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Objective:To observe the expression of hepatocyte nuclear factor 1<italic>α</italic> (HNF1<italic>α</italic>), proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein cholesterol (LDLR) in hypercholesterolemia rat liver, and investigate the mechanism of Shuangyu Tiaozhi Decoction regulating cholesterol metabolism and attenuating hypercholesterolemia. Method:After providing a high-fat diet for 4 weeks, 40 SD rats were selected, 8 of which were randomly selected as normal group and fed a normal diet, and the remaining 32 rats were fed a high-fat diet. The rats successfully established as hypercholesterolemic model, were randomized into 4 groups: model group, low dose of Shuangyu Tiaozhi decoction group (7.8 g·kg<sup>-1</sup>), high dose of Shuangyu Tiaozhi decoction group (15.6 g·kg<sup>-1</sup>), and simvastatin group (4 mg·kg<sup>-1</sup>), with 8 rats in each group. The drugs were continuously given for 8 weeks. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were measured. The pathomorphological changes in liver were observed by hematoxylin and eosin (HE) staining. The immunohistochemistry was used to detect PCSK9 and LDLR expression in liver. The mRNA and protein expression levels of HNF1<italic>α</italic>, PCSK9 and LDLR were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. Result:Compared with normal group, the TC, TG, LDL-C levels in model group were significantly increased (<italic>P</italic><0.01), the morphology showed obvious liver steatosis. The mRNA and protein expression of HNF1<italic>α</italic> and PCSK9 were increased (<italic>P</italic><0.05), the mRNA and protein expression of LDLR was decreased (<italic>P</italic><0.05). Compared with model group, the serum TC, TG, LDL-C levels were significantly lowered in the Shuangyu Tiaozhi decoction high-dose group (<italic>P</italic><0.01), the serum TC, LDL-C levels were significantly lowered in the Shuangyu Tiaozhi decoction low-dose group and simvastatin group (<italic>P</italic><0.05,<italic>P</italic><0.01), while no significant effect was observed on the serum HDL-C levels in each treatment group. The liver steatosis decreased in each treatment group. The mRNA and protein expression of HNF1<italic>α</italic> was obviously decreased in each treatment group (<italic>P</italic><0.05,<italic>P</italic><0.01), the mRNA and protein expression of PCSK9 was obviously decreased in Shuangyu Tiaozhi decoction low and high-dose groups (<italic>P</italic><0.05,<italic>P</italic><0.01), the mRNA expression of PCSK9 was significantly increased in the simvastatin group (<italic>P</italic><0.01), while the protein expression showed a downward trend. The LDLR mRNA levels were significantly increased in each treatment group (<italic>P</italic><0.01), the LDLR protein expression was significantly increased in Shuangyu Tiaozhi high-dose group (<italic>P</italic><0.01), and showed an upward trend in Shuangyu Tiaozhi low-dose group and simvastatin group. Results of immunohistochemistry showed PCSK9 expression was weakly positive, the expression of LDLR was strongly positive in each treatment group. The therapeutic effect of Shuangyu Tiaozhi decoction high-dose group was more remarkable than simvastatin group, while there was no obvious difference between the Shuangyu Tiaozhi decoction low-dose group and simvastatin group. Conclusion:Shuangyu Tiaozhi decoction may reduce the blood lipid levels through HNF1<italic>α</italic>/PCSK9/LDLR signaling pathway, play an active role on regulating cholesterol metabolism and alleviating high-fat diet-induced hypercholesterolemia.
