Sodium selenite may be not the optimal speciation as an effective therapy for arsenic-induced anxiety-/depression-like behavior

Major depressive disorder is a serious and prevalent neuropsychiatric disorder,affecting more than 350 million people worldwide.Here,sodium selenite(SS)was selected as the selenite supplement to improve the behavior in a mouse model of depression induced by As.SS may be not the optimal speciation for selenite supplementation and the source of the SS used in the study was not disclosed.There are many mouse models of depression and anxiety;however,in the current study,a classical mouse model of depression was not used.Thus,several questions still need to be further discussed.Taken together,the results indicate that SS may be not the optimal speciation as an effective therapy for As-induced anxiety-/depression-like behavior.

Change of choline compounds in sodium selenite-induced apoptosis of rats used as quantitative analysis by in vitro 9.4T MR spectroscopy

AIM: To study liver cell apoptosis caused by the toxicity of selenium and observe the alteration of choline compounds using in vitro 9.4T high resolution magnetic resonance spectroscopy. METHODS: Twenty male Wistar rats were randomly divided into two groups. The rats in the treatment group were intraperitoneally injected with sodium selenite and the control group with distilled water. All rats were sacrifi ced and the livers were dissected. 1H-MRS data were collected using in vitro 9.4T high resolution magnetic resonance spectrometer. Spectra were processed using XWINNMR and MestRe-c 4.3. HE and TUNEL staining was employed to detect and confi rm the change of liver cells. RESULTS: Good 1H-MR spectra of perchloric acid extract from liver tissue of rats were obtained. The conventional metabolites were detected and assigned. Concentrations of different ingredient choline compounds in treatment group vs control group were as follows: total choline compounds,5.08 ± 0.97 mmol/L vs 3.81 ± 1.16 mmol/L (P = 0.05); and free choline,1.07 ± 0.23 mmol/L vs 0.65 ± 0.20 mmol/L (P = 0.00). However,there was no statistical signif icance between the two groups. The hepatic sinus and cellular structure of hepatic cells in treatmentgroup were abnormal. Apoptosis of hepatic cells was confi rmed by TUNEL assay. CONCLUSION: High dose selenium compounds can cause the rat liver lesion and induce cell apoptosis in vivo. High resolution 1H-MRS in vitro can detect diversified metabolism. The changing trend for different ingredient of choline compounds is not completely the same at early period of apoptosis.

Redifferentiation of Human Gastric Cancer Cells Induced by Ascorbic Acid and Sodium Selenite

Objective To explore the effects and mechanisms of ascorbic acid (AA) and sodium selenite (SS) on growth inhibition and redifferentiation in human gastric cancer cells. Methods In the present study, trypan blue dye exclusion method was used to determine the cell growth curve and mitotic index, cell electrophoresis and colonogenic potential were used as the indexes of redifferentiation. In order to find out the mechanisms of redifferentiation, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were assayed, the content of malondialdehyde (MDA), reduced glutathione (GSH) and H2O2 were evaluated. Results After treatment with AA 3 mol/L + SS 2μmol/L, the growth rate and mitotic index of human gastric cancer cells (MGc-803) decreased remarkably. The indexes related with cell malignancy were alleviated. For example, cell surface charge was obviously decreased, the electrophoresis rate was dropped from 2.21 to 1.15μm·s-1·V-1·cm-1. The indexes related with cell redifferentiation were promoted. For example, the colonogenic potential was decreased to 93.5%. These results indicated that redifferentiation of human gastric cancer cells was successfully induced by AA + SS. The activities of SOD and GPX were significantly higher, while the activity of CAT was slower in treated group than that in the control. The content of MDA was slightly decreased, GSH was sharply decreased, and H2O2 content was dramatically increased. Conclusion These results indicated that combination of ascorbic acid and sodium selenite may induce the redifferentiation of human gastric cancer cells and inhibit cell growth by virtue of enhancing the activities of antioxidative enzymes and inducing the formation of H2O2, and altering the cell redox status. Combination of ascorbic acid and sodium selenite may be a potent anticancer agent for human gastric cancer.

