Polymorphism of Human Organic Cationic Transporter1 (C480G) in Egyptian Chronic Myeloid Leukemia Patients on Imatinib

Background: Human organic cationic transporter1 (Hoct1) is a plasma membrane transporter responsible for the main influx of Imatinib into chronic myeloid leukemia (CML) cells. Single nucleotide polymorphisms (SNPs) in the gene coding for hOCT1 are important factors causing Imatinib resistance. We investigated the frequency of hOCT1 SNP C480G among Egyptian CML patients and its relation to early molecular response as an indicator of treatment outcome. Materials and Methods: Two groups of CML patients were included in this study. Group I consisted of 25 patients responding to Imatinib treatment (Imatinib responsive) and group II consisted of 25 patients resistant to Imatinib (Imatinib resistant). Response criteria were assessed according to the NCCN (National Comprehensive Cancer Network) guidelines 2017. Twenty healthy controls of matched age and sex were also included (group III). For all patients, we studied hOCT1 C480G at initial presentation using Taqman drug metabolism genotyping as well as BCR-ABL percent at diagnosis and after 3 months interval. Results: hOCT1 C480G was present in 32% of studied CML patients. CC (wild) was detected in 68% of group I and 64% of group II. CG (mutant heterozygous) was present in 28% of group I and 36% of group II while GG (mutant homozygous) was detected in only one case in group I. CG was also detected in 15% of control subjects There was no significant difference between hOCT1 C480G polymorphism and Early Molecular Response (χ2 = 0.089, p = 0.765). Conclusions: hOCT1 C480G polymorphism has no association with Imatinib resistance in Egyptian population. However, further studies on a larger number of patients are still needed to confirm this finding.

Effect of exercise during pregnancy on offspring development through ameliorating high glucose and hypoxia in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)women require prenatal care to minimize short-and long-term complications.The mechanism by which exercise during pregnancy affects organ development and whether glucose transporter(GLUT)1 plays a role in GDM offspring organ development remains unknown.AIM To determine the effect of exercise during pregnancy on the cardiac,hepatic and renal development of GDM mother’s offspring.METHODS Placenta samples were collected from humans and mice.GDM mouse models were created using streptozotocin along with a GDM with exercise group.The hearts,livers and kidneys of 3-and 8-week-old offspring were collected for body composition analysis and staining.The effects of high glucose levels and hypoxia were investigated using HTR8/SVneo.Transwell and wound-healing assays were performed to assess cell migration.Immunofluorescence accompanied with TUNEL and Ki67 staining was used to explore apoptosis and proliferation.RESULTS Exercise during pregnancy downregulated the GLUT1 and hypoxia inducible factor-1αexpression in placenta from individuals with GDM.Cobalt chloride induced hypoxia and high glucose levels also significantly decreased migration and apoptosis of HTR8/SVneo cells.In addition,exercise reduced inflammatory cell infiltration in the liver and decreased the tubular vacuolar area in the kidneys of offspring.CONCLUSION GDM affects the growth and development of organs in offspring.Exercise during pregnancy can reverse adverse effects of GDM on the development of the heart,liver,and kidney in offspring.

Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer

BACKGROUND There are limited data on the use of glucose transport protein 1(GLUT-1)expre-ssion as a biomarker for predicting lymph node metastasis in patients with colorectal cancer.GLUT-1 and GLUT-3,hexokinase(HK)-II,and hypoxia-induced factor(HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose(FDG)uptake on positron emission tomography/computed tomography(PET/CT).AIM To evaluate GLUT-1,GLUT-3,HK-II,and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT.METHODS This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012.Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist,and the expressions of GLUT-1,GLUT-3,HK-II,and HIF-1 were determined using immunohisto-chemical staining.We analyzed the correlations among their expressions,various clinicopathological factors,and the maximum standardized uptake value(SUVmax)of PET/CT.RESULTS GLUT-1 was found at the center or periphery of the tumors in 109(64.5%)of the 169 patients.GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes,regardless of the biopsy site(tumor center,P<0.001 and P=0.012;tumor periphery,P=0.030 and P=0.010,respectively).GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT,respectively,for the detection of lymph node metastasis,regardless of the biopsy site.GLUT3,HK-II,and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes.CONCLUSION GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes.Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings.

