereas CM (HR 0.405, 95% CI=0.231-0.712, P=0.002), percutaneous coronary intervention (PCI, HR=0.352, 95% CI=0.204-0.607, P<0.001) and angiotensin converting enzyme (ACE) inhibitors (HR=0.541, 95% CI=0.313-0.936, P=0.028) were protective factors.</p><p><b>CONCLUSIONS</b>CM therapy could decrease CM syndrome scores and blood-stasis syndrome score, reduce the rehospitalization rate during 6-month follow-up due to angina. Heart dysfunction and diabetes mellitus were hazard factors to end-point, whereas CM, PCI and ACE inhibitors were protective factors.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Estudios de Cohortes , Enfermedades Hematológicas , Epidemiología , Hospitalización , Medicina Tradicional China , Métodos , Infarto del Miocardio , Epidemiología , Terapéutica , Estudios Prospectivos , Proyectos de Investigación , Síndrome , Resultado del TratamientoRESUMEN
<p><b>OBJECTIVE</b>To observe the effect of early intervention using extract of Huannao Yicong Decoction (, HYD) on the pathological picture of hippocampus, neurocyte apoptosis, and associated regulatory genes in β-amyloid precursor protein (APP) transgenic mice model of dementia.</p><p><b>METHODS</b>Sixty APP695(V7171) transgenic mice were randomly divided into four groups of 15. The model group was treated with distilled water, the positive control group was treated with donepezil (0.65 mg/kg), and the two HYD groups were treated with high dose (2.8 g/kg) and low dose (1.4 g/kg) HYD, respectively. All testing drugs were administered through gastrogavage by dissolving in equal volume of distilled water, once a day for six successive months. In addition, a normal control group with 15 healthy C57BL/6J mice of the same age and genetic background was set up with distilled water treatment. The pathologic picture of brain tissue was observed by microscopy with HE stain; the amount of apoptosis cells in the hippocampal CA1 area was detected by TUNEL; and expressions of associated genes, Bcl-2, and Bax were determined by immunohistochemical method.</p><p><b>RESULTS</b>Pathologic pictures of hippocampus showed that in the model group, cells messily arranged, neurons markedly decreased, and the surrounding tissue of some cells was loosened with edema, necrosis, and widened gap with glia cells proliferation. Compared with those in the normal group, the amount of apoptosis cells in the CA1 area was increased, Bcl-2 expression decreased, and Bax expression increased significantly, with markedly reduced Bcl-2/Bax ratio in the model group. Compared to the model group, the pathological changes were significantly milder in the HYD-treated groups, showing rather regularly arranged cells, significantly increased neurons, only few denatured necrotic cells with milder edema, less proliferation of glia cells, and obviously reduced cell apoptosis in CA1 area (P<0.05 or P<0.01). Besides, Bcl-2 expression was up-regulated and Bax expression down-regulated, and Bcl-2/Bax ratio significantly increased in the two HYD groups (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Early intervention with HYD could improve the abnormal pathologic picture of hippocampus and regulate the expressions of associated genes to suppress cell apoptosis, which might be its mechanism of action in alleviating cognitive functional disorder.</p>
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Animales , Humanos , Ratones , Precursor de Proteína beta-Amiloide , Genética , Apoptosis , Demencia , Quimioterapia , Patología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Hipocampo , Patología , Inmunohistoquímica , Ratones Endogámicos C57BL , Ratones Transgénicos , Neuronas , Patología , Extractos Vegetales , Farmacología , Usos Terapéuticos , Proteína X Asociada a bcl-2 , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate effect of Xiongshao Capsule (XSC) combined with ischemic postconditioning (IPoC) on tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) contents as well as inflammatory cell infiltration (ICI) in myocardium of rat with ischemic reperfusion (I/R) injury.</p><p><b>METHODS</b>Seventy-five Sprague-Dawley rats were equally randomized into 5 groups, the sham-operated group (A), the I/R group (B), the IPoC group (C), the fosinopril sodium plus IPoC group (D), and the XSC plus IPoC group (E). Excepting rats in Group A, all animals received I/R injury through a 30-min occlusion of left anterior descending artery followed by 1-h reperfusion. Additionally, IPoC (3 cycles of 10 s reperfusion/10 s of ischemia) was applied on rats in Group C before 1 h of reperfusion; while rats in Groups D and E were pretreated for 14 days with 0.9 mg/kg fosinopril sodium and 0.135 g/kg XSC respectively via gastrogavage, and the I/R injury with IPoC applied 2 h after the final gavage. Serum creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) levels were detected by colorimetric method, myocardial infarction size was measured by nitro blue tetrazolium chloride (NBT) staining, MCP-1 and TNF-alpha contents in myocardial tissue were examined by enzyme-linked immunosorbent assay (ELISA), and ICI was detected by HE staining.</p><p><b>RESULTS</b>Compared with Group B, myocardial enzymes and infarction size were significantly decreased (P<0.01), contents of MCP-1, TNF-alpha and ICI in myocardial tissue were significantly decreased (P<0.05, P<0.01) in Group C. Compared with Group C, further reduced infarction size and release of myocardial enzyme CK-MB (P<0.01) were seen in Group E, and contents of MCP-1 and TNF-alpha as well as ICI in myocardial tissue in Group E were also significantly lower (P<0.05, P<0.01).</p><p><b>CONCLUSION</b>XSC could enhance the protective effect of IPoC on rat with myocardial I/R injury, and the mechanism may be related to its inhibition on MCP-1 and TNF-alpha expressions as well as ICI suppression.</p>