Sodium selenite ameliorates dextran sulfate sodiuminduced chronic colitis in mice by decreasing Th1, Th17, and γδT and increasing CD4(+)CD25(+) regulatory T-cell responses

AIM To assess the effect of sodium selenite on the severity of dextran sulfate sodium(DSS)-induced colitis in C57BL/6 mice.METHODS Mice were randomly divided into four groups(n = 10/group): normal group, selenium(Se) group, chronic colitis group, and Se + chronic colitis group. The mice were sacrificed on day 26. Survival rates, clinical symptoms, colon length, and histological changes were determined. The percentages and absolute numbers of immune system cells in the lamina propria lymphocytes(LPL) of the colon, the expression of m RNA in colon tissue, and the concentrations of Th1, Th17, and Treg cytokines in LPL from the large intestine, were measured.RESULTS Se significantly ameliorated the symptoms of colitis and histological injury(P < 0.05 each), increasing the proportions of neutrophils and CD4+ CD25+ T cells(P < 0.05 each) and decreasing the proportions of γδT cells, CD4+, CD4+CD44+, and CD4+ CD69+ T cells in LPL(P < 0.05 each). Moreover, Se reduced the expression of IL-6, IFN-γ, IL-17 A, IL-21, T-bet, and RORγt(P < 0.05 each), but enhanced the expression of IL-10 and Foxp3(P < 0.05 each). CONCLUSION These results suggest that Se protects against DSSinduced chronic colitis perhaps by increasing the number of CD4(+)CD25(+) Tregs that suppress the secretion of proinflammatory cytokines and populations of Th1, Th17, and γδT cells.

Sodium selenite promotes neurological function recovery after spinal cord injury by inhibiting ferroptosis

Ferroptosis is a recently discovered form of iron-dependent cell death,which occurs during the pathological process of various central nervous system diseases or injuries,including secondary spinal cord injury.Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis.However,whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood.In this study,we injected sodium selenite(3μL,2.5μM)into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling.We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal.Furthermore,sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4,promoted the survival of neurons and oligodendrocytes,inhibited the proliferation of astrocytes,and promoted the recovery of locomotive function of rats with spinal cord injury.These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.

Comparison of the impact of epigallocatechin gallate and ellagic acid in an experimental cataract model induced by sodium selenite

AIM：To compare the potential protective effects of epigallocatechin gallate（EGCG） and ellagic acid（EA） in an experimental cataract model.●METHODS：Twenty-eight Spraque-Dawley rat pups were assigned into four groups.All the rats,except for those in the control group,were injected subcutaneously sodium selenite to induce experimental cataract on the postpartum ninth day,and between 10 th and 14 th days.Rats in the sham,EGCG,and EA groups were intraperitoneally administered 50 mg/（kg·d） saline solution,50 mg/（kg·d） EGCG and 200 mg/（kg·d） EA,respectively.The reduced glutathione（GSH） and malondialdehyde（MDA） levels,total antioxidant status（TAS） and total oxidant status（TOS） in lens supernatants were measured.RESULTS：The mean cataract gradings in EGCG and EA groups were found to be significantly lower than that in sham group（P〈0.001）.The mean GSH levels and TASs in EGCG and EA groups were significantly higher than that in sham group while mean MDA levels and TOSs in EGCG and EA groups were significantly lower than that in the sham group（P〈0.001）.CONCLUSION：EGCG and EA have protective effects on cataract development via the inhibition of oxidative stress.

Protective Role of C-Phycocyanin Against Secondary Changes During Sodium Selenite Mediated Cataractogenesis

Age related cataract is the leading cause of blindness associated with accumulation of oxidative stress in the eye lens.The present investigation reveals the rational of the beneficial effects of the natural compound C-phycocyanin(CPC)is beneficial when administered to rat pups to protect against the secondary effects of sodium selenite induced cataractogenesis.A single subcutaneous dose of sodium selenite(19 lmol/kg body weight)on the 10th day of postpartum is adequate to induce cataract in rat pups.Serum biochemical parameters,such as the level of electrolytes,mean activities of anti-oxidant enzymes i.e.superoxide dismutase,catalase and reduced glutathione were observed to be significantly altered during selenite induced cataractogenic process.Histopathological examination revealed signs of degradation of normal cell architecture in the liver,kidney and eye lens.Interestingly,the deleterious effects of sodium selenite toxicity were restored with the simultaneous treatment with C-PC.The results suggest that an administration of 200 mg/kg body weight of C-PC has the ability to prevent/alter the secondary changes reflected in the serum biochemical and histological modifications in rats exposed to sodium selenite.These results complement the beneficial role of C-PC of cyanobacterial origin as a efficacious anti-cataractogenic agent against sodium selenite toxicity.

