ABSTRACT
Protein polypeptides and polysaccharides, the indispensable macromolecular active components in traditional Chinese medicine, are widely found in Chinese medicine decoction after the decoction of traditional Chinese medicine. However, through oral administration, these macromolecules are digested by the stomach and intestine and thus fail to be absorbed in prototype. This is inconsistent with the actual clinical efficacy of Chinese medicine decoction. According to modern research, new phase structures and effects of the macromolecules emerge during the decoction of traditional Chinese medicine, but the phase change law caused by the interaction among the components of traditional Chinese medicine and the relationship between phase structure and effect are still unclear. Thus, this study reviewed the oral absorption of macromolecular components of traditional Chinese medicine, analyzed the internal relationship of the form of macromolecules in traditional Chinese medicine with the absorption and effect based on phase structure, and summarized the research mode of oral absorption and effect of macromolecules in traditional Chinese medicine with phase structures as the core, providing new ideas and methods for future research.
Subject(s)
Medicine, Chinese Traditional , Drugs, Chinese Herbal/chemistry , Stomach , Administration, OralABSTRACT
Chinese medicine self-assembly nano-strategies（CSAN） is to utilize the self-assembly property of Chinese medicine components， so that the Chinese medicine components can self-assemble to form structurally stable nano-preparations through non-covalent interactions. The formation of Chinese medicine self-assembly nano-preparations is often a synergistic result of a variety of non-covalent interactions， and many Chinese medicine monomers are susceptible to self-assembly due to their structural characteristics， and the phenomenon of self-assembly of Chinese medicine is also common in the decoction of single or compound Chinese medicine， which has attracted the attention of researchers. It is found that CSAN can improve the solubility and bioavailability of active components in Chinese medicine， which is of positive significance for the development and application of insoluble components of Chinese medicine. The self-assembly phenomenon of Chinese medicine decoction is closely related to the therapeutic efficacy， and the study of self-assembly phenomenon of Chinese medicine will bring a new perspective for the explanation of the mechanism of Chinese medicine decoction. At the same time， traditional Chinese medicine（TCM） has unique advantages in the field of anti-tumor. The application of CSAN in the field of oncology can not only exert the anti-tumor effect of the active components of Chinese medicine directly， but also act as a natural nano-carrier to carry chemotherapy drugs for combination chemotherapy， improve the targeting of drugs， enhance the anti-tumor efficacy， and reduce the side effects of chemotherapy， which has excellent anti-tumor potential. The preparation method of Chinese medicine self-assembly nano-preparations is simple， low cost， and has better safety than traditional nano-preparations， which is conducive to the promotion of the clinical transformation of nano-preparations， and also helps to provide new strategies and perspectives for promoting the modernization of TCM. Therefore， based on a large number of researches in this field in recent years， this paper reviewed the formation mechanism， different assembly forms， formation conditions and stability of Chinese medicine self-assembly nano-preparations by searching databases such as China national knowledge infrastructure（CNKI）， PubMed， WanFang data and VIP， and summarized the application of CSAN in different tumor therapies， providing a reference for further research on CSAN.