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Objective:To predict the therapeutic targets and related signaling pathways of quercetin in the treatment of heart failure (HF) by network pharmacology and molecular docking methods,and further clarify its mechanisms through <italic>in vitro</italic> cell model. Method:The pharmacological targets of quercetin were obtained by SwissTargetPrediction and Targetnet databases; the heart failure related targets were obtained by Online Mendelian Inheritance in Man(OMIM),GeneCards and Therapeutic Target Database(TTD) databases; the protein-protein interaction(PPI) network was analyzed by STRING database(Search Tool for Recurring Instances of Neighbouring Genes),and the PPI network diagram of quercetin for heart failure target was established. Cytoscape 3.7.2 software was used for analyzing and screening the anti-heart failure network nodes of quercetin,and the obtained targets were enriched with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis by DAVID database. In order to explore the mechanism of quercetin in the treatment of heart failure,we used cell model to verify the function in heart failure treatment. Results:The predicted results showed that there were 23 targets for the treatment of heart failure,such as Matrix Metallopeptidase-9(MMP-9),androgen receptor(AR),coagulation factor 2(F2),insulin like growth factor 1 receptor(IGF1R),epidermal growth factor receptor(EGFR),janus kinase-2(JAK2),cytochrome P450 family 19 subfamily A member 1(CYP19A1),estrogen receptor-1(ESR1),tumor necrosis factor(TNF),protein tyrosine phosphatase receptor type C(PTPRC) and cytochrome P450 family 17 subfamily A member 1(CYP17A1) etc. The results suggest that quercetin may play a role in the treatment of heart failure by intervening in the physiological processes of cardiovascular cell proliferation and metabolism,regulating hypoxia-inducible factor 1 (HIF-1)signaling pathway and steroid hormone biosynthesis. Conclusion:Quercetin has the characteristics of multi-target,multi-channel and multi-channel in the treatment of heart failure. It may play a role in the treatment of heart failure by regulating MMP-9,EGFR and other key genes,participating in the biological process of cardiac and vascular cell proliferation and metabolism.
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To investigate the effect of flavonoid compounds on vascular endothelial cells. Vascular endothelial cells were located between plasma and vascular tissue, and can complete the metabolic exchange of plasma and interstitial fluid, synthesize and secrete a variety of biologically active substances, so as to ensure the normal contraction and relaxation of blood vessels, and maintain the tension of blood vessels. Besides, it can regulate blood pressure and the balance of blood coagulation and anticoagulation, and maintain normal blood flow and long-term patency of blood vessels. Endothelial cell damage can cause a series of cardiovascular diseases, such as hypertension and coronary heart disease. Flavonoids are widely found in nature. Because these compounds are mostly yellow or light yellow, they contain ketone groups in the molecule, which are called flavones. Flavonoids are widely distributed, mostly in higher plants and ferns. Various flavonoid compounds, such as flavonoids, flavonols, flavanones isoflavones and flavanones, can protect vascular endothelial cells. This article reviews relevant findings published in domestic and foreign journals. It is found that flavonoids have effects in resisting inflammation, reducing blood vessel fragility, improving blood vessel permeability, lowering blood lipids and cholesterol, vasodilating and resisting hemagglutinating, with the same effect as phytoestrogens. They can reduce vascular endothelial cell damage through anti-inflammatory, anti-oxidative stress, stable mitochondrial function, and regulating nitric oxide(NO). It can be used in clinic to treat diseases, such as insufficient cerebral blood supply, sequelae caused by cerebral hemorrhage, hyperviscosity, cerebral thrombosis, coronary heart disease and angina pectoris.
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Flavonoids are important active ingredients of traditional Chinese medicine, mainly with cardiovascular, anti-liver injury, antioxidant, antispasmodic, and estrogen-like effects. These compounds have obvious effects on the cardiovascular and cerebrovascular diseases. Macrophage-derived foam cells are the key medium in the process of atherosclerosis(AS). In plaque, allserum lipids, serum lipoproteins, and various pro-or anti-inflammatory stimulating factors, chemokines, and small bioactive molecules can significantly affect the macrophage phenotype and induce stronger pro-inflammatory or anti-inflammatory properties. Studies have shown that some flavonoids can be used for macrophages through different pathways and mechanisms, playing an anti-atherosclerosis effect to different degrees, including promotion of cholesterol efflux from macrophages, anti-foaming of macrophages, inhibition of secretion of inflammatory factors, and antioxidant modified low density lipoprotein(ox-LDL)-induced apoptosis of macrophages. Related gene regulation inclu-ded ATP-binding cassette transporter A1(ABCA1), ATP-binding cassette transporter G1(ABCG1), Toll-like receptor(TLR), and scavenger receptor(SR). In this article, we would review the recent research progress of flavonoids on anti-atherosclerosis effect me-diated by macrophage. It is expected to provide new treatment strategies for AS-related cardiovascular and cerebrovascular diseases, and provide research ideas and development directions for the use of related natural medicines and design of new products.