Effect of Sodium Selenite-Chitosan Compound Preservative on Storability of Kumquats

[Objectives]To explore the effect of sodium selenite-chitosan compound preservative on storability of kumquats.[Methods]Under the condition of room temperature,fresh kumquats were coated with different concentrations of sodium selenite-chitosan compound preservative,respectively.[Results]Sodium selenite-chitosan compound preservative reduced the weight loss rate,delayed the decline of vitamin C,soluble solids,titratable acid and GSH contents,slowed down the accumulation of MDA,inhibited the increase of PPO activity,and increased to a certain extent the activity of SOD in fresh kumquats.[Conclusions]Sodium selenite-chitosan compound preservative maintained the quality and prolonged the shelf life of kumquats.The preservation effect of compound preservative composed of 4 mg/L sodium selenite and 8 g/L chitosan was the best.

外源硒对鸡腿菇菌丝生长及合成主要营养素的影响

以1株鸡腿菇菌株Cc-900为试材,采用平板培养和液体发酵培养的方法,研究不同浓度的外源硒对鸡腿菇菌株Cc-900的生长、富硒效果和菌丝合成蛋白质和多糖的影响,以期为富硒鸡腿菇的栽培和产品的开发提供参考依据。结果表明:鸡腿菇菌丝可耐受10 mg·kg^(-1)硒浓度的固体培养基和最大硒浓度为3 mg·L^(-1)的液体培养基,高浓度硒对菌丝活性损伤较大;当液体培养基中硒浓度为3 mg·L^(-1)时,菌丝干质量可达1.97 g·L^(-1),菌丝干粉的硒含量为38.24 mg·kg^(-1),其硒富集系数可达12.75,菌丝中粗蛋白和多糖含量分别为2.58%和3 081.82μg·g^(-1),发酵液中可溶性蛋白质和多糖含量分别为50.98μg·mL^(-1)和266.38μg·mL^(-1)。液体发酵培养中硒浓度在3 mg·L^(-1)以下可促进鸡腿菇菌丝的生长和硒的富集,同时促进菌丝中蛋白质的合成和释放,但会抑制菌丝中多糖的合成。

叶面喷施亚硒酸钠对金银花有效成分含量及品质的影响

以金银花为试材,对其进行叶面喷施亚硒酸钠,采用高效液相色谱法和紫外分光光度法,研究了外源硒对金银花叶片有效成分含量的影响,以期促进富硒金银花全草进一步综合利用,为金银花全草开发成食品或药品开拓更广阔的前景。结果表明:当亚硒酸钠浓度在10、20、50、100 mg·L^(-1)时对金银花的生长起到促进作用;当亚硒酸钠浓度为10 mg·L^(-1)时,绿原酸含量高达1.06%、可溶性糖含量高达1.51%、可溶性蛋白质含量为32.51 mg·g^(-1),较对照增加幅度分别为33.62%、57.29%、27.49%。当亚硒酸钠浓度为50 mg·L^(-1)时,异绿原酸A、异绿原酸C、维生素C含量达到峰值分别为1.36%、0.95%、0.73 mg·g^(-1),此时浓度较对照分别增加了20.80%、4.58%、58.69%。当亚硒酸钠浓度为100 mg·L^(-1)时,木犀草苷最大值为1.66%,与对照提高了40.19%。综上所述,适宜浓度的亚硒酸钠,对金银花的生长起到一定的促进作用,有助于金银花叶片中有效成分的合成与积累,从而提高金银花药食两用的品质。