ABSTRACT
Objective:To evaluate the effect of chicoric acid on oxidative stress during myocardial injury in sepsis rats and the relationship with nuclear factor E2-related factor 2 (Nrf2) signaling pathway.Methods:Forty healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 220-250 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), lipopolysaccharide (LPS) group (group LPS), LPS+ chicoric acid group (group LPS+ CA), LPS+ Nrf2 inhibitor ML385 group (group LPS+ ML) and LPS+ chicoric acid+ ML385 group (group LPS+ CA+ ML). LPS 15 mg/kg was intraperitoneally injected to induce sepsis.Immediately after intraperitoneal injection of LPS, chicoric acid 10 mg/kg or ML385 15 mg/kg (in dimethyl sulfoxide) was intraperitoneally injected in group LPS+ CA and group LPS+ ML, respectively, and ML385 15 mg/kg and chicoric acid 10 mg/kg were intraperitoneally injected in LPS+ CA+ ML group.The equal volume of dimethyl sulfoxide was given instead in group C. At 48 h after establishment of the model, blood samples were collected from the aorta for measurement of concentration of serum interleukin-6 (IL-6) and the activities of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) (by enzyme-linked immunosorbent assay). The animals were then sacrificed, and myocardial tissues were obtained for microscopic examination of pathological changes (by HE staining), for determination of activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and contents of reactive oxygen species(ROS) and iron (by colorimetry), for calculation of the ratio of oxidized nicotinamide adenine 2 nucleotides to reduced nicotinamide adenine 2 nucleotides (NAD + /NADH), and for detection of the expression of Nrf2, NADPH quinone oxidoreductase 1 (NQO1), glutathione peroxidase 4 (GPX4) and nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) (by Western blot). Results:Compared with C group, the activities of serum LDH and CK-MB and concentration of IL-6 were significantly increased, the contents of ROS and iron and the ratio of NAD + /NADH were increased, activities of GSH-Px and SOD were decreased, expression of Nrf2, NQO1 and GPX4 was down-regulated, and NOX1 expression was up-regulated in the other four groups ( P<0.05). Compared with group LPS, the activities of serum LDH and CK-MB and concentration of IL-6 were significantly decreased, the contents of ROS and iron and the ratio of NAD + /NADH were decreased, activities of GSH-Px and SOD were increased, expression of Nrf2, NQO1 and GPX4 was up-regulated, NOX1 expression was down-regulated ( P<0.05), and the pathological changes of cardiomyocytes were significantly reduced in group LPS+ CA, and the activities of serum LDH and CK-MB and concentration of IL-6 were significantly increased, the ratio of NAD + /NADH were increased, activities of GSH-Px and SOD were decreased, expression of Nrf2, NQO1 and GPX4 was down-regulated, NOX1 expression was up-regulated ( P<0.05), and the pathological changes of cardiomyocytes were accentuated in group LPS+ ML.Compared with group LPS+ CA, the activities of serum LDH and CK-MB and concentration of IL-6 were significantly increased, the contents of ROS and iron and the ratio of NAD + /NADH were increased, activities of GSH-Px and SOD were decreased, expression of Nrf2, NQO1 and GPX4 was down-regulated, NOX1 expression was up-regulated ( P<0.05), and the pathological changes of cardiomyocytes were accentuated in group LPS+ CA+ ML. Conclusion:The mechanism by which chicoric acid reduces myocardial injury in sepsis rats may be related to activating Nrf2 signaling pathway and inhibiting oxidative stress.
ABSTRACT
The origin and distribution of oligosaccharides of TCM are extensive, and its special biological activity and chemical properties have great potential in health preserving and disease prevention and treatment. The researches about its components are increasing, and its research and application are expanded. Oligosaccharides of TCM can be obtained by natural extraction, degradation and artificial synthesis. Among them, the natural extraction method is the most suitable for chromatography. The oligosaccharides of TCM have different groups and connections, and the structure is complex, with different chemical reactions in the process. This article reviewed the research overview of oligosaccharides of TCM from the aspects of separation, biological activity and chemical reactions in the process.
ABSTRACT
Objective To study the clinical effect of biofeedback stimulation combined with hypogastric plexus blocking on chronic pelvic pain.Methods Sixty of patients with chronic pelvic pain(CPP)were randomly divided into the biofeedback stimulation group(BF group,n = 20),the continuous abdominal block group(NB group,n = 20)and the combination group(BF-NB Group,n = 20). The BF group was treated with biofeedback electrical stimulation for 2 months,while the NB group was treated with continuous hypogastric plexus blocking for 2 weeks and the BF-NB group was pre-treated with 2 weeks of hypogastric plexus blocking and then underwent biofeedback electrical stimulation for 2 months. We recorded the visual analogue scale(VAS)scores before treatment,2,4,8 weeks and 3 months after the treatment and adverse events.Results The VAS scores of the BF-NB group at 2,4,8 weeks and 3 months after treatment were significantly lower than those before treatment and the other groups(P<0.05).The significantly effective rate and total effective rate of the BF-NB group were signifi-cantly higher than those before treatment of the BF group and the NB group(P < 0.05). There was no significant difference in rate of adverse events between the BF-NB group and the NB group(P>0.05).Conclusion The bio-feedback electrical stimulation combined with the hypogastric plexus block is a safe and effective method to relieve chronic pelvic pain.
