Low-density lipoprotein receptor-related protein 2(LRP2)is required for lipid export in the midgut of the migratory locust,Locusta migratoria

Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.

X连锁迟发性脊椎骨骺发育不良家系TRAPPC2基因缺失突变的高通量测序分析

目的·研究一个X连锁迟发性脊椎骨骺发育不良(spondyloepiphyseal dysplasia tarda,SEDT)家系的致病基因及突变类型。方法·提取一个SEDT家系6名成员外周血基因组DNA。应用Clearseq遗传性疾病试剂盒靶向捕获先证者基因组样本中与罕见遗传性疾病相关的致病区域,并进行高通量测序,过滤去除高频突变。采用外显子组隐马尔科夫模型(exome hidden Markov model,XHMM)分析拷贝数变异(copy number variant,CNV),并进一步对6名家系成员基因缺失片段的拷贝数进行实时定量PCR分析。结果·高通量测序分析结果显示,先证者X染色体存在2.5 kb缺失(chrX:13732385~13734927),该区域覆盖转运蛋白复合体亚单位2(transport protein particle complex subunit 2,TRAPPC2)基因的第4~6个外显子。定量PCR结果证实先证者及其表哥均存在该缺失,先证者母亲为杂合缺失,先证者父亲、姐姐和表型正常的舅舅拷贝数均正常。结论·TRAPPC2基因第4~6个外显子片段的缺失为SEDT的致病性突变;同时高通量测序分析中运用XHMM算法可检测到致病基因多个外显子的缺失。

冠心病患者ABCG1、ANGPTL2启动子区甲基化与心力衰竭发生的关系研究

目的分析冠状动脉粥样硬化性心脏病(冠心病)患者三磷酸腺苷结合盒转运蛋白G1(ABCG1)、血管生成素样蛋白2(ANGPTL2)启动子区甲基化与心力衰竭(心衰)发生的关系。方法选取2020年3月至2022年3月于湖南省第二人民医院收治的冠心病患者120例。根据是否发生心衰,将患者分为合并心衰组(n=26)和不合并心衰组(n=94)。采用全自动生化仪检测血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)。采用心脏超声检查患者左室射血分数(LVEF)、左心室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)水平。特异性PCR检测ABCG1和ANGPTL2基因甲基化。采用实时荧光定量聚合酶链反应检测ABCG1和ANGPTL2基因mRNA表达水平。Logistic回归分析探讨影响冠心病患者发生心衰的因素。结果两组患者LDL-C、LVEF、LVEDD、LVESD、ABCG1、ANGPTL2基因启动子区甲基化等方面比较,差异具有统计学意义(P<0.05)。LVESD、LVEF、ABCG1甲基化和ANGPTL2甲基化是冠心病患者发生心衰的危险因素。ABCG1甲基化、ANGPLT2甲基化患者中LVESD水平均高于未甲基化患者(P<0.05)。ABCG1甲基化、ANGPLT2甲基化患者中LVEF水平均低于未甲基化患者(P<0.05)。合并组ABCG1、ANGPTL2基因甲基化的患者mRNA的表达量明显低于非甲基化患者(P<0.05)。结论ABCG1和ANGPTL2基因甲基化是冠心病患者发生心衰的危险因素,检测上述两基因甲基化状态可为诊治冠心病心衰提供理论支持。

SGLT2i对糖尿病心肌保护作用及机制研究进展

钠-葡萄糖协同转运蛋白-2抑制剂(SGLT2i)是新型的降糖药物,通过其独特的降糖机制来调整患者的血糖。目前的很多研究发现SGLT2i在降低血糖的同时也能使患者的心功能受益,但是目前其作用机制尚未完全明确,本文对其相关机制的研究进展进行综述。

MiR-219a-5p exerts a protective function in a mouse model of myocardial infarction

Background:Myocardial infarction(MI)is known worldwide for its important disabling features,including myocarditis and cardiomyocyte apoptosis.It is believed that microRNA(miRNA)has a role in the cellular processes of apoptosis and myocarditis,and miR-219a-5p has been found to suppress the inflammatory response.However,unknown is the precise mechanism by which miR-219a-5p contributes to MI.Methods:We measured the expression of miR-219a-5p and evaluated its effects on target proteins,inflammatory factors,and apoptosis in a mouse model of MI.Echocardiography was utilized to examine the MI clinical index,and triphenyl tetrazolium chloride staining was employed to analyze the infarcted region.Enzyme-linked immunosorbent assay and Western blotting measured serum and molecular markers in heart tissues.To quantify the association with miR-219a-5p and ATPase sarcoplasmic/endoplasmic reticulum Ca^(2+) transporting 2(ATP2A2),the luciferase activity assay and Pearson’s correlation analysis were employed.Results:MiR-219a-5p exhibited low expression in a mouse model of MI,and its amplification prevented both apoptotic and inflammatory reactions.Specifically,miR-219a-5p targeted ATP2A2.Conclusion:In a mouse model of MI,miR-219a-5p exerted a potent protective effect via direct targeting of ATP2A2.