亚硒酸钠对肺癌细胞迁移和血管生成的影响及其机制探究

目的:探讨亚硒酸钠(SS)对人非小细胞肺癌H520和A549细胞活力、迁移和血管形成模式的影响,并初步阐明其作用机制。方法:体外培养H520细胞、A549细胞及人脐静脉内皮细胞(HUVEC),分为对照组(0μmol/L SS)、低剂量组(5μmol/L SS)、中剂量组(10μmol/L SS)和高剂量组(20μmol/L SS)。采用CCK-8法检测各组细胞活力,计算半抑制浓度(IC_(50));细胞划痕实验检测各组细胞划痕愈合率;Transwell小室实验检测各组细胞迁移能力;血管形成实验检测亚硒酸钠对HUVEC血管管腔、肺癌细胞血管生成拟态管腔及肺癌细胞和HUVEC共同形成的“马赛克”血管管腔的影响;化学发光法检测各组肺癌细胞上清血管内皮生长因子(VEGF)表达量;RT-qPCR法检测VEGF、血管内皮生长因子受体2(VEGFR2)及血管紧张素Ⅱ(Ang Ⅱ)的mRNA表达水平;Western blot法检测H520和A549细胞中VEGF、p-PI3K和p-Akt蛋白水平。结果:SS处理48 h对HUVEC、A549细胞和H520细胞的IC_(50)值分别为6.762、9.003和7.356μmol/L。与各自对照组相比,SS处理48 h各组细胞划痕愈合率均降低(P<0.01);HUVEC中,中、高剂量组迁移细胞数减少(P<0.01);肺癌细胞系中,SS处理后各组迁移细胞数均减少(P<0.01);高剂量SS组VEGF、VEGFR2和Ang Ⅱ的mRNA水平表达量均降低(P<0.05,P<0.01);在H520细胞中,SS处理组VEGF、p-PI3K和p-Akt蛋白水平均降低(P<0.05,P<0.01)。结论:亚硒酸钠可抑制HUVEC、H520细胞及A549细胞活力及迁移,抑制肺癌细胞血管生成拟态及马赛克血管的形成,其机制可能与抑制PI3K-Akt信号通路激活及调控VEGF有关。

亚硒酸钠通过活性氧(ROS)/谷胱甘肽(GSH)/谷胱甘肽过氧化物酶4(GPX4)轴诱导非小细胞肺癌A549细胞铁死亡

硒作为人体必需的微量元素,具有抗癌作用,但其抗癌机制尚不明确,因此,通过探讨亚硒酸钠是否可以通过铁死亡途径抑制肺癌A549细胞增殖及其肺癌A549细胞发生铁死亡的具体机制。通过细胞增殖实验(CCK-8实验)及细胞计数实验评价亚硒酸钠对A549细胞增殖的影响,通过流式细胞术分析亚硒酸钠对肺癌A549细胞内线粒体膜电位(MMP)及活性氧(ROS)水平的影响,通过亚铁离子检测试剂盒检测亚硒酸钠作用后肺癌A549细胞内亚铁离子含量变化,MDA检测试剂盒分析亚硒酸钠作用后肺癌A549细胞内脂质氧化产物丙二醛(MDA)含量,分光光度法分析亚硒酸钠对肺癌A549细胞内谷胱甘肽过氧化物酶4(GPX4)及谷胱甘肽(GSH)的表达影响。研究发现:亚硒酸钠能够显著抑制肺癌A549细胞增殖,且亚硒酸钠抑制肺癌A549细胞的半数抑制率(IC_(50))为10μmol/L;亚硒酸钠能诱导肺癌A549细胞内ROS过度积累并使细胞内谷胱甘肽耗竭;亚硒酸钠作用后,细胞内线粒体膜电位水平显著降低,MDA含量升高而GPX4蛋白表达下调。研究表明,亚硒酸钠能通过诱导肺癌A549细胞内ROS过度积累,引起细胞内GSH大量耗竭,导致GPX4表达下降,诱导细胞发生铁死亡。

罗伊氏乳杆菌富集有机硒转化条件的研究

为筛选富有机硒罗伊氏乳杆菌添加剂的最优生产条件,试验以罗伊氏乳杆菌为研究对象,对其富集有机硒的理想条件进行探索。将不同质量浓度的无菌亚硒酸钠(0、20、40、60、80、100、120μg/mL)加入到改良的乳酸菌培养基(MRS培养基)中,进行耐硒试验,并观察菌落数(CFU)及菌落颜色,判定不同质量浓度的亚硒酸钠对罗伊氏乳杆菌生长的影响;采用3,3’-二氨基联苯胺(3,3’-DAB)分光光度法测定罗伊氏乳杆菌富集有机硒的含量。结果表明,每克菌体转化的硒量不同亚硒酸钠浓度组之间差异极显著(P <0.01),当亚硒酸钠浓度在100μg/mL时,罗伊氏乳杆菌有机硒的转化量为4.40 mg/g,转化率为13.3%,达到有机硒富集的最大临界值,且此浓度对罗伊氏乳杆菌增殖影响较小。