ABSTRACT
Objective To compare the license issuance and status of administration of laboratory animals in Jiangsu and Zhejiang provinces in the last five years, and to study the status of laboratory animal license management and industry development level in the two provinces.Methods Taking a combination of current status investigation, literature search, information collection and comparative analysis, to study the similarities and differences in the annual issuance of laboratory animal licenses, level of environmental facility, type of institution division, regional distribution of institutions, etc.in the two provinces over the last five years.Results Over the past five years, the total number of the issued laboratory animal licenses and approved institutions in Jiangsu province are significantly more than in Zhejiang province.The proportion of barrier environmental facilities in Jiangsu is slightly higher than that in Zhejiang.Laboratory animal institutions cover most areas of the provinces, relatively concentrated in the capital cities and economically developed cities.The business type institutions account for the highest percentage in the two provinces.Animal species in the two provinces are approximately the same.Conclusions The industrial structure of the laboratory animals in Jiangsu province is more perfect than that in Zhejiang province.Industrialization and socialization get a higher degree in Jiangsu province.The range of regular species of the laboratory animals needs to be further expanded.The competent departments need further optimize and promote license management system of the laboratory animals.
ABSTRACT
<p><b>OBJECTIVE</b>Many metals, some of which have been classified as environmental endocrine disruptors, are used extensively in everyday consumer products and are ubiquitous in our living environment. In the present study, we aimed to explore the associations between the prevalence risk of type 2 diabetes and plasma levels of 20 trace elements as well as those of heavy metals in a Han Chinese population.</p><p><b>METHODS</b>We conducted a case-control study to investigate the associations between plasma concentrations of 20 metals and diabetes in Jiangsu province. A total of 122 newly diagnosed cases of type 2 diabetes and 429 matched controls were recruited from community physical examinations in Suzhou City of Jiangsu Province. Plasma metal levels were measured by inductively-coupled plasma mass spectrometry.</p><p><b>RESULTS</b>After adjusting for confounders, plasma vanadium, chromium, manganese, copper, zinc, arsenic, selenium, strontium, palladium, cadmium, cesium, and barium were associated with diabetes risk (P < 0.05). The adjusted OR increased with increasing concentration of vanadium, manganese, copper, zinc, and cesium.</p><p><b>CONCLUSION</b>Many metals, including manganese, copper, zinc, arsenic, selenium, and cadmium in plasma, are associated with the morbidity of diabetes. Monitoring of environmental metal levels and further studies are urgently needed.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Case-Control Studies , Diabetes Mellitus , Blood , Environmental Pollutants , Blood , Toxicity , Metals , Blood , Risk FactorsABSTRACT
Objective To investigate the effects of rapid colloid and crystalloid infusions on the plasma concentration of propofol( Cp) during target-controlled infusion.Methods Thirty-six patients were randomly assigned to three interventions(12 patients per group).At least 30 min after the start of propofol infusion,the hydroxyethyl starch solution group(HES)received HES of 24 mL/(kg· h),on the former 20 min,the sodium acetate Ringer’s injection group(AR)received AR of 24 mL/(kg· h),while HES group and AR group of later 20 min and the control group of whole course received AR of 2 mL/(kg· h).The plasma concentrations of propofol were recorded per 2 min and a half.The cardiac outputting,blood volume and clearance of indocyanine green were measured by pulsed dye density analyzer,the effective hepatic blood flow( EHBF) were obtained.Results The varying of Cp with time showed a significant treatment factor(F[2,33] =14.14,P<0.001)and time factor(F[16,528] =10.37,P<0.001)and interaction between the above factors(F[32,528] =2.82,P <0.001) by ANOVA for repeated measurement;the difference of Cp among each group,Cp in HES group was significantly lower than AR group(5-40 min)or control group(10-40 min),with significant difference(P<0.05).The varying of EHBF with time showed a significant treatment factor(F[2,28] =3.68,P=0.038)and time factor(F[2,56] =5.37,P=0.007)and interaction between the above factors(F [4,56] =3.67,P=0.010);while there was no significant difference in other groups.Conclusion Rapid HES infusion increases the effective hepatic blood flow,resulting in a decrease of propofol concentration during target-controlled infusion.Rapid HES infusion should be used cautiously as it may decrease the depth of anesthesia.