Tale of two kinases:Protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ in pre-diabetic cardiomyopathy

Metabolic syndrome is a pre-diabetic state characterized by several biochemical and physiological alterations,including insulin resistance,visceral fat accumulation,and dyslipidemias,which increase the risk for developing cardiovascular disease.Metabolic syndrome is associated with augmented sympathetic tone,which could account for the etiology of pre-diabetic cardiomyopathy.This review summarizes the current knowledge of the pathophysiological consequences of enhanced and sustainedβ-adrenergic response in pre-diabetes,focusing on cardiac dysfunction reported in diet-induced experimental models of pre-diabetic cardiomyopathy.The research reviewed indicates that both protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ play important roles in functional responses mediated byβ1-adrenoceptors;therefore,alterations in the expression or function of these kinases can be deleterious.This review also outlines recent information on the role of protein kinase A and Ca^(2+)/calmodulin-dependent protein kinase Ⅱ in abnormal Ca^(2+)handling by cardiomyocytes from diet-induced models of pre-diabetic cardiomyopathy.

钠-葡萄糖共转运蛋白2抑制剂在老年2型糖尿病合并常见心血管疾病中的应用进展

老年2型糖尿病(T2DM)患者常有多病共存现象,而合并心血管疾病(CVD)最为常见,是其致残、致死的首要原因。钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)是一种新型降糖药物,其心血管保护作用受到广泛关注,在老年T2DM与CVD共病的治疗上展现出良好的前景。本文就SGLT2i在T2DM合并心力衰竭、高血压、动脉粥样硬化、心肌梗死等常见CVD中的应用研究进展作一综述。

乌贼墨对H_(22)癌细胞内Ca^(2+)浓度、细胞核Ca^(2+)/Mg^(2+)-ATP酶活性及c-fos表达的影响

目的 :研究乌贼墨对H2 2 癌细胞内Ca2 +浓度、细胞核Ca2 +/Mg2 + ATP酶活性及c fos表达的影响。方法 :利用Fura 2 /AM荧光探针和免疫组织化学方法 ,测定乌贼墨对H2 2 癌细胞内Ca2 +浓度、细胞核Ca2 +/Mg2 + ATP酶活性及c fos表达的变化。结果 :乌贼墨使H2 2 癌细胞内Ca2 +浓度降低了 69%和79 % ,细胞核Ca2 +/Mg2 + ATP酶活性降低了 2 1%和 37% ,c fos表达明显减少。结论 :乌贼墨可能通过降低细胞内Ca2 +浓度 ,影响细胞核上Ca2 +依赖性Ca2 +/Mg2 + ATP酶活性 ,减少了Ca2 +向细胞核内的转运 ,减弱了Ca2 +对c fos表达的促进作用 ,抑制了细胞的分裂增殖。

血清LCN2、Apelin-17水平与急性缺血性卒中患者侧支循环形成的关系

目的探讨血清脂质运载蛋白2(LCN2)、血管紧张素Ⅱ受体样1内源性配体17(Apelin-17)水平与急性缺血性卒中(AIS)患者侧支循环形成的关系。方法选取181例AIS患者为AIS组,根据侧支循环形成情况分为不良组69例和良好组112例,另选取60例体检健康者为对照组。采用酶联免疫吸附法检测血清LCN2、Apelin-17。采用多因素Logistic回归分析AIS患者侧支循环形成不良的影响因素,采用受试者工作特征(ROC)曲线分析血清LCN2、Apelin-17水平对AIS患者侧支循环形成不良的预测价值。结果与对照组比较,AIS组血清LCN2水平升高,Apelin-17水平降低(P均<0.05)。多因素Logistic回归分析显示,年龄大(OR=1.048,95%CI:1.010~1.087)、高血压(OR=2.052,95%CI:1.034~4.072)、糖尿病(OR=2.127,95%CI:1.115~4.056)、美国国立卫生研究院卒中量表评分高(OR=1.166,95%CI:1.049~1.296)、LCN2水平高(OR=1.225,95%CI:1.127~1.331)为AIS患者侧支循环形成不良的独立危险因素,Apelin-17水平高(OR=0.947,95%CI:0.926~0.969)为独立保护因素(P均<0.05)。ROC曲线分析显示,血清LCN2联合Apelin-17(AUC=0.861,95%CI:0.802~0.908)预测AIS患者侧支循环形成不良的曲线下面积(AUC)大于LCN2(AUC=0.764,95%CI:0.696~0.824)、Apelin-17(AUC=0.765,95%CI:0.697~0.825)单独预测(P均<0.05)。结论血清LCN2水平升高和Apelin-17水平降低与AIS患者侧支循环形成不良独立相关,血清LCN2联合Apelin-17预测AIS患者侧支循环形成不良的价值较高。

