18β-glycyrrhetinic acid inhibits proliferation of gastric cancer cells through regulating the miR-345-5p/TGM2 signaling pathway

BACKGROUND Gastric cancer(GC)is a common gastrointestinal malignancy worldwide.Based on cancer-related mortality,the current prevention and treatment strategies for GC still show poor clinical results.Therefore,it is important to find effective drug treatment targets.AIM To explore the molecular mechanism of 18β-glycyrrhetinic acid(18β-GRA)regulating the miR-345-5p/TGM2 signaling pathway to inhibit the proliferation of GC cells.METHODS CCK-8 assay was used to determine the effect of 18β-GRA on the survival rate of GES-1 cells and AGS and HGC-27 cells.Cell cycle and apoptosis were detected by flow cytometry,cell migration was detected by a wound healing assay,the effect of 18β-GRA on subcutaneous tumor growth in BALB/c nude mice was investigated,and the cell autophagy level was determined by MDC staining.TMT proteomic analysis was used to detect the differentially expressed autophagy-related proteins in GC cells after 18β-GRA intervention,and then the protein-protein interaction was predicted using STRING(https://string-db.org/).MicroRNAs(miRNAs)transcriptome analysis was used to detect the miRNA differential expression profile,and use miRBase(https://www.mirbase/)and TargetScan(https://www.targetscan.org/)to predict the miRNA and complementary binding sites.Quantitative real-time polymerase chain reaction was used to detect the expression level of miRNA in 18β-GRA treated cells,and western blot was used to detect the expression of autophagy related proteins.Finally,the effect of miR-345-5p on GC cells was verified by mir-345-5p overexpression.RESULTS 18β-GRA could inhibit GC cells viability,promote cell apoptosis,block cell cycle,reduce cell wound healing ability,and inhibit the GC cells growth in vivo.MDC staining results showed that 18β-GRA could promote autophagy in GC cells.By TMT proteomic analysis and miRNAs transcriptome analysis,it was concluded that 18β-GRA could down-regulate TGM2 expression and up-regulate miR-345-5p expression in GC cells.Subsequently,we verified that TGM2 is the target of miR-345-5p,and that overexpression of miR-345-5p significantly inhibited the protein expression level of TGM2.Western blot showed that the expression of autophagy-related proteins of TGM2 and p62 was significantly reduced,and LC3II,ULK1 and AMPK expression was significantly increased in GC cells treated with 18β-GRA.Overexpression of miR-345-5p not only inhibited the expression of TGM2,but also inhibited the proliferation of GC cells by promoting cell apoptosis and arresting cell cycle.CONCLUSION 18β-GRA inhibits the proliferation of GC cells and promotes autophagy by regulating the miR-345-5p/TGM2 signaling pathway.

Synthesis, Crystal Structure and DNA-Binding Property of a Mn(Ⅱ) Complex Based on 5-(Tri-fluoromethyl)pyridine-2-carboxylic Acid

A new complex Mn(Htpc)2(H2O)2(1, Htpc = 5-(trifluoromethyl)pyridine-2-carboxylic acid) has been synthesized and characterized by elemental analysis, IR, TG and single-crystal X-ray diffraction. 1 belongs to triclinic system, space group P■ with a = 5.0885(10), b = 6.5574(13), c = 14.016(3) ?, β = 90.67(3)o, V = 436.34(17) ?3, Z = 1, Dc = 1.793 g·cm-3, μ = 0.855 mm-1, Mr = 471.18, F(000) = 235, the final R = 0.0454 and wR = 0.1134 for 1998 observed reflections with I > 2σ(I). The Mn(Ⅱ) ion is coordinated by two N and two O atoms from two Htpc as well as two O atoms from two coordinated water molecules, forming a 0D motif with distorted octahedral coordinate geometry. The adjacent 0D units are linked into 1D chains through hydrogen bond O(1W)–H(1 WB)···O(2), and via the O(1 W)–H(1 WA)···O(1) hydrogen bond the neighboring 1D chains are connected into a 2D supramolecular layer. Moreover, the interactions between the ligand and its complex with CT-DNA were studied by EtBr fluorescence probe, which suggested that these compounds bind to CT-DNA through an intercalation mode. The binding constants were 0.41 and 0.64 for Htpc and complex 1, respectively. It indicates that the interaction between complex 1 and CT-DNA is stronger than Htpc.