ABSTRACT
Objective To explore the neural damage induced by acute exposure to methamphetamine (METH).Methods The mice were administrated with METH,then the stereotyped behavior of mice was evaluated,and spatial recognition memory was analyzed by Y-maze test.In addition,nitric oxide synthase (NOS) activity was detected by kit,and the apoptotic proteins including Bax,Bcl-2,Caspase-3 were assayed by using Western blot.The DNA injury induced by METH was observed by using the comet assay.Moreover,mitochondrial membrane potential was detected to assess the toxic effects of METH on mitochondria by JC-1.With the Western blot assay,the phosphorylation of MAPK signaling pathways were also investigated.Results Acute METH exposure significantly increased the stereotyped behavior in mice,and spatial recognition ability of mice was obviously decreased.On the molecular level,total nitric oxide synthase (TNOS) and induced nitric oxide synthase (iNOS) were increased,and the apoptotic proteins,such as Bax and cleaved caspase-3 were markedly enhanced.With the comet assay,it showed that METH exposure resulted in DNA damage.In parallel,mitochondrial membrane was damaged which manifested as mitochondrial membrane potential decreased.With the western blot,It was further found that METH enhanced the activation of MAPKs.However,p38 MAPK signahng pathway was demonstrated to be the only one factor involved in METH-induced neural damage.Conclusion METH induced neural damage,and MAPK signaling pathways might be involved in this process,since inhibition of p38 MAPK signaling pathway significantly ameliorated METH-induced neural damage.
ABSTRACT
Objective To investigate the effects of methycobal on the expression of Caspase-3 in brain tissue after cerebral ischemia reperfusion in rats. Methods Rats were randomly divided into sham-operation group, model control group, nimodipine group and low-dose methycobal group, high-dose methycobal group(n=30 in each group).Rats in the sham-operation group and model control group were administered intragastrically with 0.9% sodium chloride solution, rats in the nimodipine group were treated with 1 mg . kg-1 . d-1 of nimodipine, rats in the low- and high-dose of methycobal groups were given 50 and 100 μg.kg-1 .d-1 of methycobal, respectively. The rat model of cerebral ischemia reperfusion was established by middle cerebral artery occlusion with suture method for 3 h.Neurological deficit scores were evaluated 24 h after reperfusion.The apoptosis of perifocal cortex cells was detected by TUNEL method and the expression of Caspase-3 was analyzed by RT-PCR 6, 12 and 24 h after reperfusion. Results Neurological deficit scores in model control group, nimodipine group, low-dose methycobal group and high-dose methycobal group were 2.70±0.52, 1.30±0.51, 2.20±0.75 and 1.30±0.81, respectively.Compared with model control group, neurological deficit scores were significantly different in the nimodipine group, low-dose methycobal group and high-dose methycobal group(P0. 05 ) . There was a significant difference between the high-dose methycobal group and low-dose methycobal group( P0.05).There were significant differences between the high-dose methycobal group and low-dose methycobal group at the end of 24 h(P<0.05). Conclusion Methycobal can protect the brain cells from injury after cerebral ischemia reperfusion by adjusting the expression of Caspase-3m RNA, and the high-dose methycobal is more effective.
ABSTRACT
Objective To explore the correlation of bone metabolism levels and risk of coronary heart disease in elder women patients .Methods A total of 163 elder women patients were divided into three group:CON group ,CAD group ,and CHD group .We explored related atherosclerosis risk factors and factors related to bone metabolism .Results Compared with CON group ,there was no statistical significance in CAD group in factors related to bone metabolism(P>0 .05) .In CHD group ,serum 25‐OH‐Vitamin D significantly decreased and β‐C‐terminal telopeptide of type Ⅰ collagen significantly increased compared with CON group(P<0 .05) .Compared with CAD group ,the serum 25‐OH‐Vitamin C also significantly decreased andβ‐C‐terminal telopeptide of type Ⅰcollagen significantly increased(P< 0 .05) .Spearman correlation analysis showed that BMI ,HDL‐C ,triglycerides ,LDL‐C ,blood glucose and 25‐OH‐Vitamin D were correlated with coronary heart disease .With coronary heart disease as the dependent variable , the results showed lower LDL‐C ,25‐OH‐Vitamin D had independent predictive value for the risk coronary heart disease .Conclusion Lower 25‐OH‐Vitamin D levels in elder patients were positively correlated with coronary heart disease ,and it might also be an in‐dependent predictor .
