A Lanthanide-transition Metal Coordination Polymer:{[CuEu(Hbidc)_2(H_2O)_4]·H_2O}_n(H_3bidc=1H-benzimidazole-5,6-dicarboxylic Acid)

The title complex 1,{[CuEu（Hbidc）2（H2O）4]·H2O}n（H3bidc = 1H-benzimidazole-5,6-dicarboxylic acid）,has been solvothermally synthesized and structurally characterized by single-crystal X-ray diffraction.Complex 1 crystallizes in triclinic,space group P1,with a = 7.791（2）,b = 12.058（3）,c = 12.109（3）,α = 82.189（5）,β = 72.407（5）,γ = 89.184（4）°,V = 1073.7（5）3,C18H18CuEuN4O13,Mr = 713.86,Dc = 2.208 g/cm3,μ（MoKα） = 3.967 mm-1,F（000） = 700,GOOF = 0.950,Z = 2,the final R = 0.0531 and wR = 0.1068 for I 2σ（I）.Complex 1 possess a tape-like chain structure consisting of Eu2C8O4 and Cu2Eu2C18N4O4 metallic rings alternatively arranged and is the first 3d-4f heterometallic complex based on the 1H-ben-zimidazole-5,6-dicarboxylato ligand（Hbidc）.Plenty of hydrogen-bonding and π...π stacking interactions connect the 1D chains to construct a 3D supramolecular architecture.

Synthesis and fluorescence properties of Tb(Ⅲ) complexes with pyridine-2,6-dicarboxylic acid derivatives

Two novel ligands named 4-styrylpyridine-2,6-dicarboxylic acid (4-SPDA) and 4-(4-(2-(2, 6-dicarboxypyridin-4-yl)- vinyl)styryl)pyridine-2,6-dicarboxylic acid(DSPDA) and their complexes with Tb(Ⅲ) were synthesized and characterized by infrared spectrometry, 1H nuclear magnetic resonance, elemental analysis and gas chromatograph-mass spectrometry. The ligand synthetic route was optimized. The fluorescence properties of the complex in solid state, in different kind of solvents and in solutions with different pH values were investigated in detail. The results show that the yields of DSPDA and 4-SPDA reach over 78% by Wittig-Horner reaction and other eight pyridine-2, 6-dicarboxylic acid derivatives with different substituents on pyridine ring, and their complexes with Tb(Ⅲ) are also obtained. The fluorescence intensities of the complexes with electron-donating groups are more intense than those of the complexes with electron-withdrawing groups on pyridine ring; fluorescence intensities of the complexes are the strongest in neutral solution (pH=7), and the less the dipole moment of solvent molecule is, the stronger the fluorescence intensity is. It is found that the two ligands (4-APDA and DSPDA) are the good sensitizers for Tb(Ⅲ) ion.

Synthesis and Structural Characterization of a New Cadmium(Ⅱ) Complex Bridged by Endo-norbornene-cis-5,6-dicarboxylic Acid

A polynuclear complex [Cd（endc）（H20）]n·nH2O （endc = endo-norbornene-cis- 5,6-dicarboxylate anion） has been synthesized by the hydrothermal reaction of cadmium nitrate tetrahydrate with endo-norbornene-cis-5,6-dicarboxylic acid in 1：1 molar ratio, and structurally characterized by single-crystal X-ray diffraction. It crystallizes in monoclinic, space group P21/c with α = 1.16471（7）, b = 0.95334（7）, c = 0.91109（9） nm, Z= 4, V= 1.01035（14） nm^3, D, = 2.160 g/cm^3,μ = 2.172 mm^-1, F（000） = 648, R = 0.0302 and wR = 0.0752. According to structural analysis, each Cd（II） ion is coordinated to six O atoms from three endc anions and one water molecule, giving a distorted octahedral geometry. Two- dimensional layer arrangement of the title complex is constructed from the bridging nature of endc. It is worth notice that adjacent two-dimensional layers are joined together to form a three-dimensional supramolecular framework via intermolecular hydrogen bonding interactions.

