硒对自身免疫性甲状腺炎大鼠Nrf2表达和甲状腺细胞凋亡的影响

目的探讨硒对自身免疫性甲状腺炎(autoimmune thyroiditis,AT)大鼠Nrf2表达的影响及凋亡机制。方法通过甲状腺球蛋白免疫诱导AT大鼠模型,同时给予亚硒酸钠灌胃治疗。TUNEL染色检测甲状腺细胞凋亡情况,免疫荧光染色检测甲状腺Nrf2的表达,Western blot检测Nrf2、Bcl-2、Bax蛋白表达,同时检测各组大鼠自身抗体TGAb、TMAb水平及组织匀浆中SOD活性、MDA含量。结果 AT大鼠经过硒处理后Nrf2、Bcl-2表达及SOD活性明显增加,而Bax表达、MDA含量、TGAb、TMAb水平明显降低(均为P<0.05)。结论通过补硒可显著激活AT大鼠甲状腺Nrf2的表达,降低氧化应激水平,抑制甲状腺细胞凋亡,提示Nrf2可能通过对抗氧化应激损伤进而保护AT大鼠受损的甲状腺细胞。     

Effects of that ATRA inhibits Nrf2-ARE pathway on glial cells activation after intracerebral hemorrhage

Previous studies indicate that the Nrf2-ARE signaling pathway plays a neruo-protective role in glia cell, however, the mechanism was also elusive. This study aims to explore the inhibitive function of all-trans-retinoic (ATRA) on Nrf2-ARE pathway in intracerebral hemorrhage (ICH), and investigate the mechanism. In this study, the femoral artery injection method was employed to establish ICH model. The model rats were randomly divided into four groups, including Sham group, ICH group, ATRA group and DMSO group. The neurological scores were evaluated for the four groups at different time points. Hematoxylin-Eosin staining was used to stain the CD11b positive glia cells. Double immunofluorescence staining method was utilized to observe the co-expression of HO-1, NF-κB, Nrf2 and TNF-α and CD11b marker in glia cells. Western blot assay was used to detect the Nrf2 protein (total and binding Nrf2), HO-1, NF-κB and TNF-α proteins in every group. The results indicated that neurologiclal scores were significantly decreased in ATRA group compared to ICH gorup (P < 0.05). The glia cells were significantly activated and accumulated in ICH rats. ATRA significantly decreased co-expression of Nrf2, HO-1 and CD11b, and increased co-expression of NF-κB, TNF-α and CD11b of glia cells. ATRA significantly decreased total Nrf2 expression and increased binding Nrf2 expression in ATRA group compared to ICH group (P < 0.05). ATRA decreased anti-oxygen protein Nrf2 and HO-1, and increases inflammatory factors NF-κB and TNF-α. In conclusion, the application of ATRA could inhibit the neuro-protective function effectively by blocking the Nrf2-ARE pathway in glia cells.     

连翘苷元对老年大鼠氧化应激和肾功能的改善作用

目的　研究连翘苷元对老年大鼠氧化应激和肾功能的影响及相关机制。 方法　将15只 SD雌性老年大鼠（24月龄）随机分成3组,每组5只,老年对照组（Aged rats）,老年连翘苷元低剂量组[Aged rats+FA(20 mg/kg)],老年连翘高剂量组[Aged rats+FA(100 mg/kg)]。另取5只12周龄SD雌性大鼠为青年对照组（Young rats）。连翘苷元低、高剂量组大鼠灌胃给药60 d。考马斯亮蓝检测24 h尿液总蛋白并分析血清肌酐和尿素氮水平。HE染色和TUNEL染色检测肾组织病理损伤情况。Western Blot检测Caspase-3和Caspase-9的表达。检测氧化应激标记物超氧化物歧化酶（SOD）、丙二醛（MDA）和还原型谷胱甘肽（GSH）的水平。ELISA检测血清中炎症因子IL-18和IL-1β水平。Western Blot检测核因子E2相关因子（Nrf 2）、血红素氧合酶1（HO-1）和还原型辅酶/醌氧化还原酶（NQO-1）的表达。 结果　老年对照组与青年对照组相比,尿中蛋白含量显著提升,血清中肌酐和尿素氮含量显著上升;肾组织细胞排列不规则,出现大量炎性细胞浸润,凋亡细胞比率显著提高;Caspase-3和Caspase-9的表达水平显著上调;SOD活性显著降低,MDA含量显著上升,GSH含量显著下降;血清中IL-18和IL-1β含量显著升高;Nrf 2、HO-1和NQO-1的表达显著下调。连翘苷元低、高剂量组与老年对照组相比,尿液中蛋白含量显著降低,血清肌酐和尿素氮含量显著下降;肾组织细胞排列趋向规则,炎性细胞浸润明显减弱,凋亡细胞比率显著下降;Caspase-3和Caspase-9的表达水平显著下调;SOD活性显著提高,MDA含量显著降低,GSH含量显著上升;血清中IL-18和IL-1β含量显著降低;Nrf 2、HO-1和NQO-1的表达显著上调。 结论　连翘苷元抑制老年大鼠氧化应激反应,改善老年大鼠肾功能,其作用机制可能与Nrf 2-ARE通路激活相关。     