Subject(s)
Humans , ATP Binding Cassette Transporter 1 , Atherosclerosis , Cholesterol , Flavonoids , Foam Cells , Lipoproteins, LDL , MacrophagesABSTRACT
Araliaceae plant Notoginseng Radix et Rhizoma, Ginseng Radix et Rhizoma and Panacix Quinquefolii Radix are famous Chinese herbal medicines, with anti-inflammatory and anti-aging effect, as well as obvious effect on cardiovascular and cerebrovascular systems. Studies have found that the metabolism and transport of cholesterol may affect the function of the cardiovascular system. Cholesterol can be divided into high-density cholesterol and low-density cholesterol. Cholesterol has many physiological regulating effect. High-density cholesterol has a protective effect on cardiovascular disease. When the cholesterol metabolism in the body is disordered, low-density cholesterol is increased, and will cause the increase in the risk of cardiovascular and cerebrovascular diseases. By consulting relevant Chinese and foreign documents and materials, we found that traditional Chinese medicine Araliaceae has a significant regulatory effect on cholesterol. It can directly regulate the cholesterol level of experimental hyperlipidemia rats, reduce total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C) in rats, and partially increase high-density lipoprotein cholesterol(HDL-C) level in rats. It can inhibit cholesterol synthesis by inhibiting cholesterol synthesis-regulating genes liver X receptor-α(LXR-α), peroxisome proliferator-activated receptor γ(PPARγ), cytochrome P450 7A1(CYP7A1); and up-regulate cholesterol metabolism genes peroxisome proliferator-activated receptor-α(PPARα), PPARγ, CYP8B1, CYP7A1, LXR) and body ATP-binding cassette transporter, ABC transporter(ABCA1, ABCG5/8)to promote cholesterol metabolism in the body. Araliaceae plants may play a neuroprotective role by regulating cholesterol metabolism and transport in the brain, and improve neurodegenerative diseases. Studies on the effect of Araliaceae plants on the metabolism and transport of cholesterol in brain will become a hot research topic in the future. The above review is expected to provide a reference for further research on the lipid-lowering effect and mechanism of Araliaceae plants.
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<p><b>BACKGROUND</b>Leukemia inhibitory factor (LIF) has been reported to possess various pharmacological effects, including displaying vascular and neuroprotective properties, during retinal disease. The aim of this study was to investigate the vascular and structural changes in the retina of diabetic mice and to explore whether LIF prevents experimental diabetes-induced retinal injury in the early stages.</p><p><b>METHODS</b>Diabetes was induced in C57Bl/6J mice with streptozotocin (STZ) injections. Successful diabetic animal models were randomly separated into two groups: the diabetic group (n = 15) and the LIF-treated group (n = 15). Normal C57BL/6 mice served as the normal control group (n = 14). Recombinant human LIF was intravitreally injected 8 weeks after the diabetic model was successfully established. Retinas were collected and evaluated using histological and immunohistochemical techniques, and flat-mounted retinas and Western blotting were performed at 18 weeks after the induction of diabetes and 2 days after the intravitreal injection of LIF. The analysis of variance test were used.