嗜酸乳杆菌(Lactobacillus acidophilus)合成纳米硒特性研究

乳酸菌具有还原亚硒酸钠为纳米硒的能力。为了采用更加环境友好的方式获得纳米硒颗粒,本研究首先探索了培养基中加硒浓度、加硒时间,以及培养时长对嗜酸乳杆菌(Lactobacillus acidophilus)合成纳米硒的影响,随后对所产的纳米硒颗粒的粒径、zeta电位及抑菌活性进行研究。结果表明,当培养基中硒含量为0~600μg/mL时,硒浓度越高,转化得到的纳米硒越多;当培养基中硒浓度高于600μg/mL时,发酵液中的纳米硒含量反而减少。在嗜酸乳杆菌生长的对数中前期,即第6 h时添加亚硒酸钠,更有利于纳米硒的合成。而培养至32 h后,纳米硒几乎不再继续合成。通过扫描电镜及粒径和电位仪分析发现,嗜酸乳杆菌所产的纳米硒颗粒呈球形,且超声破碎有助于其释放;纳米硒颗粒带负电荷,电位绝对值为40~50 mV,粒径大小较多分布于170~210 nm,具有良好的稳定性。抑菌实验结果表明,嗜酸乳杆菌还原亚硒酸钠所产的纳米硒对大肠杆菌、沙门氏菌、金黄色葡萄球菌和枯草芽孢杆菌的生长均具有抑制作用。综上,嗜酸乳杆菌可以将亚硒酸钠还原合成纳米硒,且所产的纳米硒颗粒具有良好的抑菌活性。

7.0 T MRI评估青藏高原环境下亚硒酸钠改善大鼠肺动脉高压后左心室功能的初步研究

目的利用心脏磁共振(cardiac magnetic resonance,CMR)组织追踪技术评估高原低氧环境下亚硒酸钠(sodium selenite,SE)对肺动脉高压(pulmonary arterial hypertension,PAH)后左心室功能的改善作用并初步探索SE提升PAH后左心室功能的潜在机制。材料与方法46只雄性SD大鼠于购置第二日从成都(海拔500 m)陆运至青海省玉树藏族自治州高原动物实验室(海拔4250 m),随机分为对照组(n=10)、模型组[野百合碱(monocrotaline,MCT)组,n=20]和治疗组(SE组,n=16)。高原低氧环境下饲养28周后,MCT组和SE组大鼠均接受一次性腹腔注射60 mg/kg的MCT以建立PAH模型,而对照组则接受等量的生理盐水注射。一周后,SE组大鼠通过灌胃方式给予0.7 mg/kg的SE持续治疗一个月,对照组和MCT组进行常规饲养。干预完成后将大鼠运回成都。随机从三组中各选取8只大鼠进行CMR成像,以评估左心室功能、应变和T2弛豫时间。CMR扫描结束后取材大鼠心脏组织和血液分别进行病理、血生化检测。结果相较于对照组,MCT组的左心室射血分数(left ventricular ejection fraction,LVEF)(61.36%±4.50%)和左心室整体周向应变(left ventricular global circumferential strain,LVGCS)(−19.81%±0.84%)显著降低(P值均<0.05)。然而,与MCT组相比,SE组的LVEF(75.29%±5.67%)、左心室整体径向应变(left ventricular global radial strain,LVGRS)(42.90%±5.94%)和LVGCS(−21.43%±1.33%)明显提高(P值均<0.05),表明SE治疗提高了PAH后左心室功能。对照组和MCT组血清中谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的含量差异具有统计学意义[对照组vs.MCT组:(16544.38±3734.02)U/mL vs.(9974.00±900.80)U/mL,P<0.05],MCT组血清中丙二醛(malondialdehyde,MDA)相较于对照组有所增加[MCT组vs.对照组:9.00(7.60,13.20)μmol/L vs.3.86(3.60,6.20)μmol/L,P<0.01],提示MCT组大鼠抗氧化能力下降。经SE干预后,SE组的大鼠表现出血清中超氧化物歧化酶(superoxide dismutase,SOD)(292.60±44.38)U/mL和GSH-Px(17843.26±3585.44)U/mL水平的升高以及MDA[5.37(5.10,6.20)μmol/L]水平的降低(P值均<0.05)。凋亡染色表明,与对照组相比,MCT组左心室的相对荧光强度显著增高(P<0.001),而治疗后SE组的相对荧光强度较MCT组明显降低(P<0.001)。结论CMR组织追踪技术能够定量评估肺动脉高压后左心室功能的异常;SE在高原低氧环境下能改善PAH后左心室功能,其机制可能与其提高大鼠抗氧化能力、减轻心肌细胞凋亡有关。