Targeted polymeric therapeutic nanoparticles: Design and interactions with hepatocellular carcinoma

Nanoparticles (NPs) have great potential as drug delivery systems or as drugs for treating certain diseases. We designed three NPs with different charges and modifications with PEG to treat tumors. PDLA-CS, PEG-PLGA-PLL, and PEG-PS/CaP NPs were designed and evaluated to assess NPs fate in vivo and efficacy for treating tumors. Comparison between PEG-modified and non-PEG-modified NPs showed that PEG-modified NPs increased K⁺ efflux, easily escaped from lysosomes, affected the mitochondria, induced mitochondrial apoptosis, had longer circulation time, and easily targeted tumors. Non-PEG-modified NPs induce the endoplasmic reticulum apoptosis pathway. Comparison between positively and negatively charged NPs showed that negatively charged NPs have less effect on the K⁺ efflux of normal cells and more effect on the mitochondrial apoptosis of tumor cells. Positively charged NPs accumulated within the tumors and the liver and lungs. These results provide a theoretical basis for future clinical applications.     

氢分子对高糖状态下肾小球系膜细胞凋亡相关蛋白及Nrf2信号通路的影响

目的:探讨氢分子对高糖状态下肾小球系膜细胞凋亡相关蛋白Bax、Bcl-2和cleaved caspase-3表达水平的影响及其可能的机制。方法:体外培养小鼠肾小球系膜细胞,实验分为正常对照组(C组,5.5 mmol/L葡萄糖)、甘露醇组(G组,5.5 mmol/L葡萄糖+19.5 mmol/L甘露醇)、高糖组(H组,25 mmol/L葡萄糖)和高糖+富氢水组(HH组,25 mmol/L葡萄糖+富氢水),培养48 h。采用Western blot法检测Bax、Bcl-2、cleaved caspase-3、核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)和NAD(P)H:醌氧化还原酶1(NQO-1)的蛋白水平;RT-PCR检测HO-1和NQO-1的mRNA表达;超氧化物阴离子荧光探针二氢乙啶检测活性氧簇(ROS)的水平;总超氧化物歧化酶(SOD)活性检测试剂盒(WST-8法)检测SOD活性。结果:与C组比较,H组Bax和cleaved caspase-3的蛋白水平增加,Bcl-2蛋白表达减少(P0.05),而HH组上述蛋白表达水平与C组的差异均无统计学显著性;与H组比较,HH组的Bax和cleaved caspase-3蛋白下调,Bcl-2蛋白上调(P0.05)。H组细胞内的ROS水平较C组明显增高,SOD活性较C组明显降低(P0.05),而HH组的SOD活性与C组比较差异无统计学显著性;HH组细胞内的ROS水平较H组明显降低,SOD活性明显高于H组(P0.05)。与C组比较,H组的Nrf2蛋白以及HO-1和NQO-1 mRNA及蛋白表达均减少(P0.05);HH组的Nrf2、HO-1和NQO-1蛋白以及HO-1和NQO-1的mRNA表达均明显高于H组(P0.05)。结论:氢分子可抑制高糖状态下肾小球系膜细胞促凋亡蛋白的表达,同时诱导其抗凋亡蛋白的表达,其机制可能与激活Nrf2信号通路有关。     