小麦硝酸盐转运蛋白基因TaNRT1.1的鉴定及其等位变异分析

为解析小麦硝酸盐转运蛋白基因TaNRT1.1的生物学功能,本研究通过同源克隆的方法从普通小麦中克隆了小麦硝酸盐转运蛋白基因TaNRT1.1(TaNRT1.1-1A、TaNRT1.1-1B和TaNRT1.1-1D)。生物信息学分析表明,这三个同源基因编码的蛋白均为疏水蛋白,含有丰富的α-螺旋和无未见则卷曲,主要定位于质膜上。小麦不同组织qRT-PCR分析表明,TaNRT1.1-1A和TaNRT1.1-1B基因在根中表达量最高,其次是叶和茎,TaNRT1.1-1D基因在茎中表达量最高,其次是叶和根。因此,推测TaNRT1.1-1A和TaNRT1.1-1B基因在硝酸盐吸收过程中发挥了重要作用,TaNRT1.1-1D基因在硝酸盐转运过程中发挥了重要作用。通过对小麦TaNRT1.1基因多态性筛选发现,在TaNRT1.1-1A基因启动子上游1120 bp的位置有一个8 bp(TGCATGCA)的插入位点,该位点可能与小麦氮利用效率相关。不同氮利用效率小麦品种qRT-PCR分析结果表明,氮高效小麦品种(基因型为TaNRT1.1-1A-b)苗期根中TaNRT1.1-1A基因的相对表达量显著高于氮低效小麦品种(基因型为TaNRT1.1-1A-a)。

Tumor cell membrane-coated continuous electrochemical sensor for GLUT1 inhibitor screening

Glucose transporter 1(GLUT1)overexpression in tumor cells is a potential target for drug therapy,but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds.With current analysis techniques,it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in real-time.We developed a cell membrane-based glucose sensor(CMGS)that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional Chinese medicines(TCMs).CMGS is compatible with cell membranes of various origins,including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small molecules.Based on CMGS continuous monitoring technique,we investigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 expression.We used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins families.Results were consistent with those of the cellular glucose uptake test and molecular-docking simulation.CMGS could accurately screen drug molecules in TCMs that inhibit GLUT1,providing a new strategy for studying transmembrane protein-receptor interactions.

Two pyrrole acids isolated from Phyllanthus emblica L.and their bioactivities

An undescribed pyrrole acid,1-(4′-methoxy-4′-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid(1)and one known pyr-role acid(2)were isolated from the fruits of Phyllanthus emblica.The structures of these compounds were elucidated via the comprehensive analyses of IR,HRESIMS,1D and 2D spectroscopic data.A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide(NO),interleukin-6(IL-6),monocyte chemotactic protein 1(MCP-1)and tumor necrosis factor-α(TNF-α)by reducing the phosphorylation of extracellular regulated protein kinases(ERK)and c-Jun N-terminal kinases(JNK)in RAW 264.7 cells.Additionally,compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages.