</p><p><b>RESULTS</b>Histological analysis showed that there were fewer retinal ganglion cells (RGCs) and the inner nuclear layer (INL) became thinner in the diabetic model group (RGC 21.8 ± 4.0 and INL 120.2 ± 4.6 μm) compared with the normal control group (RGC 29.0 ± 6.7, t = -3.02, P = 0.007; INL 150.7 ± 10.6 μm, t = -8.88, P < 0.001, respectively). After LIF treatment, the number of RGCs (26.9 ± 5.3) was significantly increased (t = 3.39, P = 0.030) and the INL (134.5 ± 14.2 μm) was thicker compared to the diabetic group (t = 2.75, P = 0.013). In the anti-Brn-3a-labeled retinas, the number of RGCs in the LIF-treated group (3926.0 ± 143.9) was obviously increased compared to the diabetic group (3507.7 ± 286.1, t = 2.38, P = 0.030), while no significance was found between the LIF-treated group and the control group (4188.3 ± 114.7, t = -2.47, P = 0.069). Flat-mounted retinas demonstrated that a disorganized, dense distribution of the vessel was prominent in the diabetic model group. Vessel distribution in the LIF-treated mouse group was typical and the thickness was uniform. The levels of phosphosignal transducer and activator of transcription 3 activation were obviously higher in the LIF-injected retinas than those in the diabetic control group (t = 3.85, P = 0.019) and the normal control (t = -3.20, P = 0.019).</p><p><b>CONCLUSION</b>The present study provides evidence that LIF treatment protects the integrity of the vasculature and prevents retinal injury in the early stages of diabetic retinopathy in STZ-induced diabetic models.</p>
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This study focuses on the protective effect of germacrone on human umbilical vein endothelial cells(HUVECs) damaged by H2O2-induced oxidative stress and its possible mechanisms. The oxidative damage model was established by using 500 μmol•L⁻¹ H2O2 to treat HUVECs for 3 hours, and then protected with different concentrations of germacrone for 24 hours. The effect of germacrone on cell viability of HUVECs damaged by H2O2 was detected by MTT. The contents of PGI2, TXB2, ET-1, t-PA, PAI-1, TNF-α and IL-6 were detected by ELISA. The content of NO was detected by using nitrate reductase method. Colorimetry was used to detect NOS and GSH-Px. The contents of MDA, SOD and LDH were detected by TBA, WST-1 and microplate respectively. Apoptosis was observed by Hoechst 33258 fluorescent staining. The mRNA expressions of Bax, Bcl-2 and Caspase-3 in cells were detected by RT-PCR. The results showed that the cell damage rate was 52% after treated with 500 μmol•L⁻¹ H2O2 for 3 hours. The cell activity was increasing with the rise of germacrone concentration within the range of 20-200 mol•L⁻¹. Compared with normal group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were lower after damaged with H2O2. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were increased. Compared with model group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were increased after treated with germacrone. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were lower after treated with germacrone. According to Hoechst 33258 fluorescence staining, compared with normal group, the cell membrane and the nucleus showed strong dense blue fluorescence, and the number of cells significantly decreased in model group. Compared with model group, blue fluorescence intensity decreased in drug group. The above findings demonstrate that germacrone may improve the effect on HUVECs damaged by H2O2-induced oxidative stress by resisting oxidation and inhibiting cell apoptosis.