紫草素对高糖诱导的血管内皮细胞凋亡和氧化应激的影响

目的:探讨紫草素(shikonin)对高浓度葡萄糖诱导的血管内皮细胞凋亡和氧化应激水平的影响及其可能的作用机制。方法:体外培养的大鼠胸主动脉内皮细胞随机分为5组:正常对照组(培养基中葡萄糖浓度为5.5 mmol/L)、高糖组(培养基中葡萄糖浓度为33 mmol/L)、高糖+低浓度紫草素组(培养基中葡萄糖浓度为33mmol/L,紫草素浓度为0.1μmol/L)、高糖+中浓度紫草素组(培养基中葡萄糖浓度为33 mmol/L,紫草素浓度为1μmol/L)和高糖+高浓度紫草素组(培养基中葡萄糖浓度为33 mmol/L,紫草素浓度为10μmol/L)。各组细胞经相应处理后,CCK-8法检测细胞活力,流式细胞术检测细胞的凋亡率;此外,检测细胞中丙二醛(malondialdehyde,MDA)、活性氧簇(reactive oxygen species,ROS)、超氧化物歧化酶(superoxide dismutase,SOD)及谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的水平,以反映细胞的氧化应激状态;Western blot检测Nrf2/HO-1信号通路的活性。结果:相较于高糖组,紫草素处理可呈剂量依赖性地逆转高糖所致的内皮细胞活力降低及凋亡率增加。与正常对照组相比,高浓度葡萄糖可升高内皮细胞中MDA和ROS的含量,同时降低SOD和GSH-Px的活性;相较于高糖组,给予紫草素干预后,细胞内MDA和ROS的含量降低,SOD和GSH-Px的活性升高。此外,高糖可致内皮细胞中cleaved caspase-3、HO-1及核内Nrf2蛋白表达的增加;与高糖组相比,给予紫草素干预后细胞中cleaved caspase-3、HO-1和核内Nrf2的表达部分下降。结论:紫草素可显著改善高糖所致的血管内皮细胞凋亡,其作用机制可能与激活Nrf2/HO-1信号通路并降低细胞的氧化应激水平有关。     

低硒对大鼠血浆PGI2水平和血液流变性的影响

目的：研究低硒对微循环功能的影响。方法：采用低硒饲料饲养大鼠１４ 周,造成大鼠贫硒后,测定其血浆中前列腺环素（ＰＧＩ２） 和血栓烷Ａ２（ＴＸＡ２） 水平及部分血液流变学指标。结果： 低硒组血硒含量及谷胱甘肽过氧化物酶（ ＧＳＨ－ ＰＸ） 活性显著低于用常规饲料饲养的对照组,血浆６ － 酮－ ＰＧＦ１α浓度也显著低于对照组,但其血浆脂质过氧化物（ＬＰＯ） 水平显著高于对照组（ Ｐ＜ ０ ．０５） 。与此同时,低硒组与对照组在红细胞聚集指数、血沉方程Ｋ 值和红细胞变形能力等血液流变学指标上差异显著（ Ｐ＜ ０ ．０５） ,低硒组的红细胞聚集指数和血沉方程Ｋ 值分别为对照组的１１４ ．８ ％和１４９ ．０ ％ , 而红细胞变形能力仅为对照组的７３ ．８ ％ 。在低硒饲料中补硒可在一定程度上纠正这些变化。结论：硒不足可通过影响ＰＧＩ２ 的合成和红细胞特性而损害微循环功能。     

胰岛素联合硒协同抗糖尿病心肌细胞凋亡的作用

目的:观察胰岛素联合硒对糖尿病心肌病(diabetic cardiomyopathy,DCM)大鼠心肌细胞凋亡、Ku70、乙酰化Ku70、Bax和细胞色素C(cytochrome C)蛋白水平的影响,初步探讨胰岛素和硒协同抗DCM的机制。方法:将SD大鼠50只随机分为空白对照组(control组)、糖尿病心肌病模型组(DCM组)、糖尿病心肌病+胰岛素(DCM+In)组、糖尿病心肌病+硒(DCM+Se)组和糖尿病心肌病+胰岛素+硒(DCM+In+Se)组。流式细胞术检测心肌细胞线粒体膜电位;末端脱氧核糖核苷酸转移酶介导的缺口末端标记(terminal deoxynucleotidyl transferasemediated nick end labeling,TUNEL)法观察心肌细胞凋亡;Western blot法观察Ku70、Bax和cytochrome C蛋白水平的变化;免疫共沉淀法检测Ku70乙酰化。结果:与对照组比较,DCM组大鼠心肌细胞发生明显凋亡(P0.01),Ku70和乙酰化Ku70表达明显增加(P0.01),Bax由胞浆向线粒体转位同时cytochrome C由线粒体向胞浆转位(P0.01);与DCM+In组或DCM+Se组比较,胰岛素联合硒明显抑制心肌细胞凋亡(P0.05),下调Ku70以及乙酰化Ku70的表达(P0.05)并阻止Bax和cytochrome C转位(P0.05)。结论:胰岛素和硒可能通过调控Ku70乙酰化和抑制Bax转位而协同抗糖尿病心肌细胞凋亡。     