钠-葡萄糖协同转运蛋白2抑制剂沙库巴曲缬沙坦钠片分别联合阿托伐他汀治疗心肌梗死的疗效及对血清癌胚抗原和乳脂球表皮生长因子-E8影响

目的探讨钠-葡萄糖协同转运蛋白2抑制剂(SGLT2)、沙库巴曲缬沙坦钠片分别联合阿托伐他汀治疗心肌梗死的疗效及对血清癌胚抗原(CEA)及乳脂球表皮生长因子-E8(MFG-E8)影响。方法将160例心肌梗死患者根据用药方法不同分为3组,对照组(60例)、观察A组(50例)和观察B组(50例)。对照组介入治疗后采取降压、调脂、抗感染等常规治疗措施,并口服阿司匹林、氯吡格雷。观察A组在对照组基础上应用诺欣妥联合阿托伐他汀治疗,观察B组在对照组基础上应用SGLT2联合阿托伐他汀治疗。对比3组患者治疗总有效率,治疗前后心功能、心肌酶谱变化情况以及不良反应发生率。结果观察A组与观察B组总有效率高于对照组(92%、88%与57%,P<0.05),且观察A组与观察B组对比差异无统计学意义(92%与88%,P>0.05);3组患者治疗前左心室射血分数(LVEF)、左心室收缩末期容积(LVESV)、左心室舒张末期容积(LVEDV)对比差异无统计学意义(P>0.05),治疗后,3组患者LVEF升高,观察B组高于观察A组及对照组(F=3.566,P<0.05),LVESV、LVEDV降低,观察B组低于观察A组及对照组(F=2.133、4.447,P<0.05);3组患者治疗前心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)、肌酸激酶(CK)对比差异无统计学意义(P>0.05),治疗后,3组患者cTnI、CK-MB、CK降低,观察B组低于观察A组及对照组(F=21.807、5.158、5.472,P<0.05);3组患者治疗前CEA、MFG-E8对比差异无统计学意义(P>0.05),治疗后,3组患者MFG-E8升高,观察B组高于观察A组及对照组(F=3.237,P<0.05),CEA降低,观察B组低于观察A组及对照组(F=19.096,P<0.05);3组患者不良反应发生率对比差异无统计学意义(7%与12%与8%,χ^(2)=0.213,P=0.644)。结论对介入治疗后的心肌梗死患者无论是采取诺欣妥联合阿托伐他汀治疗还是SGLT2联合阿托伐他汀均能够提升患者临床疗效,但采取SGLT2联合阿托伐他汀治疗能够进一步提升患者心功能,降低心肌损伤,促进血管重建,降低炎症反应,且安全性较高。

从空肠AQP3、GLUT1的表达变化探讨脾气虚、脾阳虚证的机理

目的:通过分析脾气虚、脾阳虚证模型大鼠空肠组织中水通道蛋白3、葡萄糖转运体1基因及蛋白的表达变化,从分子生物学角度,探讨空肠组织中AQP3及GLUT1与脾气虚、脾阳虚证之间的关系,为研究脾气虚、脾阳虚证分子机制提供新思路。方法:动物随机分为对照组、脾气虚组和脾阳虚组,复合因素造模;观察大鼠一般体征,运用Realtime PCR结合Western blot方法检测大鼠AQP3、GLUT1基因及蛋白表达变化。结果:脾气虚、脾阳虚模型大鼠下空肠组织中的AQP3、GLUT1基因及蛋白表达较对照组均有显著降低(P<0.01);阳虚组表达较气虚组也有显著降低(P<0.01)。结论:脾气虚、脾阳虚证状态下大鼠空肠AQP3、GLUT1表达下调,导致对水分和葡萄糖的吸收出现障碍,可能与脾气虚、脾阳虚证的发病机制有关。

Lactate Promotes Cancer Stem-like Property of Oral Sequamous Cell Carcinoma

Accumulation of lactate in tumor has been linked to poor prognosis of oral squamous cell carcinoma (OSCC), but the underlying mechanism remained largely uncertain. Previous studies have suggested that presence of cancer stem cells (CSCs) closely correlated with cellular malignancy of OSCC. Here, using 3D organoid culture model, we investigated whether lactate promoted CSCs phenotype in primary OSCC cells. We generated organoids using fresh OSCC specimens and verified that organoids recapitulated histopathology and cellular heterogeneity of parental tumor;Organoids were then transfected with a Wnt reporter to visualize Wnt activity. The sphere forming assay demonstrated that high Wnt activity functionally designated CSCs population in OSCC cells. Further investigations indicated that lactate treatment promoted Wnt activity and increased the expression of CSCs (i.e. CD133^+ cells) in organoids. Moreover, silencing monocarboxylate transporter 1 (MCT1), the prominent path for lactate uptake in human tumor with siRNA significantly impaired organoid forming capacity of OSCC cells. Together, our study demonstrated that lactate can promote CSCs phenotype of OSCC,and MCT1 may be a therapeutic target against OSCC growth.

