pH Dependent Supramolecules Based on Co-crystallization of Pyrazine-2,3,5,6-tetracarboxylic Acid with 4,4＇-Bipyridine through Intermolecular Hydrogen Bonds

Co-crystallization of pztcH_4 with 4,4＇-bipyridine（4,4＇-bipy） in pH = 3-4 and 1-2 gave two new binary molecular adducts： [（4,4＇-bipy H2）（pztc H2）]（1） and [（4,4＇-bipy H2）（pztcH3）（Cl）]·4H2O（2）, respectively. Compounds 1 and 2 have been characterized by IR, elemental analysis, NMR and X-ray single-crystal diffraction. Compound 1 crystallizes in triclinic, space group P1 with a = 5.7752（12）, b = 7.9126（16）, c = 9.4492（19） ？, α = 97.49（3）, β = 107.71（3）, γ = 94.52（3）o, V = 404.62（14） A^3, Z = 1, μ = 0.137 mm^1, Dc = 1.692 Mg/m^3, C18H12N4O8, Mr = 412.32, F（000） = 212, S = 1.025, R = 0.0360 and wR = 0.0973. Compound 2 crystallizes in monoclinic, space group C2/c with a = 17.093（3）, b = 7.7665（16）, c = 18.414（4） A, β = 113.36（3）o, V = 2244.1（8） A^3, Z = 4, μ = 0.244 mm^-1, Dc = 1.542 Mg/m^3, C18H21ClN4O12, Mr = 520.84, F（000） = 1080, S = 1.021, R = 0.0343 and wR = 0.0978. In compound 1, pztc H22- anions self-formed 2-D sheets by strong Oacid-H···Oacidhydrogen bonds, which are further extended to form a 3-D supramolecular network bridged with 4,4？-bipy via N-H···Oacid interactions. In compound 2, besides the 1-D chain constructed by pztc H3-itself through strong H-bond Oacid-H···Oacid, the other chain is constructed with 4,4？-bipy H22＋, Cl-anion and water molecules by moderate H-bonds and Ow-H···Cl and N-H···Ow. The two chains are linked with μ3-connected water molecules resulting from the combination of strong synthon-assisted H-bonding Oacid-H···Ow to afford an interlaced 3-D network.

A Hydrogen Bond Stabilized 3D Network Built from Pyrazine-2,3,5,6-tetracarboxylic Acid and 8-Hydroxyquinoline

8-Hydroxyquinoline salt of pyrazine-2,3,5,6-tetracarboxylic acid [HQ]2[H2pztc]· 2H2O （1） was prepared and characterized by single-crystal X-ray diffraction, NMR, IR, TGA, elemental analysis and fluorescent measurements. Compound 1 crystallizes in orthorhombic, space group Pbcn with a = 9.953（3）, b = 15.966（3）, c = 16.081（5） A, V = 2555.5（13） A3, Z = 4, μ = 0.122 mm^-1, Dc = 1.514 Mg/m3, T= 296（2） K, C26H22N4O12, Mr = 582.48, F（000） = 1208, S = 1.006, R = 0.0448 and wR = 0.1149. Compound 1 has a three-dimensional （3D） network, in which pyra- zine-2,3,5,6-tetracarboxylic acids build up two-dimensional （2D） sheets and 8-hydroxyquinoline cations and water molecules act as pillars to connect the 2D sheets into an extended 3D network through strong intermolecular hydrogen bonding and π…π stacking interactions. Especially, a very short O-H…O hydrogen bond （O…O 2.470（2） A） between two neighboring [H2pztc] anions was observed.

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.

Hydrothermal Synthesis and Crystal Structure of One 3D Coordination Polymer of Cobalt(II) Achieved from 1,1′-Biphenyl-2,2′,6,6′-tetracarboxylic Acid Ligand

A new three-dimensional coordination polymer {[Co（BPTC）0.5（bix）]′（H2O）}n （1, H4BPTC = 1,1′-biphenyl-2,2′,6,6′-tetracarboxylic acid, bix = 1,3-bis（imidazol-l-ylmethyl）-benzene） has been synthesized by the hydrothermal method and characterized by IR, elemental analysis, and single-crystal X-ray analysis. The crystal is of orthorhombic, space group Pbcn with a = 13.2975（10）, b = 13.8424（12）, c = 22.6367（17） A, CoC22H19N4Os, Mr = 478.34, V = 4166.7（6） A3, Dc = 1.525 g/cm^3, F（000） = 1968,μ = 0.867 mm^-1, S = 1.023 and Z = 8. The final R = 0.0683 and wR = 0.1529 for 3655 observed reflections with I 〉 20（I）. In the title complex, the 2D Co-BPTC layer is formed through self-assembly of Co（II） ions and bridging BPTC4-ligands in a molar ratio of 2：1. The metal-organic lattice layers are further united together through the second bridging ligand bix to form a 3D metal-organic framework. The thermal stability of the title complex was studied by thermal gravimetric （TG） and differential thermal analysis （DTA）.