Inhibition of tumor growth and vasculature and fluorescence imaging using functionalized ruthenium-thiol protected selenium nanoparticles

Here we reported the high tumor targeting efficacy of luminescent Ru(II)-thiols protected selenium nanoparticles (Ru-MUA@Se). We have shown that a dual-target inhibitor Ru-MUA@Se directly suppress the tumor growth but also block blood-vessel growth. We also determined that the nanoparticles entered the cells via clathrin-mediated endocytosis pathway. In a xenograft HepG2 tumor model, we found that Ru-MUA@Se effectively inhibited tumor angiogenesis and suppressed tumor growth with low side effects using metronomic chemotherapy with Ru-MUA@Se. In vivo investigation of nanoparticles on nude mice bearing HepG2 cancer xenografts confirmed that Ru-MUA@Se nanoparticles possessed high tumor-targeted fluorescence imaging, exhibited enhanced antitumor efficacy and decreased systemic toxicity. Moreover, Ru-MUA@Se not only significantly induced dose-dependent disruption of mitochondrial membrane potential in HepG2 cells after 24 h treatment, but it also enhanced reactive oxygen species (ROS) generation. Our results suggest that the potential application of these Ru-MUA@Se nanoparticles in targeting cancer imaging and chemotherapy.     

Synthesis and characterization of PEG-coated poly(ethyl cyanoacrylate) nanoparticles

INTRODUCTION　　 Recently,as drug delivery,colloidal polymeric systems have gained a lot ofattention〔1〕. They were able to prevent drug degradation,control its release andachieve specific targeting.However polymeric nanoparticles were eliminated fromthe bloodstream by the macrophages of the mononuclear phagocyte system(MPS)within seconds orminites. Itisreported thatnanoparticlesattaching hydrophilicandflexible,such as poly(ethylene glycol) (PEG) can dramatically increase bloodcirculat…     

富血小板血浆联合髓芯减压调控激素性股骨头坏死模型兔氧化应激反应

背景:氧化应激在股骨头坏死损伤中发挥重要作用,富血小板血浆富含生长因子,可以加快骨折愈合,配合髓芯减压术能促进非创伤性股骨头坏死的恢复。目的:探讨富血小板血浆联合髓芯减压术能否通过Keap1/Nrf2/HO-1信号通路抑制兔激素性股骨头坏死模型氧化应激反应。方法:将40只实验新西兰兔随机分为正常组、模型组、对照组和富血小板血浆组,每组10只。除正常组外其他3组兔在无菌环境下建立激素性股骨头坏死模型,术后4周向富血小板血浆组动物股骨头内髓芯减压后注射植入0.4 mL 3%的富血小板血浆,对照组兔只进行髓芯减压术治疗,对照组与模型组兔正常饲养。14周后苏木精-伊红染色观察各组兔股骨头骨髓腔内病理学变化和骨陷窝空缺率,检测各组兔血清中总抗氧化能力、超氧化物歧化酶、谷胱甘肽过氧化物酶、还原型谷胱甘肽及丙二醛等氧化应激指标活性,TUNEL检测股骨头组织内骨细胞凋亡情况,免疫荧光检测股骨头组织内Keap1、Nrf2分布,Western Blot检测股骨头组织内Keap1、Nrf2、HO-1蛋白表达。实验方案经青海大学附属医院动物实验伦理委员会批准(批准号为qhdx-201908374)。结果与结论:①与正常组相比,模型组骨组织内骨小梁变细,结构紊乱;对照组较模型组有所改善,骨小梁结构得到恢复,空骨陷窝减少(P<0.05),富血小板血浆组经富血小板血浆联合髓芯减压治疗较对照组得到进一步改善,骨小梁结构更加完善,空骨陷窝进一步减少(P<0.05),与正常组无显著差异(P>0.05);②模型组血清中总抗氧化能力、超氧化物歧化酶、谷胱甘肽过氧化物酶和还原型谷胱甘肽的含量均显著低于正常组(P<0.05),而丙二醛浓度显著高于正常组(P<0.05);对照组以上指标稍有改善,但与模型组比较差异不显著(P>0.05);富血小板血浆以上氧化应激指标较模型组和对照组明显改善(P<0.05);③模型组股骨头组织内Keap1蛋白表达显著低于正常组(P<0.05),Nrf2、HO-1蛋白表达显著高于正常组(P<0.05);富血小板血浆组股骨头组织内Keap1的表达较模型组和对照组低(P<0.05),Nrf2、HO-1的表达显著高于模型组和对照组(P<0.05);④结果提示,富血小板血浆能有效抑制兔激素性股骨头坏死过程中氧化应激反应,该作用可能是通过激活Keap1/Nrf2/HO-1信号通路活性而发生的。     