ABSTRACT
Objective: Huangqi Injection is a preparation with an extract of Astragali Radix which has a long history of being used as a tonic to strengthen the body's immunity. Anaphylaxis and hemolysis are two main adverse drug reaction (ADR) of injections. Our study was aimed to establish an approach for the (ADR) prediagnosis of Huangqi Injection. Methods: An in vitro model for anaphylactoid assay of Huangqi Injection based on the release rate of histamine and β-hexosaminidase of RBL-2H3 cells induced by injections and a colorimetric method based on the detection of hemoglobin resulted in the erythrocyte hemolysis for prediagnostic assaying the hemolytic ADR of injections were established. Results: Both histamine and β-hexosaminidase are the anaphylactiod mediators, but β-hexosaminidase release induced by Huangqi Injection could not be determined by spectrophotometry due to the interference of the injection itself. In addition, normal hemolysis and abnormal hemolysis were discovered during the experiment. The fingerprints and tannins in different batches of injections showed obvious differences, indicating that the content of tannins was related to abnormal hemolysis and higher histamine-secreting from RBL-2H3 cells. Conclusion: The results indicate that the hemolytic assaying method is not only suitable for prediagnostic assaying of hemolytic ADR of herbal medicine injection, but also partly reflects the anaphylaxis of herbal injections, and tannins may be the major factors causing abnormal hemolysis.
ABSTRACT
Aim To investigate the analgesic effect of tetrahydropalmatine on Cav1 . 2 expression in the dorsal root ganglion ( DRG) of mice with sciatic nerve chronic constriction injury ( CCI ) -induced neuropathic pain. Methods Forty male C57 BL/6 mice were randomly divided into 5 groups ( n =5 ): sham group ( group S) , CCI group ( group C ) and L-THP group ( group L) . Steady mice models of neuropathic pain were es-tablished by inducing CCI of sciatic nerve. According to development of neuropathic pain in mice, L group was divided into induction period, induction with ma-intenance period and long-term low-dose group. The mice were intraperitoneally administered with 45 mg · kg-1 tetrahydropalmatine in induction ( day 0~5 ) , in-duction with maintenance ( day 0~5 , 14~19 ) period of neuropathic pain state. From the instant after opera-tion, 15 mg · kg-1 tetrahydropalmatine was injected into the long-term low-dose group once per day for 19 days. Then, the behavior changes of mice were moni-tored. Moreover, the threshold of mechanical and ther-mal stimuli was tested. In addition, the expression of Cav1 . 2 protein was detected by Western blot and im-munohistochemical staining. Results The lowest ex-pression of Cav1 . 2 was observed in group C and the highest expression level of Cav1 . 2 was found in group S. Cav1. 2 expression was significantly up-regulated in induction period group, induction with maintenance period group and long-term low-dose group ( P0. 05 ) in long-term low-dose group. Conclusions High dose of tet-rahydropalmatine in induction period group, induction with maintenance period group and low-dose among the whole experiment process obviously relieves the neuro-pathic pain induced by nerve injury. The analgesic effect of tetrahydropalmatine on neuropathic pain may be due to the increased expression of Cav1 . 2 protein in DRG neurons.
ABSTRACT
Objective To observe the effect of restrictive transfusion in colon cancer surgery in elderly patients on postoperative VAP (ventilator-associated pneumonia). Methods Forty cases of elderly patients with colon cancer intending to undertake surgery were randomly divided into restrictive transfusion group (group R) and standard transfusion group (group S) with 20 cases in each group. In group R, patients were administered one third of accumulative fluid loss in the first 60 minute, then the infusion rate were 4 mL/(kg·h) and central venous pressure was maintained at 5 ~ 7 cmH2O. In group S, rate of fluid administration = CVE + deficit +maintenance + loss + third space. Blood gas index including lactic acid and volumes of fluid administered, blood loss, urine volume and thoracic fluid count (TFC) were recorded in the operation. Clinical pulmonary infection score(CPIS) was recorded respectively before operation, 1 day, 3 day, 7 day after operation to evaluate the risk of VAP. Results Compare with those in group S, there were significantly less TFC and intraoperative volumes of fluid administration in group R. The CPIS was significant lower at day1, day3, day7 after operation in group R. There was no significant difference in MAP, HR, CO and urine volume between two groups. Conclusions In colon cancer surgery for elderly patients, restrictive transfusion can maintain hemodynamic stability, ensure the tissue oxygenation, reduce conjunction edema, shorten the recovery and hospital stay and reduce the incidence of VAP.