蚯蚓处理添加不同硒源牛粪的比较研究

根据蚯蚓的生长繁殖和蚓体富硒情况,选出两种不同的硒源按不同的浓度混入牛粪中,利用蚯蚓处理牛粪,实现养殖业粪污的资源化利用。试验利用亚硒酸钠(Sodium selenite,SS)与富硒酵母(Selenium enriched yeast,SY)易富硒、价格低廉优势,选取亚硒酸钠和富硒酵母作为硒源添加剂,促进蚯蚓对硒富集,生产优质富硒肥料。探索有机硒与无机硒对蚯蚓生长繁殖的影响,以期实现蚯蚓养殖处理粪污的同时生产富硒肥料,提高特种养殖经济效益。试验通过在牛粪基料中添加2种硒源(亚硒酸钠SS、富硒酵母SY)、3个水平(5、10、15 mg·kg^(-1)),以硒元素计,选择出两种硒源的最适富硒量。结果表明,随着牛粪中硒添加量升高,蚯蚓的生长繁殖逐渐被抑制,硒浓度越高,蚯蚓的生长繁殖被抑制程度越高,当SY的硒添加量为15 mg·kg^(-1)时,蚯蚓有明显的中毒现象;硒浓度越高,蚯蚓体硒含量越高,二者成正比;牛粪中添加同一水平的SS与SY,SY组蚯蚓的硒含量明显高于SS组。

枸杞多糖和亚硒酸钠对镉致大鼠肝毒性的拮抗作用研究

目的:探究枸杞多糖(LBP)和亚硒酸钠(Na_(2)SeO_(3))对镉(Cd)致大鼠肝毒性的拮抗作用。方法:40只SD大鼠随机分为对照组、CdCl_(2)组、LBP组、Na_(2)SeO_(3)组、LBP联合Na_(2)SeO_(3)组,每组8只。对照组不造模,其余四组腹腔注射CdCl_(2)染毒。染毒1 h后,对照组和CdCl_(2)组给予生理盐水灌胃,LBP组、Na_(2)SeO_(3)组分别给予LBP、Na_(2)SeO_(3)灌胃,LBP联合Na_(2)SeO_(3)组给予LBP和Na_(2)SeO_(3)灌胃,每日染毒和灌胃各进行1次,共干预35 d。观察各组大鼠肝脏病理改变,测定大鼠肝组织Cd含量;检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、直接胆红素(DB)及总胆红素(TB)的含量以及肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)含量;Western blot检测肝组织中苹果酸脱氢酶(MDH)、琥珀酸脱氢酶(SDH)、铁调节蛋白(IRP-1)和谷胱甘肽过氧化物酶4(GPX4)的蛋白表达水平。结果:与CdCl_(2)组、LBP组和Na_(2)SeO_(3)组相比,LBP联合Na_(2)SeO_(3)组肝细胞排列更紧密,细胞核更清晰可见,肝小叶中央静脉无淤血。相比CdCl_(2)组,LBP联合Na_(2)SeO_(3)组能降低Cd在大鼠肝脏的蓄积(P<0.05)。LBP联合Na_(2)SeO_(3)组与CdCl_(2)组相比,血清ALT、AST水平降低(P<0.05);LBP联合Na_(2)SeO_(3)组与CdCl_(2)组相比,大鼠肝脏组织中SOD、GSH-Px水平显著升高,MDA降低(P<0.05);LBP联合Na_(2)SeO_(3)组大鼠肝脏组织中MDH、SDH、IRP-1、GPX4的蛋白表达水平较CdCl_(2)组、LBP组和Na_(2)SeO_(3)组升高(P<0.05)。结论:LBP和Na_(2)SeO_(3)联合干预可能通过增强大鼠肝脏的抗氧化能力拮抗Cd诱导的肝损伤。