Low-temperature heat capacities and standard molar enthalpy of formation of pyridine-2,6-dicarboxylic acid

This paper reports that the low-temperature heat capacities of pyridine-2,6-dicarboxylic acid were measured by a precision automatic calorimeter over a temperature range from 78 K to 380 K. A polynomial equation of heat capacities as a function of temperature was fitted by the least-squares method. Based on the fitted polynomial, the smoothed heat capacities and thermodynamic functions of the compound relative to the standard reference temperature 298.15 K were calculated and tabulated at intervals of 5 K. The constant-volume energy of combustion of the compound was determined by means of a precision rotating-bomb combustion calorimeter. The standard molar enthalpy of combustion of the compound was derived from the constant-volume energy of combustion. The standard molar enthalpy of formation of the compound was calculated from a combination of the datum of the standard molar enthalpy of combustion of the compound with other auxiliary thermodynamic quantities through a Hess thermochemical cycle.

The Synthesis of Pyridine 2,6-dicarboxylic Acid Using Microwave Irradiation

This research took 2,6-dimethylpyridine as raw materials under microwave irradiation to syntheses pyridine 2,6-dicarboxylic acid by adding oxidation potassium permanganate. However, there are lots of factors affecting the yield including the amount of potassium permanganate and sulfuric acid, reaction time, power, 2,6-dimethylpyridine dosage. We made the further research, using orthogonal experiment to find the optimal process conditions. Thus our research changed the synthesis process from a traditional method to a new type of microwave technology.

Synthesis of 3 or 4-Substituted Pyridine-2, 6-Dicarboxylic Acid

Various 4-alkoxypyridine-2, 6-dicarboxylic acids were synthesized starting from 2, 6- lutidine. Through aldol condensation and Michael addition, various 4-arylpyridine-2, 6-dicarboxylic acids were synthesized starting from aromatic aldehydes and 2-acetylfuran.

Syntheses, Crystal Structures, and Properties of Two New Lanthanide Coordination Polymers Constructed from Benzimidazole-5,6-dicarboxylic Acid

Two lanthanide coordination polymers, {[Ln（Hbidc）（bidc）（H2 O）3]·3 H2 O}n（H3 bidc = benzimidazole-5,6-dicarboxylic acid, Ln = Eu（1）, Sm（2）） have been hydrothermally synthesized. Both compounds are isostructure and crystallize in the P21/c space group of monoclinic system. Complex 1: a = 11.087（6）, b = 8.972（5）, c = 23.064（13） ?, b = 95.027（5）o, V = 2285.4（2） ?3, Z = 4, Mr = 669.35, Dc = 1.945 g/cm3, F（000） = 1328, S = 1.044, μ = 2.827 mm-1, R = 0.0393 and wR = 0.0801 for 3458 observed reflections（I > 2s（I））. Complex 2: a = 11.087（6）, b = 8.972（5）, c = 23.064（13） ?, b = 95.027（5）°, V = 2285.4（2） ?3, Z = 4, Mr = 667.74, Dc = 1.941 g/cm3, F（000） = 1324, S = 1.071, μ = 2.652 mm-1, R = 0.0329 and wR = 0.0809 for 3744 observed reflections（I > 2s（I））. Complexes 1 and 2 have been determined by single-crystal X-ray diffraction analyses and further characterized by elemental analyses, IR spectroscopy, and thermogravimetric analyses（TGA）. The single-crystal X-ray diffraction analysis reveals that complexes 1 and 2 are the isostructural 1 D zigzag chain structures, which are further extended into a 3 D supramolecular structure through hydrogen bonds and p···p stacking interactions. Furthermore, the thermal stability, UV-vis absorption spectra and fluorescent properties of complexes 1 and 2 have been investigated and discussed in detail.