One-step mixing with humanized anti-mPEG bispecific antibody enhances tumor accumulation and therapeutic efficacy of mPEGylated nanoparticles

Methoxy PEGylated nanoparticles (mPEG-NPs) are increasingly used for cancer imaging and therapy. Here we describe a general and simple approach to confer tumor tropism to any mPEG-NP. We demonstrate this approach with humanized bispecific antibodies (BsAbs) that can bind to both mPEG molecules on mPEG-NPs and to EGFR or HER2 molecules overexpressed on the surface of cancer cells. Simple mixing of BsAbs with mPEG-NPs can mediate preferential binding of diverse mPEG-NPs to cancer cells that overexpress EGFR or HER2 under physiological conditions and significantly increase cancer cell killing by liposomal doxorubicin to EGFR⁺ and HER2⁺ cancer cells. BsAbs modification also enhanced accumulation of fluorescence-labeled NPs and significantly increased the anticancer activity of drug-loaded NPs to antigen-positive human tumors in a mouse model. Anti-mPEG BsAbs offer a simple one-step method to confer tumor specificity to mPEG-NPs for enhanced tumor accumulation and improved therapeutic efficacy.     

Taurine induces upregulation of p53 and Beclin1 and has antitumor effect in human nasopharyngeal carcinoma cells in vitro and in vivo

Taurine is an amino acid that has several physiological functions. Previously, we reported the apoptosis-inducing effect of taurine in human nasopharyngeal carcinoma (NPC) cells in vitro. However, the effect of taurine on NPC cell growth in vivo has not been elucidated. Autophagy plays an important role in cell metabolism and exhibits antitumor effects under certain conditions. In this study, we investigated the effects of taurine on apoptosis- and autophagy-related molecules in NPC cells in vitro and in vivo. In our in vitro study, NPC cells (HK1-EBV) were treated with taurine, and Western blot and immunocytochemical analyses revealed that taurine co-upregulated Beclin 1 and p53, with autophagy upregulation. In the in vivo study, we used a nude mouse model with subcutaneous xenografts of HK1-EBV cells. Once the tumors reached 2–3 mm in diameter, the mice were provided with distilled water (control group) or taurine dissolved in distilled water (taurine-treated group) ad libitum (day 1) and sacrificed on day 13. The volume and weight of the tumors were significantly lower in the taurine-treated group. Using immunohistochemistry (IHC), we confirmed that taurine treatment reduced the distinct cancer nest areas. IHC analyses also revealed that taurine promoted apoptosis, as evidenced by an increase in cleaved caspase-3, accompanied by upregulation of p53. Additionally, taurine increased LC3B and Beclin 1 expression, which are typical autophagy markers. The present study demonstrated taurine-mediated tumor growth suppression. Therefore, taurine may be a novel preventive strategy for NPC.     