亚硒酸钠通过增加ROS抑制PI3K/AKT通路改善肺癌PC-9/GR细胞对吉非替尼的耐药性

目的:探讨亚硒酸钠对肺癌耐药细胞PC-9/GR增殖、凋亡的影响,研究其是否能改善吉非替尼耐药及可能机制。方法:不同浓度(0、5、10、20、40μmol/L)亚硒酸钠处理细胞24、36、48 h后,CCK-8法检测亚硒酸钠对细胞增殖的影响并选择合适浓度用于后续实验。不同浓度(0、2.5、5、10、20、40μmol/L)吉非替尼单药及联合亚硒酸钠(6μmol/L)处理细胞48 h,分别计算半数抑制浓度(IC50),得出亚硒酸钠对PC-9/GR逆转倍数;流式细胞术检测各组细胞凋亡;DCFH-DA法检测细胞内ROS水平;Western blot实验检测各组细胞中p-PI3K、p-AKT、Bax、Bcl-2表达水平。结果:随亚硒酸钠浓度升高及作用时间延长,细胞增殖抑制率逐渐升高(P<0.05);单药吉非替尼组的IC50值为16.051μmol/L,联合亚硒酸钠后IC50值为5.406μmol/L,表明亚硒酸钠能够逆转吉非替尼的耐药,其逆转耐药倍数为2.969倍。与吉非替尼和亚硒酸钠单药组相比,联合治疗组的细胞凋亡率显著升高,ROS水平及Bax蛋白表达上调,p-PI3K、p-AKT、Bcl-2表达下调,经N-乙酰半胱氨酸(NAC)消除ROS后抵消了亚硒酸钠对PI3K/AKT通路的抑制作用(P<0.05)。结论:亚硒酸钠联合吉非替尼能提高肺腺癌耐药细胞的敏感性,抑制细胞的增殖,同时诱导细胞凋亡,这一过程可能通过ROS依赖性下调PI3K/AKT通路的表达实现。

Mechanistic research:Selenium regulates virulence factors,reducing adhesion ability and inflammatory damage of Helicobacter pylori

BACKGROUND The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host.Although selenium is closely related to pathogenicity as an environmental factor,the specific correlation between them remains unclear.AIM To investigate how selenium acts on virulence factors and reduces their toxicity.METHODS H.pylori strains were induced by sodium selenite.The expression of cytotoxin-associated protein A(CagA)and vacuolating cytotoxin gene A(VacA)was determined by quantitative PCR and Western blotting.Transcriptomics was used to analyze CagA,CagM,CagE,Cag1,Cag3,and CagT.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction,and H.pylori colonization,inflammatory reactions,and the cell adhesion ability of H.pylori were assessed.RESULTS CagA and VacA expression was upregulated at first and then downregulated in the H.pylori strains after sodium selenite treatment.Their expression was significantly and steadily downregulated after the 5th cycle(10 d).Transcriptome analysis revealed that sodium selenite altered the levels affect H.pylori virulence factors such as CagA,CagM,CagE,Cag1,Cag3,and CagT.Of these factors,CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite.Moreover,CagT expression was upregulated before the 3rd cycle(6 d)and significantly downregulated after the 5th cycle.Cag1 and Cag3 expression was upregulated and downregulated,respectively,but no significant change was observed by the 5th cycle.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction.The extent of H.pylori colonization in the stomach increased;however,sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H.pylori-infected mice,and the cell adhesion ability of H.pylori was significantly weakened.CONCLUSION These results demonstrate that H.pylori displayed virulence attenuation after the 10th d of sodium selenite treatment.Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H.pylori,thus mitigating the inflammatory damage to the gastric mucosa.