Luminescence of Terbium Chelates with Substituted Pyridine-2, 6-Dicarboxylic Acid Derivatives by Synergistic Effect of EDTA

Some spectral properties and luminescence intensities of Tb 3+ chelates of substituted pyridine 2, 6 dicarboxylic acids and 4 phenyl pyridine 2, 6 dicarboxylic acid analogues were measured in some solutions (H 2O and EtOH etc.) by synergistic effect of EDTA. The substitution at the aromatic ring has a significant effect upon the observed luminescence intensities, excitation wavelengths, and lifetime of the complexes. Moreover, the changes in the environment cause great variation in those properties of certain Tb 3+ chelates. The results show that some of hte chelates (4 acetaminopoxypyridine 2, 6 dicarboxylic acid, 4 ethoxypyridine 2, 6 dicarboxylic acid and 4 methoxypyridine 2, 6 dicarboxylic acid etc.) have a stronger emission and longer lifetime at room temperature and may thus be used as perfectly sensitizers in fluorescence analysis.

Study on thermal decomposition kinetics of azobenzene-4,4′-dicarboxylic acid by using compensation parameter method and nonlinear fitting evaluation

Recently,azobenzene-4,4'-dicarboxylic acid(ADCA)has been produced gradually for use as an organic synthesis or pharmaceutical intermediate due to its eminent performance.With large quantities put into application in the future,the thermal stability of this substance during storage,transportation,and use will become quite important.Thus,in this work,the thermal decomposition behavior,thermal decomposition kinetics,and thermal hazard of ADCA were investigated.Experiments were conducted by using a SENSYS evo DSC device.A combination of differential iso-conversion method,compensation parameter method,and nonlinear fitting evaluation were also used to analyze thermal kinetics and mechanism of ADCA decomposition.The results show that when conversion rate α increases,the activation energies of ADCA's first and main decomposition peaks fall.The amount of heat released during decomposition varies between 182.46 and 231.16 J·g^(-1).The proposed kinetic equation is based on the Avrami-Erofeev model,which is consistent with the decomposition progress.Applying the Frank-Kamenetskii model,a calculated self-accelerating decomposition temperature of 287.0℃is obtained.

A 2D Metal-Organic Framework Based on 9-（Pyridin-4-yl）-9H- carbazole-3,6-dicarboxylic Acid： Synthesis, Structure and Properties

A metal-organic framework （MOF） formulated as [Cd2（μ3-L）2（DMF）4]·H2O （CdL） [H2L=9-（pyridin-4-yl）- 9H-carbazole-3,6-dicarboxylic acid, DMF=N,N-dimethylformamide] was synthesized under solvothermal condition. Crystal structural analysis reveals that CalL features the layered 2D framework with L2- ligands as 3-connected nodes. The compound CdL emits blue-violet light with the narrow emission peak and the emission maximum at 414 nm upon excitation at the maximum excitation wavelength of 340 nm. The compound CalL has a similar emission spectrum curve to the free H2L ligand that indicates the emission of compound CdL should be originated from the coordinated L2 ligands.

Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

Structure and Photoluminescence of a 3D Coordination Polymer from Triazole and 2,6-Dimethylpyridine-3,5-dicarboxylic Acid

A new metal-organic coordination polymer [Zn2（trz）2（mpda）（H2O）]n（1, trz = 1,2,4-triazole, H2 mpda = 2,6-dimethylpyridine-3,5-dicarboxylic acid） was synthesized and characterized by single-crystal X-ray analyses. The crystal is of monoclinic system, space group P21/n, a = 9.619（3）, b = 8.920（3）, c = 22.159（6）, β = 96.897（4）°, V = 1887.3（9）3, Z = 4, Mr = 478.04, D3 c = 1.682 Mg/m, F（000） = 960, the final R = 0.0264 and wR = 0.0870（I 2σ（I））. Compound 1 consists of {[Zn4（trz）4]4＋}n layers, which are further connected by mpda2- to complete a three-dimensional structure. The title compound exhibits luminescence at λmax = 415 nm upon excitation at 364 nm.