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Animales , Femenino , Masculino , Ratas , Quimiocina CCL2 , Metabolismo , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Poscondicionamiento Isquémico , Métodos , Isquemia Miocárdica , Daño por Reperfusión Miocárdica , Metabolismo , Miocardio , Metabolismo , Fitoterapia , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the effects of fosinopril sodium pre-treatment combined with ischemic postconditioning on rat serum and myocardial oxidative stress and proinflammatory cytokines post ischemia/reperfusion.</p><p><b>METHODS</b>Sixty Sprague-Dawley rats were randomly divided into sham group (n = 15), ischemia/reperfusion group (30 minutes in situ occlusion of the left anterior descending artery followed by 1 hour reperfusion, n = 15), IPoC group (30 minutes occlusion of the left anterior descending artery followed by 3 cycles of 10 seconds of reperfusion/10 seconds of ischemia before 1 hour reperfusion, n = 15) and fosinopril sodium group [pretreated with fosinopril sodium (0.9 mg×kg(-1)×d(-1) for 14 days) followed by IPoC protocol at 2 h after the last gavage, n = 15]. The arterial blood and heart samples were extracted after 1 hour reperfusion. Serum CK-MB and cTnT levels were detected by colorimetric method, myocardial infarction size was measured by nitrotetrazolium blue chloride staining, SOD content was examined by colorimetric method, MDA content was detected using thiobarbituric acid method, serum levels of Interleukin-1α (IL-1α), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were examined by radioimmunoassay, IL-1α, IL-6 and TNF-α levels of myocardial tissue were detected by ELISA.</p><p><b>RESULTS</b>Compared with I/R group, myocardial enzymes and infarction size were significantly decreased (P < 0.05, P < 0.01), serum SOD content was increased and MDA content was decreased (all P < 0.01), serum and myocardial levels of IL-1α, IL-6 and TNF-α were significantly reduced (P < 0.05, P < 0.05, P < 0.01) in IPoC group. Compared with IPoC group, fosinopril sodium pretreatment further reduced infarction size and myocardial enzyme CK-MB (P < 0.05), increased SOD content (P < 0.05) while reduced serum IL-6 and myocardial tissue TNF-α (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Pretreatment with fosinopril sodium enhanced the protective effect of IPoC on rat myocardium underwent I/R injury, possibly by reducing oxidative stress and early inflammatory reaction.</p>
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Animales , Ratas , Forma MB de la Creatina-Quinasa , Sangre , Fosinopril , Usos Terapéuticos , Interleucina-1alfa , Sangre , Interleucina-6 , Sangre , Precondicionamiento Isquémico Miocárdico , Métodos , Malondialdehído , Sangre , Daño por Reperfusión Miocárdica , Metabolismo , Patología , Miocardio , Metabolismo , Patología , Ratas Sprague-Dawley , Superóxido Dismutasa , Sangre , Troponina T , Sangre , Factor de Necrosis Tumoral alfa , SangreRESUMEN
<p><b>OBJECTIVE</b>To observe the effect of Chinese medical regimen and integrative medical regimen on quality of life and early renal impairment in elderly patients with isolated systolic hypertension (EISH).</p><p><b>METHODS</b>A multi-center, randomized, double-blinded controlled trail was adopted. A total of 270 cases of EISH were randomly divided into 3 groups: Chinese medicine group (CM), combination group and Western medicine group (WM). The course of treatment was 4 weeks. The clinical blood pressure, integral of quality of life (SF-36 scale), immunoglubin G (IgG), microalbumin (mALB), beta(2)-microglobulin (beta(2)-MG), transferrin (TRF) and N-acetyl-beta'-D-glucosa-minidase (NAG) in urine were determined before and after the treatment.</p><p><b>RESULTS</b>After treatment, systolic blood pressure depressed significantly in each group (P<0.05), and the combination group was superior to CM or WM group in depressing SBP (P<0.05); in each group, integral of quality of life improved in different degree, and combination group was superior to WM group in all 8 dimensions (P<0.05). The level of mALB and beta(2)-MG in urine decreased in all groups (P<0.05), and the combination group was superior to CM group or WM group in decreasing mALB (P<0.05).</p><p><b>CONCLUSIONS</b>Chinese medical regimen has affirmative effect in treating EISH patients, and could lower the systolic blood pressure, improve quality of life and early renal impairment of the patients, and integrative medical regimen has superiority on account of cooperation, and deserves further study.</p>
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Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Antihipertensivos , Farmacología , Usos Terapéuticos , Presión Sanguínea , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Hipertensión , Quimioterapia , Medicina Integrativa , Riñón , Patología , Calidad de Vida , Sístole , FisiologíaRESUMEN
<p><b>OBJECTIVE</b>To determine the expression of osteopontin (OPN) and survivin in prostate cancer tissue, and study their correlation and roles in tumor invasion and metastasis.</p><p><b>METHODS</b>The expressions of OPN and survivin in prostate cancer tissue, prostate hyperplasia tissue and normal prostate tissue were determined by RT-PCR and immunohistochemistry.</p><p><b>RESULTS</b>The positive expression rates of OPN mRNA and protein in prostate cancer tissue [76.1% (35/46) and 69.6% (32/46)] were significantly correlated to survivin expression [67.4% (31/46) and 67.4% (31/46)] (P<0.05). The expressions of OPN and survivin were related to the tumor grade and clinical stages (P<0.05). OPN and survivin were not found in prostate hyperplasia and normal prostate tissues.</p><p><b>CONCLUSION</b>OPN and survivin may play important roles in the progression of prostate cancer and can be potential markers for invasion and metastasis of prostate cancer. OPN and survivin might play synergetic roles in prostate carcinogenesis.</p>