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<p><b>OBJECTIVE</b>To identify the possible association between C(-106)T polymorphism of the aldose reductase (ALR) gene and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM).</p><p><b>METHODS</b>From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy (DWR) group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C(-106)T polymorphism (rs759853) in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed.</p><p><b>RESULTS</b>A total of 268 T2DM patients (129 in the DR group and 139 in the DWR group) were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset (P=0.10) and gender (P=0.78). The success rate of genotyping for the study subjects was 99.6% (267/268), with one case of failure in the DR group. The frequencies of the T allele in the C(-106)T polymorphism were 16.0% (41/256) in the DR group and 19.4% (54/278) in the DWR group (P=0.36). There was no significant difference in the C(-106)T genotypes between the 2 groups (P=0.40). Compared with the wild-type genotype, odds ratio (OR) for the risk of DR was 0.7 (95% CI, 0.38-1.3) for the heterozygous CT genotype and 0.76 (95% CI, 0.18-3.25) for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria (OR=4.61; 95% CI, 2.34-9.05) and insulin therapy (OR=3.43; 95% CI, 1.94-6.09).</p><p><b>CONCLUSIONS</b>Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C(-106)T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.</p>
Subject(s)
Female , Humans , Male , Albuminuria , Epidemiology , Urine , Aldehyde Reductase , Genetics , Asian People , China , Cohort Studies , Diabetes Mellitus, Type 2 , Drug Therapy , Ethnology , Genetics , Diabetic Retinopathy , Drug Therapy , Ethnology , Genetics , Gene Frequency , Hypoglycemic Agents , Therapeutic Uses , Insulin , Therapeutic Uses , Logistic Models , Multivariate Analysis , Polymorphism, Single Nucleotide , RiskABSTRACT
Xuefu Zhuyu decoction (XFZYD) is a famous traditional Chinese medicine (TCM) formula, is widely used in the treatment of cardiovascular and cerebrovascular diseases in China over one hundred years. But its effect on antioxidant and drug-metabolizing enzymes are unknown. This study was to observe the effects of Xuefu Zhuyu decoction (XFZYD) on the activities of antioxidant and drug metabolism enzymes (DMEs) in liver of rats. Male SD rats, treated with XFZYD at the dosage of 3.51, 7.02 and 14.04 g x kg(-1) per day for 15 days, serum were collected, tissue fluid, cytosols and microsomes isolated from liver tissues were prepared by centrifugation according to the standard procedure, the activities of antioxidant enzymes and drug-Metabolizing Enzymes were determined by UV-V is spectrophotometer. In serum, the activities of AST was not significantly affected by the treatment with XFZYD, at the high- est dose, the levels of ALT, Cr and BUN were significantly decreased (P < 0.05). GPX were significantly increased at the dose of 7.02, 14.04 g x kg(-1) (P < 0.05), CAT were significantly increased at the highest dose (P < 0.05). T-SOD was not significantly af- fected by this treatment. In the liver tissue, GPX was significantly increased at the dose of 3.51, 7.02 g x kg(-1) (P < 0.05), GST, CAT and T-SOD were not significantly affected following this treatment. In cytosols, GST was significantly increased at the dose of 3.51 g x kg(-1) (P < 0.05), T-SOD was remarkable induced at the dose of 3.51 and 7.02 g x kg(-1) (P < 0.05). In microsomes, XFZYD had no significant effect on Cytochromeb5, NADPH-Cytochrome P450 reductase, CYP3A, CYP2E1 and UGT, XFZYD significantly in- duced GST at the dose of 3.51 and 7.02 g x kg(-1) (P < 0.05), and the level of GSH were significantly increased by XFZYD at the dose of 3.51, 7.02 and 14.04 g kg(-1) (P < 0.05). These findings suggest XFZYD can induce the activities of GPX, CAT, SOD, GST and increase GSH level in liver of rats, which indicate XFZYD may have detoxification and antioxidant functions.
Subject(s)
Animals , Male , Rats , Antioxidants , Metabolism , Drugs, Chinese Herbal , Pharmacology , Inactivation, Metabolic , Liver , Rats, Sprague-DawleyABSTRACT
AIM@#To study the effect of Buyang Huanwu Decoction (BYHWD) on the antioxidant enzymes and drug-metabolizing enzymes in rat liver.@*METHOD@#Following treatment of rats with BYHWD at 6.42, 12.83, or 25.66 g·kg(-1) per day for 15 days, microsomes and cytosols isolated from the liver tissues were prepared by differential centrifugation according to standard procedures. The activities of the antioxidant enzymes and cytochrome b5, NADPH-cytochrome P450 reductase, CYP3A, CYP2E1, UGT, and GST of the rat livers were determined by UV-Vis spectrophotometer.@*RESULTS@#The activities of ALT, AST, antioxidant enzymes, and the Hepatosomatic Index in serum were not significantly affected. In cytosols, the activity of CAT was significantly increased at the dosage of 12.83 g·kg(-1), and all the other antioxidant activities and MDA levels were not affected by this treatment. BYHWD had no effect on cytochrome b5, NADPH-cytochrome P450 reductase, CYP3A, and UGT. At the highest dose (25.66 g·kg(-1)), the activity of CYP2E1 was significantly inhibited, and the activities of GST and the level of GSH were increased.@*CONCLUSION@#BYHWD is safe for the liver, and has the functions of detoxification and antioxidant. Patients should be cautioned about the herb-drug interaction of BYHWD and CYP2E1 substrates.