Transepithelial transport of putrescine across monolayers of the human intestinal epithelial cell line, Caco-2

AIM: To study the transepithelial transport characteristics of the polyamine putrescine in human intestinal Caco-2 cell monolayers to elucidate the mechanisms of the putrescine intestinal absorption. METHODS: The transepithelial transport and the cellular accumulation of putrescine was measured using Caco-2 cell monolayers grown on permeable filters. RESULTS: Transepithelial transport of putrescine in physiological concentrations (】 0.5 mM) from the apical to basolateral side was linear. Intracellular accumulation of putrescine was higher in confluent than in fully differentiated Caco-2 cells, but still negligible (less than 0.5%) of the overall transport across the monolayers in apical to basolateral direction.EGF enhanced putrescine accumulation in Caco-2 cells by four fold, as well as putrescine conversion to spermidine and spermine by enhancing the activity of S adenosylmethionine decarboxylase. However, EGF did not have any significant influence on putrescine flux across the Caco-2 cell monolayers. Excretion of putrescine from Caco-2 cells into the basolateral medium did not exceed 50 picomoles, while putrescine passive flux from the apical to the basolateral chamber, contributed hundreds of micromoles polyamines to the basolateral chamber. CONCLUSION :Transepithelial transport of putrescine across Caco2 cell monolayers occurs in passive diffusion, and is not influenced when epithelial cells are stimulated to proliferate by a potent mitogen such as EGF.

Collapsin response mediator protein-2 plays a major protective role in acute axonal degeneration

Axonal degeneration is a key pathological feature in many neurological diseases. It often leads to persistent deficits due to the inability of axons to regenerate in the central nervous system. Therefore therapeutic approaches should optimally both attenuate axonal degeneration and foster axonal regeneration. Compelling evidence suggests that collapsin response mediator protein-2（CRMP2） might be a molecular target fulfilling these requirements. In this mini-review, we give a compact overview of the known functions of CRMP2 and its molecular interactors in neurite outgrowth and in neurodegenerative conditions. Moreover, we discuss in detail our recent findings on the role of CRMP2 in acute axonal degeneration in the optic nerve. We found that the calcium influx induced by the lesion activates the protease calpain which cleaves CRMP2, leading to impairment of axonal transport. Both calpain inhibition and CRMP2 overexpression effectively protected the proximal axons against acute axonal degeneration. Taken together, CRMP2 is further characterized as a central molecular player in acute axonal degeneration and thus evolves as a promising therapeutic target to both counteract axonal degeneration and foster axonal regeneration in neurodegenerative and neurotraumatic diseases.