A One-dimensional Cd(Ⅱ)Coordination Polymer Constructed from 1,4-Benzene-dicarboxylic Acid and 3-(2,6-Di(pyrazin-2-yl)pyridin-4-yl)-1H-indole:Synthesis,Structure and Photoluminescence

A new coordination polymer {[Cd（C_（21）H_（14）N_6）（C_8H_4O_4）]·H_2O}_n（1） was synthesized by an elaborate design via the reaction of 3-（2,6-di（pyrazin-2-yl）pyridin-4-yl）-1H-indole（bppi）,1,4-benzene-dicarboxylic acid（H2bdc） and cadmium（Ⅱ） nitrate in CH_3OH/H_2O mixed solvents. Complex 1 crystallizes in orthorhombic,space group Ccca with a = 20.012（4）,b = 31.881（6）,c = 19.808（4） ？,V = 12638（4） ？~3,Z = 16,C_（29）H_（20）CdN_6O_5,M_r = 644.91,D_c = 1.356 g·cm^（-3）,μ = 0.735 mm^（-1）,F（000） = 5184,GOOF = 1.046,the final R = 0.0405 and wR = 0.1063 for 6870 observed reflections（I 〉 2σ（I））. The Cd（Ⅱ） centre is hepta-coordinated by three N and four O atoms from one bppi terminal ligand and two bdc2– ligands,respectively,displaying a capped trigonal prism geometry. Structure extension gives coordination polymeric chains,in which the bdc2– linkers connect Cd（Ⅱ） cations into a one-dimensional（1D） coordination polymer along the c axis,giving zigzag chains with the Cd···Cd separation of 11.178（1） ？. The adjacent bppi terminal ligands in the chains are anti-periplanar conformation. The three-dimensional（3D） structure is stabilized by π···π stacking and hydrogen-bonding interactions to form a supramolecular self-penetrating network with 1D channels. In 1,there are voids 2999.7 ？~3 with 23.7% of per unit cell volume. Thermal analysis indicates that the framework of 1 is stable until 651 K and the photoluminescence of 1 in the solid shows very weak fluorescence at 382 and 560 nm upon excitation at 310 nm.

Two Nickel(Ⅱ) Complexes Constructed by Novel Bis(3-methoxy-2-pyridyl)ether-6,6′-dicarboxylic Acid Ligand:Lattice Water Control of Structure

Under given conditions, two complexes of [Ni（H20）2BEDA]·2H2O 1 and [Ni（Py）2- BEDA]·6H2O 2 （BEDA = bis（3-methoxy-2-pyridyl）ether-6,6′-dicarboxylic acid） have been synthesized and characterized by elemental analysis and X-ray single-crystal diffraction. Crystal data for 1： C14H18NiN2O11, monoelinic C2/c, a = 14.3844（17）, b = 12.9900（15）, c = 9.6309（11） A, β = 104.3350（10）°, V= 1743.5（4） A3, Z = 4, Dc= 1.711 g/cm^3, F（000） = 928, μ = 1.179 mm^-1, Mr= 449.01, the final R = 0.0228 and wR = 0.0625. Crystal data for 2： C24H32NiN4O13, triclinic P1, a = 9.423（2）, b = 11.863（3）, c = 13.089（3） A, α = 91.511（3）, β = 92.465（3）, γ = 100.696（2）°, V = 1435.6（6） A^3, Z = 2, Dc= 1.488 g/cm^3, F（000） = 672, μ = 0.748 mm^-1, Mr= 643.25, the final R = 0.0400 and wR = 0.0975. Interestingly, in the two complexes, lattice water molecules dominate its crystal structures. Therefore, extensive intermolecular hydrogen bonds assemble 1 and 2 into 2D extended sheets and a 3D open framework, respectively. Furthermore, water molecules present in 2 are associated to form water clusters.