A Three-dimensional Ba(Ⅱ) Coordination Polymer Based on H_4AQTC(Anthraquinone-1,4,5,8-tetracarboxylic Acid): Quinone Oxygen Atoms Participate in Coordination

A novel coordination polymer [Ba2（AQTC）（H2O）3]n（1, H4 AQTC = anthraquinone-1,4,5,8-tetracarboxylic acid） has been prepared under hydrothermal conditions and characterized by single-crystal X-ray diffraction, elemental analysis, infrared spectroscopy and thermogravimetric analysis. Two quinone oxygen atoms and all carboxylate oxygen atoms of AQTC4- are involved in coordination. Two equivalent barium ions are mainly linked by carboxylate oxygen atoms into a dimer. Neighbouring dimers are further connected by the AQTC4- ligand through carboxylate oxygen atom, leading to a 1-D chain structure. Every two adjacent chains are mainly further connected by face carboxylate oxygen atoms and water molecule, generating a two-dimensional layer structure. Such 2-D layer structures are connected with O（6） and O（6C） atoms from water molecules to form a 3-D structure. In addition, luminescent properties of 1 are also investigated.

Synthesis and Crystal Structure of One Mixed-ligand Coordination Polymer Based on the Novel Terphenyl-2,5,2',5'-tetracarboxylic Acid Ligand

Solvothermal reaction of aromatic terphenyl-2,5,2＇,5＇-tetracarboxylic acid （Hnqptc） ligand and the transitional metal cation of Mn11 in the presence of 3-（2-pyridyl）pyrazole （pp） affords one new coordination polymer, [Mn（qptc）0.5（pp）2]n·n（H2O） （1）. The structure has been determined by single-crystal X-ray diffraction analyses and further characterized by elemental analyses, IR, TGA, and magnetism. The carboxyl groups of qptc4 exhibit a μ1-η1：η0 coordination mode, and the qptc4- acts as a H-shaped ligand linking the Mn11 centers together to form a 2D polymeric [Mn（qptc）0.5]n layer. The crystal of 1 crystallizes in orthorhombic, space group Pbca with a = 9.3119（12）, b = 20.848（3）, c = 26.134（3） A, V= 5073.4（11） A3, Z= 8, C27HIgMnN6O5,Mr=562.42, Dc = 1.473 g/cm3, F（000） = 2304 and μ（MoKa） = 0.571 mm-1. The final R = 0.0468 and wR = 0.1196 for 4429 observed reflections with I 〉 2σ（I） and R = 0.0797 and wR = 0.1383 for all data.

Hydrothermal Synthesis and Crystal Structure of a Manganese(II) Coordination Polymer with 1,1′-Biphenyl-2,2′,6,6′-tetracarboxyl Acid and 2,2′:6,2′′-Terpyridine Ligands

The title compound {[Mn（H2BPTC）（tpy）（H2O）]·（H2O）3}, （1, H4BPTC = 1,1＇- biphenyl-2,2＇,6,6＇-tetracarboxylic acid, tby = 2,2＇：6,2＇-terpyridine） has been synthesized by the hydrothermal reaction, and its structure was determined by X-ray diffraction and characterized by elemental analysis, IR spectrum and thermogravimetric analysis. The crystal is of monoclinic, space group P21/c with a = 10.971（2）, b = 20.776（4）, c = 14.332（3） A, β = 109.25（3）°, MnC31H27N3O12, Mr = 688.50, V= 3084.1（10） A^3, Dc = 1.483 g/cm^3, F（000） = 1420, p = 0.498 mm^-1, S = 1.066 and Z = 4. The final refinement gave R = 0.0447 and wR = 0.1103 for 5107 observed reflections with I 〉 2σ（I）. The title complex has a {[Mn（H2BPTC）（tpy）（H2O）]}, chain structure, and the hydrogen bonding interactions make it more stable. Each chain is further connected to the adjacent ones through π…π, C-H…π and rich hydrogen bonds to form a metal-organic coordination polymer.

Hydrothermal synthesis and structural studies of a new coordination polymer of lanthanum(Ⅲ) with benzene-1,2,4,5-tetracarboxylic acid and 4,4′-bipyridine

A new lanthanum complex formulated as {（bpyH2）[La（btc）（H2O）4（NO3）]·2H2O}n （1） （btcH4=benzene-1,2,4,5-tetracarboxylic acid; bpy=4,4＇-bipyridine） was hydrothermally synthesized. The complex was characterized by FT-IR spectroscopy, elemental analysis and X-ray diffraction. X-ray crystal structural analysis revealed that the compound belonged to the monoclinic space group C2/c with cell parameters a= 1.42806（7） nm, b=1.10258（5） nm, c=1.60333（8） nm and β=101.9400（10）°. The complex was polymeric with La^III atoms linked by four O atoms from two carboxylate groups of one benzene-1,2,4,5-tetracarboxylate. The LaIn atom was ten coordinated in a distorted tetracapped trigonal prism. In the crystal structure, a wide range of noncovalent interactions consisting of hydrogen bonding （of the types of O-H…O, N-H…O and C-H…O） and ion pairing interactions connected the various components into a supramolecular structure.