ABSTRACT
Objective To explore the relationship of the severity of coronary-artery stenosis with plasma levels of brain natriuretic peptide (BNP) and Meprin-α.Methods Totally 237 patients in our hospital were divided into control group (CON group), stable angina group (SA group) and acute coronary syndrome group (ACS group), according to coronary artery angiography.Patients with acute coronary syndrome were divided into 3 subgroups: unstable angina (UA) group, non-ST segment elevation myocardial infarction (NSTEMI) group and ST segment elevation myocardial infarction (STEMI) group.Patients with coronary artery disease (CAD) were divided into 3 subgroups: low-score, medium-score and high-score groups, according to coronary angiography and Syntax score.BNP and Meprin-α levels were determined in patients with coronary artery disease, and the degree of coronary artery stenosis was evaluated.The differences in above indexes were analyzed and compared among the three groups.Results Plasma levels of BNP and Meprin-α were higher in ACS group than in CON group [(233.16± 78.22)ng/L vs.(33.48 ± 13.71)ng/L, (26.89 ± 6.45) nmol/L vs.(12.83±0.66)nmol/L, both P＜0.05].Compared with UA group, plasma levels of BNP and Meprin-α were increased in NSTEMI and STEMI groups (all P＜0.05).Compared with the control group, plasma levels of BNP and Meprin-α in the Syntax scores-divided subgroups were increased (all P＜ 0.05).The plasma levels of BNP and Meprin-α in CAD patients were significantly increased along with the increase of Syntax Score.Spearman correlation analysis showed that low density lipoprotein cholesterol, glucose, BNP and Meprin-α levels had positive correlations with the occurrence of coronary heart disease, while high density lipoprotein level was negatively correlated with the occurrence of coronary heart disease (all P＜0.05).Conclusions BNP and Meprin-α levels in peripheral blood are significantly elevated in patients with coronary heart disease, and they are correlated with Syntax score.The risk of ACS is increased along with the increased BNP and Meprinα levels.
ABSTRACT
BACKGROUND: Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic stroke. This study aimed to explore the association of ALOX5,LTA4H andLTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China.METHODS: This case-control study consisted of 690 patients with ischemic stroke and 690 controls. Polymorphisms ofALOX5 rs2029253 A/G,LTA4H rs6538697 T/C, andLTC4S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. The multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic stroke.RESULTS: Carriers of C allele in rs730012 were more susceptible to ischemic stroke (OR: 1.37; 95%CI: 1.08-1.73;P=0.009). The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke (OR: 0.72; 95%CI: 0.55-0.93;P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke (OR: 1.77; 95%CI: 1.09-2.89;P=0.022). The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors (P>0.05).CONCLUSION: The present study suggested that gene polymorphisms in the leukotrienes pathway may exert infl uences, with independent genetic effects, on ischemic stroke susceptibility in a cohort of Chinese in east China.