基于OCT2、MRP2探讨加味生脉饮对Lewis肺癌小鼠顺铂化疗的增效减毒机制

【目的】观察加味生脉饮对顺铂化疗Lewis肺癌小鼠有机阳离子转运体2(OCT2)、多药耐药相关蛋白2(MRP2)的影响,探讨其对Lewis肺癌小鼠顺铂化疗的增效减毒机制。【方法】采用腋窝皮下接种Lewis肺癌细胞(LLC)构建肺癌移植瘤小鼠模型,造模成功后随机分为对照组、顺铂组、联合组(顺铂联合加味生脉饮)和生脉饮组,每组7只小鼠,给药14 d。观察4组小鼠一般状态、肿瘤生长情况,肿瘤、肾脏组织病理学以及血清尿素氮(BUN)、肌酐(Cr)浓度。通过免疫组织化学染色(IHC)和Western Blot的方法检测OCT2、MRP2蛋白表达情况,并使用高效液相色谱串联质谱(HPLC-MS/MS)法测定肾脏和肿瘤组织中顺铂含量。【结果】(1)给药结束后,各组小鼠体质量均有下降,顺铂组下降幅度最大,顺铂组体质量变化显著高于联合组、生脉饮组(P<0.05),生脉饮组和联合组小鼠一般状态均优于对照组和顺铂组。(2)干预结束时,顺铂组肿瘤体积和质量小于生脉饮组和对照组,联合组肿瘤体积和质量显著小于顺铂组(P<0.05)。(3)组织病理学结果显示:生脉饮组、对照组肿瘤细胞结构清晰,细胞形态正常;顺铂组与联合组可见肿瘤细胞坏死,肿瘤细胞边缘模糊,联合组肿瘤细胞坏死面积更大。生脉饮组、对照组肾脏细胞形态正常;联合组肾脏细胞损伤较轻,无明显病变;顺铂组肾组织明显病变,肾小管上皮细胞边缘模糊。(4)顺铂组小鼠血清BUN、Cr水平显著高于其他3组(P<0.05)。(5)顺铂组肾脏组织OCT2表达相比对照组显著增加,联合组OCT2表达相比顺铂组显著降低(均P<0.05);顺铂组肿瘤组织MRP2表达相比对照组显著增加,联合组MRP2表达相比顺铂组显著降低(均P<0.05)。(6)联合组肿瘤组织中顺铂含量显著高于顺铂组,联合组肾脏组织中顺铂含量显著低于顺铂组(均P<0.05)。【结论】OCT2、MRP2在顺铂肾脏毒性与耐药性中起重要的调控作用,加味生脉饮可能通过抑制肾脏中OCT2与肿瘤细胞中MRP2的蛋白表达,降低了顺铂治疗的肾脏毒性,提高了顺铂的抗肿瘤效果。

社区获得性肺炎患者血清Ang-2、NGAL的临床意义

目的 探讨重症社区获得性肺炎(severe communityacquired pneumonia,SCAP)患者血清中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase associated lipids transport proteins,NGAL)、血管生成素-2(angiogenin-2,Ang-2)水平变化,分析其与SCAP的相关性。方法 纳入2020年1月—2022年1月临床确诊的60例SCAP患者作为SCAP组,60例非重症社区获得性肺炎作为CAP组。对比两组血氧饱和度、氧分压、二氧化碳分压、氧合指数(oxygenation index,OI)、心率、呼吸、C反应蛋白(C-reactive protein,CRP)、降钙素原(procalcitonin,PCT)、白细胞计数(white blood cell count,WBC)、中性粒细胞百分比、血小板计数(blood platelet count,PLT)、急性生理与慢性健康(acute physiology and chronic health evaluationⅡ,APACHEⅡ)评分、CURB-65(confusion uremia respiratory rate blood pressure-65)评分的差异,采用酶联免疫吸附实验检测血清NGAL、Ang-2水平。结果 (1)与CAP组比较,SCAP组血氧饱和度、氧分压、OI、PLT均明显下降,而二氧化碳分压、心率、呼吸、CRP、PCT、WBC、中性粒细胞百分比、APACHEⅡ评分、CURB-65评分均明显升高,差异有统计学意义(P <0.01)。(2)SCAP组患者血清NGAL、Ang-2水平均较CAP组明显升高,差异有统计学意义(P <0.01)。(3)Pearson相关分析显示,血清NGAL、Ang-2均与CRP、PCT、WBC、APACHEⅡ评分、CURB-65评分呈正相关,而与OI、PLT呈负相关,差异有统计学意义(P <0.05)。(4)Logistic回归分析显示,NGAL、Ang-2、CRP、PCT、APACHEⅡ评分、CURB-65评分为SCAP的独立危险因素,而OI为SCAP保护性因素。结论 SCAP患者血清NGAL、Ang-2水平明显升高,NGAL、Ang-2可能是SCAP的危险因素。

SGLT2抑制剂与GLP-1受体激动剂对2型糖尿病患者心血管影响的研究

2型糖尿病(T2DM)患者容易并发微血管和大血管病变,是心血管疾病发生的独立危险因素。钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂与胰高血糖素(GLP)-1受体激动剂都已明确对T2DM患者心血管有益处,但是又有不同的优缺点,本文就这两种药物对T2DM患者心血管的影响作一综述。