IL-1β对大鼠腹膜间皮细胞葡萄糖转运蛋白1表达的影响

目的:研究白介素1β(Interleukin-1beta,IL-1β)对原代培养大鼠腹膜间皮细胞(PMCs)葡萄糖转运蛋白1(GLUT1)表达的影响,为防治腹透失超滤提供理论依据及方法。方法:胰蛋白酶消化法进行雄性Wistar大鼠PMCs的原代培养及传代,不同浓度IL-1β(0、1、10、50 ng/ml)作用不同时间(0、1、12、24、48小时),逆转录多聚酶链反应(RT-PCR)检测GLUT1的mRNA表达,Western blot检测GLUT1蛋白的表达,生化分析仪检测培养液内葡萄糖浓度的变化,以培养液内葡萄糖的减少量作为细胞对葡萄糖的净利用。结果:IL-1β以浓度及时间依赖方式促进GLUT1 mRNA及蛋白的表达(P<0.05),同时伴有葡萄糖向细胞内转运的增加,50 ng/ml IL-1刺激48小时后GLUT1 mRNA表达与对照组相比增加了近4倍(P<0.01)。结论:IL-1β可以使PMCs细胞GLUT-1表达和葡萄糖摄取增加,这为防治腹透相关腹膜纤维化及腹透失超滤提供了线索。

幼年性血管瘤中葡萄糖转运蛋白1及CD32的表达

目的 :研究幼年性血管瘤中葡萄糖转运蛋白 1(GLUT1)、CD32的表达及与其他血管肿瘤的差异。方法 :免疫组织化学SP法分别检测 2 6例幼年性血管瘤、2 8例化脓性肉芽肿、2 5例中间性血管内皮瘤、4例血管肉瘤、7例血管外皮瘤及 6例胎盘组织中GLUT1及CD32的表达。结果 :幼年性血管瘤及胎盘绒毛膜表达GLUT1及CD32 ,化脓性肉芽肿、中间性血管内皮瘤、血管肉瘤及血管外皮瘤GLUT1、CD32染色阴性。结论 :幼年性血管瘤与胎盘绒毛膜共同表达GLUT1及CD32 ,二者内皮的表型具有相似性 ,与其他血管肿瘤有所不同。

非小细胞肺癌组织中缺氧诱导因子1α、葡萄糖转运蛋白1及增殖细胞核抗原的表达及临床意义

目的探讨非小细胞肺癌(NSCLC)中缺氧诱导因子1α(HIF-1α)、葡萄糖转运蛋白1(Glut1)与增殖细胞核抗原(PCNA)的表达及其相关性,并探讨其临床意义。方法采用免疫组化法检测HIF-1α、Glut1及PCNA在55例NSCLC组织和20例肺良性病变对照组织中表达及与临床病理参数间的关系。结果 NSCLC组和对照组中HIF-1α阳性率分别为76.36%(42/55)、15.00%(3/20),差异有高度统计学意义(P<0.01)。两组Glut1阳性表达率分别为85.45%(47/55)、25.00%(5/20),差异有高度统计学意义(P<0.01)。HIF-1α表达与TNM分期、淋巴结转移有关(均P<0.05);Glut1表达与病理类型、TNM分期、淋巴结转移有关(均P<0.05)。HIF-1α与Glut1表达呈正相关(r=0.598,P<0.01)。PCNA在NSCLC组中的表达[(75.00±21.99)%]明显高于对照组[(26.75±10.55)%](P<0.01)。HIF-1α、Glut1的表达与PCNA均呈正相关(r=0.514,P<0.01;r=0.608,P<0.01)。结论 NSCLC中HIF-1α、Glut1及PCNA过表达与NSCLC发生发展关系密切,联合检测三者有助于判断NSCLC临床分期及评估预后。