ABSTRACT
<p><b>BACKGROUND</b>Leukotrienes are arachidonic acid derivatives long known for their inflammatory properties. Leukotriene-based inflammation has been demonstrated to play a crucial role in atherosclerosis, a major risk factor for several human diseases. Recently, human genetic studies from us and others suggest that single nucleotide polymorphisms (SNPs) in leukotriene pathway genes influence the risk of atherosclerotic diseases such as stroke. This study aimed to assess the role of additional leukotriene pathway genes as a stroke risk factor within the Chinese Han population.</p><p><b>METHODS</b>We sequenced the promoter, exonic, and intronic regions of leukotriene A4 hydrolase (LTA4H) and arachidonate 5-lipoxygenase (ALOX5), and then genotyped five SNPs in LTA4H and four SNPs in ALOX5 among 691 cases with stroke and 732 controls from the Chinese population.</p><p><b>RESULTS</b>We detected a significant association between an intronic SNP in LTA4H (rs6538697) and stroke in our subjects (adjusted odds ratio, recessive model, 1.75; P = 0.022); and the SNP rs2029253 in ALOX5 was associated with a decreased risk of stroke (adjusted odds ratio, 0.76; 95% confidence interval, 0.59 - 0.97).</p><p><b>CONCLUSION</b>Genetic variants in LTA4H and ALOX5 may modulate the risk of stroke in the Chinese Han population.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Asian People , Genetics , Case-Control Studies , Leukotrienes , Logistic Models , Polymorphism, Single Nucleotide , Risk , Stroke , GeneticsABSTRACT
Objective To investigate the effects of methamphetamine (Meth) on the outward K+ currents and elucidate the role of outward K+ channels in Meth induced hippocampal neuron damage.Methods Hippocampal neurons were harvest from 18-day-old embryonic rats and were divided into two groups:the control group and the Meth treated group.Both of 4-AP and TEA sensitive K+ currents were recorded after the treatment of Meth by performing the whole cell patch clamp.Furthermore,the MTT and TUNEL assays were performed to evaluate the effects of K+ channel on hippocampal neuron damage mediated by Meth.For statistical comparison,One-way ANOVA and LSD multiple comparison test or t-test was used.P-value ＜ 0.05 was considered to be statistically significant.Results The density of 4-AP sensitive K+ channel currents in Meth treated group [(120.1 ± 19.6) pA/pF,n =7] were significantly increased when compared with control group [(87.4 ± 12.5) pA/pF,n =10,P ＜0.01] and the increments of the currents induced by Meth was dose dependent.The MTT data showed that the cell viability was obviously decreased in Meth treated group (48.72 ± 4.38) ％ relative to the control group (100.07 ± 3.36) ％.Moreover,application of K+ channel antagonist,4-AP (61.39 ± 3.15)％,and the high K+ solution (78.25 ± 9.42) ％ substantially enhanced the cell viability.The TUNEL assay showed there were protective effects of 4-AP and the high K+ solution against neuron damage observed during cells exposed to Meth.Conclusions The increments of 4-AP sensitive K+ channel currents induced by Meth might be involved in hippocampal neuron damage.
ABSTRACT
BACKGROUND: 5-lipoxygenase protein (ALOX5AP) has been recognized as a susceptibility gene for stroke and coronary artery diseases. The present study was to explore the role of this gene in the eastern Chinese patients with ischemic stroke.METHODS: Using a case-control design, we studied 658 patients with ischemic stroke and 704 unrelated population-based controls who were age- and sex-matched. The 658 patients were classified by the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Two single-nucleotide polymorphisms (SNPs) covering ALOX5AP were genotyped.RESULTS: The genotype frequencies of TG of the SNPs rs17222919 located in the promoter of the ALOX5AP gene were significantly higher in patients with ischemic stroke than in controls (OR*=1.34, 95％CI*=1.02-1.75), especially in patients with ischemic stroke caused by small-artery occlusion (SAO) (OR*=1.40, 95％CI*=1.02-1.93). Meanwhile, the genotype frequencies of TG and TG/GG were higher in female patients than in the controls. After specification, the genotype frequencies of TG and TG/GG were higher in the patients than in controls with hypertension. The genotype frequencies of AG and AG/GG of the SNPs rs9579646 located in the intron of the ALOX5AP gene were higher in the controls than in the patients. After specification, the genotype frequencies of TG were higher in the controls than patients without hypertension.CONCLUSION: The present study suggests that sequence variants in the ALOX5AP gene are significantly associated with ischemic stroke.
ABSTRACT
Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis(TM), we identified genes (up- or down-regulated, > or = 1.5 fold, P < or = 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 microg/ml) in UtLM cells. Downregulation of TGF-beta signaling pathway genes, activin A, activin B, Smad3, TGF-beta2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that down-regulation of activin A and Smad3, both members of the TGF-beta pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.