急性脑梗死患者血清FGL2和TSPO表达水平及其与神经功能缺损程度和预后的相关性研究

目的 检测急性脑梗死(acute cerebral infarct, ACI)患者血清纤维蛋白原样蛋白2(FGL2)和转运蛋白(TSPO)水平,探讨二者与患者神经功能缺损程度及预后的关系。方法 选取2020年8月~2021年8月河北省邯郸市邯钢医院收治的110例急性脑梗死患者为研究对象,另取同期体检健康者90例为对照组。酶联免疫吸附法检测血清FGL2和TSPO水平;美国国立卫生研究院卒中量表(NIHSS)评估患者神经功能缺损程度,采用Spearman等级相关分析急性脑梗死患者神经功能缺损程度与血清FGL2和TSPO水平的相关性;根据急性脑梗死患者预后情况将其分为预后良好组(n=76)和预后不良组(n=34),受试者工作特征(ROC)曲线分析血清FGL2和TSPO对急性脑梗死患者预后的预测效能。结果 与对照组比较,急性脑梗死患者血清FGL2水平(231.52±41.29 ng/ml vs 125.26±24.16 ng/ml)和TSPO水平(6.28±1.05 ng/L vs 3.54±0.74 ng/L)升高,差异均有统计学意义(t=21.573,20.872,均P <0.05)。与轻度组比较,中度组血清FGL2(236.63±42.49ng/ml vs196.62±36.61ng/ml),TSPO(6.36±1.04ng/L vs 4.84±0.87ng/L)水平升高,与中度组比较,重度组血清FGL2(275.20±50.25ng/ml vs 236.63±42.49ng/ml),TSPO(8.26±1.32ng/L vs 6.36±1.04ng/L)水平升高,差异均有统计学意义(t=4.549,7.153;3.432,6.640,均P <0.05)。Spearman相关性分析显示血清FGL2,TSPO水平与神经功能缺损程度呈正相关(r=0.514,0.495,均P <0.05)。与预后良好组比较,预后不良组血清FGL2水平(287.75±43.81 ng/ml vs 206.36±40.16 ng/ml)和TSPO水平(7.83±1.80 ng/L vs 5.58±0.72 ng/L)升高,差异均有统计学意义(t=9.549,9.386,均P<0.05)。血清FGL2,TSPO预测急性脑梗死患者预后不良的曲线下面积(AUC)分别为0.926,0.825,联合预测的AUC为0.975,优于各指标单独预测(Z=2.621,3.100,均P <0.05)。结论 急性脑梗死患者血清FGL2和TSPO水平增高,与神经功能缺损程度呈正相关,对患者的预后状况具有较高的预测效能,为临床的合理干预和改善患者预后提供依据。

芒果苷改善2型糖尿病大鼠糖脂代谢紊乱的作用及机制研究

为探讨芒果苷改善大鼠2型糖尿病(type 2 diabetes mellitus,T2DM)糖脂代谢紊乱的作用及潜在机制,将T2DM大鼠随机分为模型对照组、二甲双胍组(100 mg/kg)及芒果苷低、中、高剂量组(50、100、200 mg/kg),另设正常对照组,10只/组;灌胃给药,1次/d,持续8周。评价空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS)、胰岛素抵抗指数(insulin resistance index,HOMA-IR)及血清游离脂肪酸(free fatty acid,FFA)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)等指标,并检测肝组织谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、过氧化氢酶(catalase,CAT)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)及胰岛素受体底物1(insulin receptor substrate 1,IRS-1)/蛋白激酶B(protein kinase B,Akt)/葡萄糖转运蛋白4(glucose transporter 4,Glut4)信号通路相关m RNA和蛋白表达。结果发现,芒果苷可以改善T2DM大鼠毛色、活动及精神等一般状态,减缓体重下降趋势;与模型对照组比较,经芒果苷治疗8周后,各治疗组大鼠FBG、FINS、HOMA-IR及血清FFA、TG、TC含量均显著或极显著降低(P<0.05,P<0.01);各治疗组大鼠肝组织GSH-Px、CAT、SOD活力显著或极显著高于模型对照组(P<0.05,P<0.01),而MDA含量极显著降低(P<0.01);与模型对照组比较,芒果苷低、中、高剂量组大鼠肝组织IRS-1 mRNA表达无显著差异(P>0.05),Akt、Glut4 mRNA及p-IRS-1(Tyr)、Akt、Glut4蛋白表达显著或极显著增加(P<0.05,P<0.01),而p-IRS-1(Ser)蛋白表达显著或极显著降低(P<0.05,P<0.01)。上述结果表明,芒果苷具有改善T2DM大鼠糖脂代谢紊乱的作用,该作用与抗氧化应激及调节IRS-1/Akt/Glut4信号通路有关。

Anti-diabetic potential of apigenin,luteolin,and baicalein via partially activating PI3K/Akt/GLUT-4 signaling pathways in insulin-resistant HepG2 cells

Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.