二甲双胍联合紫杉醇对人乳腺癌细胞凋亡及AMPK信号通路的影响

目的:探索二甲双胍联合紫杉醇对乳腺癌MCF-7细胞活力和凋亡的影响及其可能的机制。方法:采用不同浓度(2、5、10、20、40和80 mmol/L)二甲双胍作用于体外培养的MCF-7细胞,MTT法检测细胞的活力。采用2 mmol/L二甲双胍和2. 4 mg/L紫杉醇单独或联合处理细胞,并加入一磷酸腺苷活化的蛋白激酶(AMPK)信号转导通路抑制剂compound C。实验分为对照组、二甲双胍组、紫杉醇组、联合组和联合+compound C组;流式细胞术检测细胞的凋亡率,采用RT-qPCR和Western blot法检测Bax、Bcl-2和caspase-3的mRNA和蛋白表达量,Western blot检测AMPK和P21蛋白的表达量。结果:不同浓度二甲双胍(2、5、10、20、40和80 mmol/L)显著抑制乳腺癌细胞的活力(P 0. 05),且具有一定浓度依赖性。与对照组相比,2 mmol/L二甲双胍和2. 4 mg/L紫杉醇单独或联合均可显著抑制细胞活力并诱导其凋亡(P 0. 05),显著下调Bcl-2水平(P 0. 05),上调Bax和caspase-3水平(P 0. 05),促进AMPK和P21蛋白表达。联合使用的效果优于单独使用。加入AMPK抑制剂可削弱此作用。结论:二甲双胍联合紫杉醇可抑制乳腺癌MCF-7细胞活力,诱导其凋亡。此作用与激活AMPK信号转导通路并调节细胞凋亡信号通路有关。     

Cytotoxicity,oxidative stress,apoptosis and the autophagic effects of silver nanoparticles in mouse embryonic fibroblasts

With the advancement of nanotechnology, nanomaterials have been comprehensively applied in our modern society. However, the hazardous impacts of nanoscale particles on organisms have not yet been thoroughly clarified. Currently, there exist numerous approaches to perform toxicity tests, but common and reasonable bio-indicators for toxicity evaluations are lacking. In this study, we investigated the effects of silver nanoparticles (AgNPs) on NIH 3T3 cells to explore the potential application of these nanoparticles in consumer products. Our results demonstrated that AgNPs were taken up by NIH 3T3 cells and localized within the intracellular endosomal compartments. Exposure to AgNPs is a potential source of oxidative stress, which leads to the induction of reactive oxygen species (ROS), the up-regulation of Heme oxygenase 1 (HO-1) expression, apoptosis and autophagy. Interestingly, AgNPs induced morphological and biochemical markers of autophagy in NIH 3T3 cells and induced autophagosome formation, as evidenced by transmission electron microscopic analysis, the formation of microtubule-associated protein-1 light chain-3 (LC3) puncta and the expression of LC3-II protein. Thus, autophagy activation may be a key player in the cellular response against nano-toxicity.     

The combined effects of size and surface chemistry on the accumulation of boronic acid-rich protein nanoparticles in tumors

The high drug concentration and long-acting time within tumor tissues are a key challenge in cancer treatment. Here we prepare the boronic acid-rich bovine serum albumin nanoparticles with the size of 70 nm, 110 nm and 150 nm, and subsequently decorate particle surface with polyethyleneimine–polyethylene glycol copolymer and cRGD peptide. We demonstrated that the drug accumulation and particle residence time at tumor site can be significantly improved by incorporating boronic acid group into the bovine serum albumin nanoparticles, optimizing particle size and decorating particle surface. We show that the size- and surface chemistry-driven dual-actions lead to the doxorubicin accumulation at tumor site go beyond 12% injected dose per gram of tumor through such delivery system, which is 16-fold higher than that of free doxorubicin injected. Based on the systemic, tissue and cell level analysis, we demonstrated that the incorporated boronic acid group into the nanoparticles enhances the recognition ability of nanoparticles to cancer cells, and prolongs the action time of nanoparticles at tumor sites since the boronic acid group can reversibly and rapidly react with sialic acid residues which are overexpressed in cancer cells. These features make that this drug delivery system not only has significantly superior ability in impeding tumor growth, but also induces distinct shrinkage and apoptosis of tumor.     

Anti-inflammatory and anti-oxidant effects of combination between sulforaphane and acetaminophen in LPS-stimulated RAW 264.7 macrophage cells

Objectives: Accumulating evidence indicates that combination of therapeutic agents may increase their pharmacological properties with fewer undesired side effects. Acetaminophen (APAP) has been widely used to treat pain and fever in many countries. However, APAP only possesses a weak anti-inflammatory property at therapeutic dose, and exhibits hepatotoxicity at high dose. On other hand, sulforaphane (SFN) has been well-known as a potential anti-inflammatory and antioxidant agent. In this study, we investigated the anti-inflammatory and antioxidant effects of combination between APAP and SFN in LPS-stimulated RAW 264.7 macrophage cells.

Methods: Nitric oxide (NO) assay was determined using the Griess assay. Reactive oxygen species (ROS) formation was measured using an ROS-sensitive fluorescence indicator, DCFH-DA. The protein expression was determined by western blot analysis.