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.

基于柔性苯二乙酸CM6@Zn-MOF纳米材料的构筑和光电性能研究

金属有机框架(Metal-organic frameworks,简称MOFs)作为有效能量转移的供体,在人工光采集材料领域中已引起许多专家的关注。特别是二维MOFs纳米片,因每个活性位点暴露在外易靠近受体,可以有效地将内部能量转移给外部受体,具有更为非凡的光电性能。通过选用柔性的1,2-苯二乙酸(H_(2)opda)和刚性的3,5-二(三氮唑)吡啶(btyp)作为有机配体,合成了一种新型的二维配位聚合物[Zn_(3)(btyp)_(2)(opda)_(3)(H_(2)O)_(3)]·(btyp)(H_(2)O)_(3)(Zn-MOF),晶体属于三斜晶系、P-1空间群。在该晶体结构中,反式opda配体的2个羧基均以双齿螯合模式与Zn(Ⅱ)离子配位,形成一维无限链;btyp配体桥链支撑相邻一维链,构成二维网面;通过opda羧基O与结晶H_(2)O之间多个O—H…O的相互作用形成三维超分子网络结构。Zn-MOF且具有完整的循环伏安曲线(还原、氧化电位分别为-0.22、0.05 V),良好的扫描速率。使用超声粉碎法将Zn-MOF层状结构剥离形成二维纳米片,再与香豆素6(CM6)掺杂形成CM6@Zn-MOF纳米材料,荧光从蓝光向绿光移动,将光收集范围从紫外光扩展到可见光,加之良好的电化学循环伏安性能(还原、氧化电位分别为-0.21、0.08 V),有望成为光电应用新材料。

Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

全氟辛烷磺酸新型替代物6:2氟调聚磺酸/盐的环境检测及毒性研究进展

全氟辛烷磺酸(perfluorooctane sulfonate,PFOS)是全氟和多氟烷基化合物(per-and polyfluoroalkyl substances,PFASs)的代表物质,因其生物累积性、环境持久性以及潜在的致癌风险,于2009年被列入《斯德哥尔摩公约》的管控名单.随着PFOS的生产和使用受到国际社会的严格限制,6:2氟调聚磺酸/盐(6:2 fluorotelomer sulfonic acid/sulfonate,6:2 FTSA)作为其替代品,在全球范围内分布日益广泛,对生态环境构成了新的威胁,被认为是一种潜在的新型污染物.尽管如此,目前对6:2 FTSA的研究仍处于起步阶段,相关科学知识体系亟待完善.本文系统性地综述了6:2 FTSA的检测技术、环境分布、生物毒性及其作用机制,以及转化与降解方面的最新研究进展.重点分析了6:2 FTSA的检测方法、生物毒性机制研究的现状,以及降解工艺的开发与优化.通过对这些关键问题的剖析,揭示了当前研究领域面临的挑战,并展望了未来可能的研究方向,为评估6:2 FTSA作为PFOS替代品的合理性提供理论基础与实验依据.

Crystal Structure,Thermal Behavior and Magnetic Properties of a New Copper(Ⅱ) Complex Based on Biphenyl-2,5,2',5'-tetracarboxylic Acid

A new coordination polymer,[Cu2（bptc）（2,2＇-bpy） 2（H2O）]·H2O（2,2＇-bpy = 2,2＇-bipyridine,H4bptc = biphenyl-2,5,2＇,5＇-tetracarboxylic acid） ,has been synthesized under hydrother-mal conditions. The structure was characterized by single-crystal X-ray diffraction,elemental analysis,IR spectra and thermogravimetric analysis. It crystallizes in triclinic,space group P1 with a = 10.6447（12） ,b = 11.0191（12）,c = 16.1253（18）A,α = 79.538（2）,β = 88.0720（10） ,γ = 61.6650（10） °,V = 1634.1（3） A^3,C36H26Cu2N4O10,Mr = 801.69,Z = 2,Dc = 1.629 g/cm^3,μ（MoKα） = 1.370 mm^-1,F（000） = 816.0,R = 0.0418 and wR = 0.1135 for 4416 observed reflections with I 〉 2σ（I） . X-ray analysis shows that the title complex exhibits 1D wavelike [Cu2（bptc） ]n chains with two types of diamond-shaped pores. These 1D chains are linked into a 3D supramolecular structure via O-H···O,C-H···O interactions and weak π···π stacking interactions. There exist H-bonded helices in a right-and left-handed sequence by turns in a 2D layer. Moreover,thermal stability has been studied and magnetic measurements show antiferromagnetic interactions for this complex.