胰高糖素样肽-1受体激动剂联合钠-葡萄糖共转运蛋白2抑制剂在2型糖尿病中的应用

糖尿病目前是严重威胁人类健康的世界性重大公共卫生问题。因长期血糖控制不佳从而导致各种并发症,严重影响着患者的生活质量。糖尿病的治疗不单单在于血糖的控制,最重要的是并发症的治疗和预防。近年来,对降糖药物的探索中,胰高血糖素样肽-1受体激动剂联合钠葡萄糖协同转运蛋白2抑制剂治疗2型糖尿病且在心血管、肾脏及其他代谢方面有诸多益处。本文综述了胰高血糖素样肽-1受体激动剂联合钠葡萄糖协同转运蛋白2抑制剂在治疗2型糖尿病的应用。

三阴性乳腺癌组织中YAP、CD155、KPNA2的表达及意义

目的探究三阴性乳腺癌(TNBC)组织中YES相关蛋白(YAP)、CD155、核转运蛋白基因2(KPNA2)的表达及意义。方法选取2016年1月至2022年10月洛阳市妇幼保健院和驻马店市中医院收治的74例TNBC患者为研究对象,取患者手术切除癌组织和癌旁正常组织分为TNBC组与癌旁组织组。比较各组YAP、CD155、KPNA2表达的差异,并分析YAP、CD155、KPNA2表达与TNBC患者临床病理特征相关。对患者进行随访记录TNBC患者疾病进展状况,并分析YAP、CD155、KPNA2表达与TNBC患者进展状态的关系。结果TNBC组YAP阳性表达、CD155阳性表达、KPNA2阳性表达>癌旁组织组(P<0.05)。YAP阳性表达与TNBC患者肿瘤直径、分化程度、TNM分期存在相关(P<0.05),CD155阳性表达与肿瘤直径、分化程度、淋巴结转移存在相关(P<0.05),KPNA2阳性表达与分化程度、淋巴结转移存在相关(P<0.05)。随访时间截至2023年4月,74例TNBC患者进中发生疾病进展41例,无进展33例。TNBC组YAP阳性表达、CD155阳性表达、KPNA2阳性表达与进展状态存在相关(P<0.05)。Kaplan-Meier生存曲线显示,74例患者总无进展生存时间为[35.5(22.75,49.25)]个月,且YAP阳性、CD155阳性、KPNA2阳性无进展生存率低于YAP阴性、CD155阴性、KPNA2阴性(P<0.05)。结论YAP、CD155、KPNA2在TNBC患者组织中高表达,与患者临床病理特征及预后相关密切。

ABCG2食管癌耐药细胞系Eca109/ABCG2的建立

目的探讨腺苷三磷酸结合转运蛋白G超家族成员2(ABCG2)在介导食管癌多药耐药中的作用。方法扩增ABCG2基因,与pcDNA3.1载体连接,构建pcDNA3.1-ABCG2重组质粒,转染Eca109细胞后用G418筛选稳定转染细胞。采用流式细胞术检测细胞内阿霉素的含量,评价细胞对药物的外排作用。MTT法检测阿霉素对Eca109/ABCG2、Eca109/pcDNA3.1、Eca109细胞生长的抑制作用,并计算半数抑制浓度(IC50)和细胞的耐药指数。采用Western blotting和RT-PCR法检测细胞中ABCG2蛋白及mRNA的表达量。结果成功建立转染ABCG2基因的Eca109/ABCG2细胞。Eca109/ABCG2细胞中ABCG2的mRNA和蛋白表达量升高。阿霉素对Eca109/ABCG2、Eca109/pcDNA3.1、Eca109细胞的IC50值分别为18.61±3.94、4.18±0.14、4.69±0.88μg/ml。Eca109/AB-CG2细胞对阿霉素的耐药指数为3.97,且外排阿霉素的作用增强。结论Eca109/ABCG2细胞具有ABCG2的耐药表型,能够稳定表达ABCG2蛋白,可作为研究ABCG2介导的多药耐药相关机制的细胞模型。