葡萄糖转运蛋白1和磷脂结合蛋白-1在子宫内膜癌中的表达及意义

背景与目的:探讨葡萄糖转运蛋白1(GLUT1)和磷脂结合蛋白-1(Annexin-1)在子宫内膜癌组织中的表达情况及其与临床病理参数之间的关系。材料与方法:采用免疫组化S-P法检测65例子宫内膜癌、27例非典型增生和21例增生期子宫内膜组织中GLUT1和Annexin-1的表达。结果:在增生期子宫内膜、非典型增生、子宫内膜癌的GLUT1阳性表达率分别为28.6%、59.3%、81.5%,呈递增趋势,组间两两比较,差异均具有统计学意义(P<0.05);Annexin-1阳性表达率分别为85.7%、55.6%、49.2%,呈下降趋势,其中子宫内膜癌与增生期子宫内膜比较差异有统计学意义(P<0.05)。GLUT1高表达与子宫内膜癌的组织分级、肌层浸润深度有关(P<0.05),与病理分期、淋巴结是否转移、组织学类型无关(P>0.05);Annexin-1低表达与上述的临床病理参数皆无关(P>0.05)。子宫内膜癌中GLUT1与Annexin-1呈负性相关(r=-0.540,P=0.000)。结论:Annexin-1低表达和GLUT1高表达可能对子宫内膜癌的发生和发展具有促进作用,二者对子宫内膜癌早期诊断和预后预测有一定意义。

抑制葡萄糖转运蛋白1表达可降低神经母细胞瘤细胞的增殖、侵袭和迁移能力

目的研究抑制神经母细胞瘤细胞中葡萄糖转运蛋白1(GLUT1)的表达对肿瘤细胞增殖和侵袭迁移能力的影响。方法运用特异性的小分子抑制剂WZB117抑制神经母细胞瘤细胞中GLUT1的表达,实时定量PCR检测GLUT1 mRNA水平表达,Western blot法检测其蛋白水平表达,CCK-8法检测细胞增殖能力,TranswellTM侵袭、迁移实验分别检测细胞侵袭、迁移能力。结果 WZB117作用于细胞后,GLUT1 mRNA水平增高,蛋白水平降低;细胞增殖受到抑制,细胞侵袭和迁移能力降低。结论抑制神经母细胞瘤细胞中GLUT1的表达能减弱肿瘤细胞恶性生物学行为。

Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent

Iron plays a key role in Parkinson＇s disease （PD）. Increased iron content of the substantia nigra （SN） has been found in PD patients, and divalent metal transporter 1 （DMT1） has been shown to be up-regulated in the SN of both MPTP-induced PD models and PD patients. However, the mechanisms underlying DMT1 up-regulation are largely unknown. In the present study, we observed that in the SN of 6-hydroxydopamine （6-OHDA）-induced PD rats, DMT1 with the iron responsive element （IRE, DMTI＋IRE）, but not DMT1 without IRE （DMTI-IRE）, was up- regulated, suggesting that increased DMTI＋IRE expression might account for nigral iron accumulation in PD rats. This possibility was further assessed in an in vitro study using 6-OHDA-treated and DMTl＋IRE-over-expressing MES23.5 cells. In 6-OHDA-treated MES23.5 cells, increased iron regulatory protein （IRP） 1 and IRP2 expression was observed, while silencing of IRPs dramatically diminished 6-OHDA-indueed DMTI＋IRE up-regulation. Pre- treatment with N-acetyl-L-cysteine fully suppressed IRPs up-regulation by inhibition of 6-OHDA-indueed oxidative stress. Increased DMTI＋IRE expression resulted in increased iron influx by MES23.5 cells. Our data provide direct evidence that DMTI＋IRE up-regulation can account for IRE/IRP-dependent 6-OHDA-induced iron accumulation initiated by 6-OHDA-induced intracellular oxidative stress and that increased levels of intracellular iron result in ag- gravated oxidative stress. The results of this study provide novel evidence supporting the use of anti-oxidants in the treatment of PD, with the goal of inhibiting iron accumulation by regulation of DMT1 expression.