Subject(s)
Animals , Male , Antioxidants , Metabolism , Pharmacology , Catalase , Metabolism , Cytochrome P-450 CYP2E1 , Metabolism , Cytosol , Drugs, Chinese Herbal , Pharmacology , Glutathione , Metabolism , Glutathione Transferase , Metabolism , Herb-Drug Interactions , Inactivation, Metabolic , Liver , Microsomes , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To study the inhibitory effect of total saponins of the root and rhizome of Panax notoginseng (PNS) on drug metabolism enzyme CYP3A in rat livers and its kinetic analysis.</p><p><b>METHOD</b>Microsome enzyme was prepared by differential velocity centrifugation. Michaelis constant (Km) and maximum velocity (Vmax) of CYP3A, 50% inhibitory concentration of PNS on CYP3A, and the inhibition type and the inhibition constant of CYP3A (Ki, Kis) of PNS on CYP3A were calculated by Lineweaver-Burk and the low of semi-effect-probit.</p><p><b>RESULT</b>Total saponins of the root and rhizome of panax notoginseng inhibited CYP3A activity, with IC50 of 689.54 mg x L(-1). Compared with the substrate aminopyrine, CYP3A showed Km of 0.036 mmol x L(-1) and Vmax of 21.01 micromol min(-1) x g(-1). Total saponins of the root and rhizome of panax notoginseng showed a mixed inhibition on CYP3A, with the inhibition constants of 247.79 mg x L(-1) (Ki) and 321.79 mg x L(-1) (Kis).</p><p><b>CONCLUSION</b>Total saponins of the root and rhizome of panax notoginseng have a significant effect on CYP3A activity in rat livers.</p>
Subject(s)
Animals , Male , Rats , Cytochrome P-450 CYP3A , Chemistry , Genetics , Metabolism , Cytochrome P-450 CYP3A Inhibitors , Enzyme Inhibitors , Chemistry , Pharmacology , Kinetics , Liver , Chemistry , Panax notoginseng , Chemistry , Rats, Sprague-Dawley , Rhizome , Chemistry , Saponins , Chemistry , PharmacologyABSTRACT
<p><b>BACKGROUND</b>A Chinese family with autosomal dominant central areolar choroidal dystrophy (CACD) was identified. The purpose of this study was to collect the clinical findings from the family and to identify the genetic entity by linkage analysis.</p><p><b>METHODS</b>Forty-three individuals from 3 generations of the family underwent ophthalmologic examinations, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. Affected family members further underwent color vision test, color fundus photography, fluorescein angiography, automated perimetry, and electroretinography. The family was followed up for 30 months. Peripheral venous blood or buccal swabs were collected from each family member and genomic DNA was extracted. Linkage analysis was performed for candidate genes or loci using microsatellite markers.</p><p><b>RESULTS</b>Seven family members in 3 continuous generations were diagnosed as having autosomal dominant CACD. The family showed progressive development of the disease, affecting both male and female. Age of onset of visual disturbances varied between 11 and 50 years. Phenotypic variability among affected individuals was apparent and ranged from relatively normal-appearing fundus with mild parafoveal pigment mottling to geographic atrophy of the macula. Fluorescein angiography showed hyperfluorescent parafoveal changes in early stage or well-demarcated area of chorioretinal atrophy with enhanced visibility of the residual underlying choroidal vessels in the late stage. Peripheral retina and visual fields were normal in affected individuals. Electroretinogram showed normal or mild reduction in the photopic amplitude. Eight candidate genes (STGD4, RCD1, peripherin/RDS, GUCA1A, RIMS1, UNC119, GUCY2D, and AIPL1) and two genetic loci (4p15.2 - 16.3, and 17p13) were excluded to be responsible for the disease by linkage analysis.</p><p><b>CONCLUSIONS</b>The clinical findings of this Chinese family with CACD shared similarities with previously reported families of other ethnicities. Linkage analysis excluded the known genes and genetic loci, indicating genetic heterogeneity of the disease.</p>