A 3D-QSAR Study on C-3 Substituted 4,6-Dichloroindole-2- Carboxylic Acids with Comparative Molecular Field Analysis

Aim and Method Comparative molecular field analysis (CoMFA), a threedimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a novelseries of C-3 substituted 4, 6-dichloioindole-2-carboxylic acids to study the relationship betweentheir structure and the affinity for the glycine site of the NMDA receptor. Result Hie coefficientsof cross-validation q^2 and non cross-validation r^2 for the model established by the study are0.744 and 0.993, respectively, the value of variance ratio F is 261.343, and standard error estimate(SE) is 0.039. Conclusion These values indicate that the CoMFA model may have a good prediction forthe activity of C-3 substituted 4, 6-dichloroin-dole-2-carboxylic acids. As a consequence, thepredicted activity values of new designed compounds supports our conclusion from the model.

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。

Gallic acid与DA-6强化黑麦草修复复合重金属(Cd、Pb、Cu、Zn)污染土壤的研究

用盆栽实验研究了Gallic acid与DA-6单独及耦合使用对黑麦草修复复合重金属污染土壤的影响。结果表明,Gallic acid与DA-6单独及耦合使用,能使黑麦草对重金属污染土壤中Cd、Zn的修复产生明显的促进作用,但对Pb、Cu的修复没有明显变化。当添加5 mmol/kg的Gallic acid时,黑麦草对Cd、Zn的富集量分别达到了15.9 mg/kg与1 660.8 mg/kg,富集系数较未添加Gallic acid时提高了93.9%,233.9%;同时添加10μmol/kg DA-6与5 mmol/kg Gallic Acid之后,黑麦草对Cd、Zn的富集量分别达到了18.8 mg/kg,1 680.5 mg/kg,富集系数较未添加DA-6时提高了18.2%与1.2%。

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。

Lactic Acid Reduces LPS-Induced TNF-a and IL-6 mRNA Levels Through Decreasing I?Ba Phosphorylation

This study explored the effects over time of lactic acid （LA） on IκBα phosphorylation and nuclear factor-kappa B （NF-κB） p65 protein expression, and on tumor necrosis factor a （TNF-α） and interleukin-6 （IL-6） mRNA levels in rat intestinal mucosa microvascular endothelial cells （RIMMVECs） stimulated by lipopolysaccharide （LPS）. I？Ba, phosphorylated IκBa （p-IκBa） and p65 protein levels were monitored by Western blot analysis, and TNF-a and IL-6 mRNA levels were analyzed using real-time PCR. LA treatment reduced TNF-a and IL-6 mRNA levels in LPS-stimulated RIMMVECs, with the greatest effect being after 3 h. The highest inhibitory effect of LA on IκBa phosphorylation to prevent activation of NF-κB was after 6 h. These results suggest that LA reduces TNF-a and IL-6 mRNA levels through decreasing IκBa phosphorylation and blocking the dissociation of IKK complex, which prevents activation of NF-κB.

Influence of gallic acid on porcine neutrophils phosphodiesterase 4,IL-6,TNF-α and rat arthritis model

Our previous studies showed that the anti-inflammatory effects of Paeonia lactiflora roots extract may be mediated, at least in part, through its gallic acid content, and this effect may be regulated in part by an inhibition on c AMP-phosphodiesterase（PDE）. To explore the anti-inflammatory effect and mechanism, the influence of gallic acid on neutrophils PDE4 activity and expression, TNF-α and IL-6 content and rat arthritis model were further studied. PDE4 activity and gene express were calculated respectively by substrate c AMP change examined with HPLC and real-time RT-PCR. The concentration of IL-6 and TNF-α in supernatant were assayed by ELISA method. Model of rat arthritis was caused by complete Freund＇s adjuvant. Results showed that gallic acid had a dose-dependent restraint on PDE4 activity of neutrophils in vitro, promoted significantly PDE4 A expression（P〈0.01）, and had no influence on the expressions of PDE4 B and 4D. However, PDE4 C expression was not detected. Gallic acid could promote IL-6 release（P〈0.05）, and inhibit TNF-α release of neutrophils（P〈0.05）. The experiment in vivo showed that gallic acid had obvious restraint on local inflammation of animal model（P〈0.05）. Therefore, the anti-inflammatory effect of gallic acid may be mediated in part through an inhibition on PDE4 activity and further an increase of IL-6 and a decrease of TNF-α of neutrophils, and this effect seemed to have no relationship with PDE4 expression.

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。