非小细胞肺癌组织中circBIRC6、APPBP2表达及临床预后意义

目的 探讨非小细胞肺癌(NSCLC)组织中环状核糖核酸杆状病毒IAP重复序列6(circBIRC6)、β淀粉样蛋白前体蛋白结合蛋白2(APPBP2)表达及临床预后意义。方法 收集2018年6月~2020年1月90例在河北北方学院附属第一医院行手术切除的NSCLC组织及癌旁组织,采用实时荧光定量聚合酶链式反应检测circBIRC6、APPBP2表达,并分析二者与NSCLC患者临床病理特征的关系。通过Pearson相关性分析NSCLC组织中circBIRC6与APPBP2 mRNA表达的相关性,Kaplan-Meier法绘制不同表皮生长因子受体(EGFR)基因突变、TNM分期和circBIRC6、APPBP2 mRNA表达的NSCLC患者生存曲线,多因素Cox回归分析NSCLC患者预后的影响因素。结果 与癌旁组织比较,NSCLC组织中circBIRC6、APPBP2 mRNA表达升高(P<0.05)。NSCLC组织中circBIRC6与APPBP2 mRNA表达呈正相关(r=0.817,P<0.001)。NSCLC患者不同分化程度、TNM分期、淋巴结转移组织中circBIRC6、APPBP2 mRNA表达比较有差异(P<0.05)。随访3年,90例NSCLC患者总生存率为55.56%(50/90)。EGFR基因突变阳性/阴性NSCLC患者总生存率比较无差异(P>0.05);TNM分期Ⅰ~Ⅱ期NSCLC患者总生存率高于Ⅲ期NSCLC患者(P<0.05);circBIRC6、APPBP2 mRNA高表达组生存率低于circBIRC6、APPBP2 mRNA低表达组(P<0.05)。低分化、TNM分期Ⅲ期、淋巴结转移和circBIRC6≥10.97、APPBP2 mRNA≥2.48为NSCLC患者死亡的独立危险因素[OR(95%CI)=3.586(1.080~11.909)、3.632(1.193~11.057)、3.197(1.060~9.640)、3.223(1.086~9.570)、2.767(1.022~7.492)]。结论 NSCLC组织中circBIRC6、APPBP2 mRNA高表达,与分化程度、TNM分期、淋巴结转移和预后有关。

血清ADMA、IL-6、内毒素及乳酸在新生儿败血症所致感染性休克中的表达及临床意义

目的探讨血清不对称二甲基精氨酸(ADMA)、白细胞介素-6(IL-6)、内毒素及乳酸在新生儿败血症所致感染性休克中的表达及临床意义。方法选取我院收治的58例新生儿败血症所致感染性休克患儿为休克组,62例新生儿败血症未发生感染性休克患儿为败血症组,60例无感染新生儿为对照组。检测所有研究对象血清中的ADMA、IL-6、内毒素及乳酸水平。比较三组研究对象的ADMA、IL-6、内毒素及乳酸水平;分析ADMA、IL-6、内毒素及乳酸水平对新生儿败血症所致感染性休克患儿的诊断价值;分析ADMA水平与IL-6、内毒素及乳酸水平的关系;分析ADMA、IL-6、内毒素及乳酸水平与休克组预后的关系。结果休克组的ADMA、IL-6、内毒素及乳酸水平均高于败血症组及对照组(P<0.05);败血症组的ADMA、IL-6、内毒素水平均高于对照组(P<0.05);败血症组和对照组的乳酸水平无显著差异(P>0.05)。受试者工作特征曲线(ROC)结果显示,ADMA、IL-6、内毒素及乳酸诊断新生儿败血症所致感染性休克的曲线下面积(AUC)分别为0.93、0.89、0.89、0.92。Pearson相关性分析结果显示,ADMA水平与IL-6、内毒素及乳酸水平呈正相关(P<0.05)。ADMA、IL-6、内毒素及乳酸高水平与新生儿败血症所致感染性休克预后不良有关。结论血清ADMA、IL-6、内毒素及乳酸在新生儿败血症所致感染性休克中表达水平较高,可作为该疾病诊断的生物标志物并预测预后。