Results: Our results showed that the combination of SFN and APAP exhibited an inhibitory effect on inflammatory markers such as NO, iNOS, COX-2, and IL-1β, and this effect was more pronounced than the compound was used alone. In addition, the combination of SFN and APAP at low doses decreased intracellular ROS formation and increased the protein levels of CAT, GPx, Nrf2, NQO1, and HO-1, which were much better than APAP alone and were equivalent to SFN at full dose.

Conclusions: Our findings suggest that the combination of APAP and SFN enhanced anti-inflammatory and anti-oxidant activities in stimulated macrophages, which provide an important rationale to utilize drug and food in combination for prevention and/or treatment inflammation-related diseases.     

In vitro uptake and release of natamycin Dex-b-PLA nanoparticles from model contact lens materials

Purpose: To evaluate the uptake and release of the antifungal agent natamycin encapsulated within poly(D,L-lactide)-dextran nanoparticles (Dex-b-PLA NPs) from model contact lens (CL) materials. Methods: Six model CL materials (gel 1:poly(hydroxyethyl methacrylate, pHEMA); gel 2:85% pHEMA: 15% [Tris(trimethylsiloxy)silyl]-propyl methacrylate (TRIS); gel 3: 75% pHEMA: 25% TRIS; gel 4: 85% N,N dimethylacrylamide (DMAA): 15% TRIS; gel 5:75% DMAA: 25% TRIS; and gel 6: DMAA) were prepared using a photoinitiation procedure. The gels were incubated in: (1) natamycin dissolved in deionized (DI) water and (2) natamycin encapsulated within Dex-b-PLA NPs in dimethylsulfoxide/DI water. Natamycin release from these materials was monitored using UV–visible spectrophotometry at 304?nm over 7 d. Results: Natamycin uptake by all model CL materials increased between 1 and 7 d (p?p?p?p?Conclusions: Model CL materials loaded with natamycin-Dex-b-PLA NPs were able to release natamycin for up to 12?h under infinite sink conditions. DMAA-TRIS materials may be more suitable for drug delivery of natamycin due to the higher drug release observed with these materials.     

妊娠期糖尿病孕妇血清及新生儿脐血清和胎盘组织中硒含量研究

目的研究硒与妊娠期糖尿病的关系。方法分别测定正常孕妇、妊娠期糖尿病孕妇血清、新生儿血清、胎盘血清硒含量。结果正常孕妇组与妊娠期糖尿病组孕妇血清、新生儿血清、胎盘组织硒含量结果分别为:3.14±0.74mmol/L,2.08±0.56mmol/L,2.63±0.91mmol/L,1.89±0.81mmol/L,46.8±30.1mmol/L,35.8±12.6mmol/L。结论妊娠期糖尿的孕妇血清、新生儿血清及胎盘组织中硒的缺乏可能与妊娠期糖尿有关。     

归芪白术方联合奥沙利铂对胃癌荷瘤小鼠机体免疫炎症分子的影响及抑癌作用

目的:探讨归芪白术方联合奥沙利铂在IL-6/JAK2/STAT3通路中对MFC胃癌荷瘤小鼠的抑瘤作用及对炎症分子影响。方法:建立MFC胃癌荷瘤小鼠模型,随机分为模型组、奥沙利铂组、奥沙利铂加归芪白术方高、中、低剂量组,10只/组,另选10只健康小鼠作为空白组;各组小鼠经口灌胃给予相应药物,空白组、模型组给予生理盐水,连续治疗14 d。处死小鼠取脾脏、胸腺、肿瘤称重,计算脏器指数及抑瘤率;HE染色观察小鼠瘤体病理形态学变化;ELISA法检测小鼠血清中IL-6含量;RT-qPCR和Western blot分别检测瘤组织中IL-6、JAK2、STAT3 mRNA及IL-6、p-JAK2、p-STAT3蛋白含量;免疫组化法检测肿瘤组织中c-Myc、Cyclin D1蛋白。结果:各治疗组小鼠瘤体重量显著低于模型组(P<0.01),联合用药高、中剂量组瘤体重量明显低于奥沙利铂组(P<0.05,P<0.01);与空白组相比,模型组小鼠的脾指数、胸腺指数降低(P<0.01),与模型组相比,奥沙利铂组小鼠的脾指数、胸腺指数降低(P<0.01),与奥沙利铂组相比,联合用药高剂...