胃癌中葡萄糖转运蛋白1、缺氧诱导因子-1α的表达及临床意义

目的:探讨葡萄糖转运蛋白1(glucosetransporter1, Glut1)和缺氧诱导因子-1α(hypoxia inducible factor-1 alpha, HIF-1α)的基因产物的表达及其临床意义。方法应用免疫组织化学EnvisionTM二步法检测120例胃癌和50例癌旁正常胃组织(距癌灶5 cm以上)中Glut1蛋白、HIF-1α的表达。结果 HIF-1α、Glut1在120例胃癌和50例癌旁组织中的阳性表达率分别为70%、69%和16%、18%,差异有统计学意义(<0.01)。胃癌组织中,HIF-1α的阳性表达与胃癌的临床分期、组织分型及淋巴结转移有关(<0.01)。Glut1的阳性表达与胃癌的临床分期、组织分型、组织学分级及淋巴结转移有关(<0.05)。HIF-1α与Glut1表达程度呈正相关(r1=0.62,<0.01)。结论 HIF-1α、Glutl的阳性表达可以作为胃癌侵袭转移潜能的生物学指标,且这些指标的表达对于临床早期干预治疗具有重要的指导意义。

Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload

Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer＇s dis- ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer＇s disease patients. An APPs,~JPSI^E9 double transgenic mouse model of Alzheimer＇s disease was used. The intragas- tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer＇s disease. These com- pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer＇s disease.

Role of alcohol in the regulation of iron metabolism

Patients with alcoholic liver disease frequently exhibit increased body iron stores, as reflected by elevated serum iron indices (transferrin saturation, ferritin) and hepatic iron concentration. Even mild to moderate alcohol consumption has been shown to increase the prevalence of iron overload. Moreover, increased hepatic iron content is associated with greater mortality from alcoholic cirrhosis, suggesting a pathogenic role for iron in alcoholic liver disease. Alcohol increases the severity of disease in patients with genetic hemochromatosis, an iron overload disorder common in the Caucasian population. Both iron and alcohol individually cause oxidative stress and lipid peroxidation, which culminates in liver injury. Despite these observations, the underlying mechanisms of iron accumulation and the source of the excess iron observed in alcoholic liver disease remain unclear. Over the last decade, several novel iron-regulatory proteins have been identified and these have greatly enhanced our understanding of iron metabolism. For example, hepcidin, a circulatory antimicrobial peptide synthesized by the hepatocytes of the liver is now known to play a central role in the regulation of iron homeostasis. This review attempts to describe the interaction of alcohol and iron-regulatory molecules. Understanding these molecular mechanisms is of considerable clinical importance because both alcoholic liver disease and genetic hemochromatosis are common diseases, in which alcohol and iron appear to act synergistically to cause liver injury.

Divalent metal transporter 1 expression and iron deposition in the substantia nigra of a rat model of Parkinson's disease

Extensive iron deposition has been observed in the midbrain substantia nigra （SN） of Parkinson＇s disease （PD） patients, but the mechanisms of iron deposition in the SN remain poorly understood. The present study investigated the relationship between dopaminergic neuronal damage, iron content changes, and divalent metal transporter 1 （DMT1） in the midbrain SN of PD rats to explore the relationship between time of iron deposition and DMT1 expression. Frozen midbrain SN sections from model rats were stained with Perls＇ iron. Results showed massive loss of tyrosine hydroxylase （TH）-positive cells in the SN and increased DMT1 expression in model group rats. No obvious iron deposition was observed in the SN during early stages after damage, but significant iron deposition was detected at 8 weeks post-injury. Results demonstrate that the loss of TH-positive cells in the SN appeared simultaneously with increased DMT1 expression. Extensive iron deposition occurred at 8 weeks post injury, which could be regarded as an early time window of iron deposition.

Effects of electroacupuncture on microcirculatory blood flow and glucose transporter function in the hippocampus

Nerve cell metabolism in post brain ischemia depends on increased microcirculation perfusion and transport function of microvascular endothelial cells. In the present study, a rat model of middle cerebral artery occlusion was established to investigate the influence of electroacupuncture （EA） on hippocampal CA1 cerebral blood flow and glucose transporter 1 （GLUT1） expression in the microvascular endothelial cells. Following EA at Neiguan （PC 6）, the cerebral blood flow in the ischemic hippocampal CA1 region was significantly elevated, the number and microvascular integrated absorbance of the GLUTl-positive cells were significantly increased, nerve cell damage was ameliorated, and GLUT1 protein expression in the ischemic hippocampus was significantly increased. Results demonstrate that EA increased the cerebral blood flow of the hippocampal CA1 region and improved the glucose transport function, thereby attenuating neuronal injuries.