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Choroid Diseases , Genetics , Electroretinography , Fluorescein Angiography , Genetic LinkageABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of ginkgolides on gene expression of hepatic cytochrome P-450 in rats.</p><p><b>METHOD</b>Sprague-Dawley rats were administered ginkgolides (100 mg x kg(-1) body weight) through oral gavage once daily for four consecutive days. The level of gene expression in liver tissues was analyzed by competitive reverse transcription-polymerase chain reaction (competitive RT-PCR).</p><p><b>RESULT</b>A single and prospective band of CYP1A1, CYP1A2, CYP2B1/B2, CYP2C11, CYP2E1, CYP4A1 and cyclophilin was observed after polymerase chain reaction (PCR) when the reactive system of reverse transcription (RT) had no target RNA, which confirmed the competitor had a specific capacity to bind to the CYP or cyclophilin primer. CYP1A1 mRNA was not dectectable in the livers of untreated control rats and ginkgolides-treated rats. The levels of CYP2C11 and CYP2E1 were not changed by ginkgolides treatment. In contrast, the levels of gene expression for CYP1A2 and CYP2B1/B2 were decreased, however, the levels of gene expression for CYP3A1 and CYP4A1 in ginkgolides group were distinctly increased compared with the control.</p><p><b>CONCLUSION</b>A specific effect of ginkgolides on cytochrome P-450 gene expression was observed in this investigation. Ginkgolides had various effects on different cytochrome P-450 isoforms.</p>
Subject(s)
Animals , Male , Rats , Aryl Hydrocarbon Hydroxylases , Genetics , Cytochrome P-450 CYP1A1 , Genetics , Cytochrome P-450 CYP1A2 , Genetics , Cytochrome P-450 CYP2B1 , Genetics , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System , Genetics , Cytochrome P450 Family 4 , Gene Expression Regulation , Ginkgo biloba , Chemistry , Ginkgolides , Pharmacology , Liver , Metabolism , Plants, Medicinal , Chemistry , RNA, Messenger , Genetics , Random Allocation , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To review the effects of the active components of Chinese herbs on drug metabolizing-enzymes.</p><p><b>METHOD</b>Relevant research papers reported in recent years were consulted and studied.</p><p><b>RESULT</b>The drug metabolizing-enzymes cytochrome P450 and UDP-glucuronosyl transferase and glutathione S-transferase were inhibited or induced by the flavonoids, furocoumarins, and the active components extracted from salvia miltiorrhiza and hypericum perforatum, and so on, which therefore slowed or sped metabolism of other drugs in vivo and in vitro.</p><p><b>CONCLUSION</b>Much attention should be paid to the metabolic interaction of the Chinese herbs when coadministered with other drugs.</p>
Subject(s)
Animals , Humans , Cytochrome P-450 Enzyme System , Metabolism , Flavonoids , Pharmacology , Furocoumarins , Pharmacology , Glucuronosyltransferase , Metabolism , Glutathione Transferase , Metabolism , Plants, Medicinal , Chemistry , Salvia miltiorrhiza , ChemistryABSTRACT
The symbiotic bacterium exists in the intestines of entomopathogenic nematodes and is a potential biological agent.Systematic classification of these bacteria is scarce in China.In this paper,seven strains of symbiotic bacteria from local entomopathogenic nematodes were identified by both observation of mor-phology,physiological,biochemical characteristics and sequence analysis of 16S rDNA fragments.