齐刺环跳穴干预坐骨神经损伤大鼠海马IL-1β、IL-6、TNF-α及GFAP表达影响的实验研究

目的 通过观察齐刺环跳穴对坐骨神经损伤大鼠海马白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor Necrosis Factor-alpha, TNF-α)及胶质纤维酸性蛋白(Glial Fibrillary Acidic Protein, GFAP)表达的影响,探讨齐刺环跳穴治疗坐骨神经痛的中枢镇痛机制。方法 60只SD大鼠随机分为假手术组、模型组、齐刺组、单刺组及药物组,每组12只,采用钳夹法制备大鼠坐骨神经损伤模型。造模第2天开始进行针刺及药物干预,连续14 d。观察各组大鼠干预前后坐骨神经功能指数(Sciatic nerve Function Index, SFI)、热缩足反射潜伏期(Paw Withdrawal Latency, PWL)的变化,ELISA法检测海马组织IL-1β、IL-6、TNF-α蛋白表达水平,实时定量PCR法及免疫组化法检测海马组织GFAP表达水平。结果 干预前,与假手术组比较,其余各组大鼠PWL值、SPI值显著降低(P<0.01),与模型组比较,齐刺组干预后大鼠PWL值、SPI值显著改善(P<0.01)。ELISA法、RT-PCR法及免疫组化检测结果显示,模型组、齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达较假手术组显著升高(P<0.01);与模型组相比,齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达显著下降,齐刺组表达低于单刺组及药物组(P<0.01)。结论 齐刺环跳穴缓解坐骨神经痛的镇痛机制可能与下调海马炎症因子表达,抑制星形胶质细胞活化,从而降低中枢痛觉敏化程度有关。

双标多测法在枣仁安神颗粒6个成分含量测定中的应用

目的建立枣仁安神颗粒中斯皮诺素、6'''-阿魏酰斯皮诺素、迷迭香酸、五味子醇甲、五味子乙素和丹酚酸B 6个成分的双标多测法,验证该方法在枣仁安神颗粒质量评价中应用的准确性和可行性。方法采用HPLC法,以乙腈为流动相A,0.2%冰醋酸溶液为流动相B,梯度洗脱,流速为1.0 mL·min^(-1),切换波长320 nm(斯皮诺素、6'''-阿魏酰斯皮诺素、迷迭香酸、丹酚酸B)、250 nm(五味子醇甲、五味子乙素),柱温28℃。采用5根不同的C_(18)色谱柱,测定枣仁安神颗粒6个成分的实际保留时间,计算各成分在各色谱柱保留时间的平均值,得到各成分的标准保留时间,选取斯皮诺素(峰1)、五味子乙素(峰6)作为双标化合物,使用双标线性校正法准确定位各成分色谱峰,预测成分在未知色谱柱的保留时间并进行方法学验证。以五味子乙素为参照物,计算其余各成分的相对校正因子,对各成分进行定量。结果双标线性校正法能够准确地预测待测组分在未知色谱柱上的保留时间;斯皮诺素、6'''-阿魏酰斯皮诺素、迷迭香酸、五味子醇甲和丹酚酸B相对于五味子乙素的相对校正因子分别为0.7342、0.6063、0.5664、0.9975及0.7773,其RSD均小于1%;各成分含量计算值和实测值无显著差异。结论双标多测法同时测定枣仁安神颗粒中6个成分可行且准确。

Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling

De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant.Our previous study found that histone deacetylase sirtuin 6(SIRT6)could be an ideal target for the treatment of cisplatin-induced acute kidney injury.In this study,we explored the protective effects of ellagic acid,a natural polyphenol compound that activates SIRT6,on cisplatin-induced nephrotoxicity.Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells.Moreover,ellagic acid ameliorated renal dysfunction,apoptosis and fibrosis induced by cisplatin in mice.Furthermore,ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin(IL)-1βand IL-6 expression both in vitro and in vivo.Mechanistically,ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor(TNF)-αexpression.And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis,indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation.Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury,and support ellagic acid as a potential adjunctive therapy for future cancer treatment.