Hydrothermal Syntheses and Crystal Structures of Six Complexes Constructed from 1,3,5-Benzenetricarboxylic Acid and 4'-(4-Pyridyl)-2,2':6',2''-terpyridine Mixed Ligands

Six new transition metal complexes, [Zn（HBTC）（PYTPY）]n·n PYTPY（1）, [Cu（HBTC）（PYTPY）]n·n PYTPY（2）, [Co（HBTC）（PYTPY）]n·n DMF（3）, [Mn（HBTC）（PYTPY）]n·n DMF（4）, [Cd（HBTC）（PYTPY）（H2O）]n·2nH2O（5）, and [Co（HBTC）（PYTPY）（H2O）2]（6）,（H3BTC = 1,3,5-benzenetricarboxylic acid, PYTPY = 4＇-（4-pyridyl）-2,2＇：6＇,2＇＇-terpyridine, DMF = N,N？-dimethylformamide）, have been synthesized and characterized by elemental analysis, IR and X-ray single-crystal diffraction. Complexes 1~5 all feature one-dimensional chain structures, and complex 6 exhibits a zero-dimensional structure. Complexes 1~5 present three-dimensional（3D） supramolecular frameworks via π-π stacking interactions, whenas 6 has also a 3D supramolecular structure assembled by hydrogen bonding. Meanwhile, complexes 1 ~ 6 exhibit the thermal stabilities and photoluminescent properties.

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.

Synthesis,Crystal Structure,and Magnetic Property of One 3D Nickel Coordination Polymer Based on 2-Hydroxy-5-(3',5'-terephthalic acid)Pyridine and 1,4-Bis(1-imdazoly)benzene

One novel nickel coordination polymer, {[Ni（OTP）（bib）1.5（H2O）]·2H2O}n（1, H2 OTP = 2-hydroxy-5-（3＇,5＇-terephthalic acid） pyridine, bib = 1,4-bis（1-imdazoly）benzene）, has been synthesized and characterized by elemental analysis（EA）, IR, powder X-ray diffraction（PXRD）, and thermogravimetric（TG） analyses. The crystal of 1 crystallizes in monoclinic, space group P21/n with a = 12.2860（5）, b = 13.8246（6）, c = 19.0140（8） A, β = 104.3870（1）°, V = 3128.2（2） A3, Z = 4, C32H28N7 Ni O8, Mr = 697.32, Dc = 1.481 g/cm^3, F（000） = 1444 and μ（Mo Kα） = 0.684 mm-1. The final R = 0.0704 and w R = 0.1764 for 5485 observed reflections with I 2σ（I） and R = 0.1087 and wR = 0.2010 for all data. Topology analysis reveals that complex 1 is a 3D 2-fold interpenetrated {4^4·6^6}-nov net based on the 1D [Ni（OTP）]n chain and the 2D [Ni2（bib）3]n sql sheet. And the variable-temperature magnetic susceptibility measurements exhibit weak antiferromagnetic coupling interaction.

2-(四氮唑偶氮)-5-二乙氨基苯甲酸光度法测定铜

研究了新显色剂2 (四氮唑偶氮) 5 二乙氨基苯甲酸(TTZDBA)与铜显色反应的条件。结果表明,在pH4 0的HAc NaAc缓冲溶液中,TTZDBA与Cu2+形成稳定的紫红色络合物,其最大吸收波长在570nm处,表观摩尔吸光系数为4 08×104,Cu2+质量浓度在0～0 4mg/L范围内符合比尔定律。所拟方法可不经分离直接测定镁合金和铝合金标样中的微量铜,加标回收率100 8%～102 1%,RSD(n=6)在1 8%～4 2%,结果令人满意。

2-(四氮唑偶氮)-5-二乙氨基苯甲酸的合成及光度法测定钒

研究了新显色剂2 (四氮唑偶氮) 5 二乙氨基苯甲酸(简称TTZDBA)的合成。经元素分析、红外光谱、紫外光谱、核磁共振谱等方法测试确定其组成和结构。研究了试剂的性质及其与钒的显色反应的条件,建立了光度法测定钒的新方法。在pH3.5的HAc NaAc介质中,TTZD BA与V(Ⅴ)形成摩尔比为2∶1的紫红色配合物,配合物至少稳定18h,其最大吸收波长在566nm处,表观摩尔吸光系数为3.52×104L·mol-1·cm-1,V(Ⅴ)质量浓度在0～0.8mg/L内遵守比尔定律。经标样分析验证,结果与标准值相符,加标回收率为101.3%～102.8%,RSD(n=6)在1.0%～2.5%。所拟方法可不经分离直接测定铝合金样品及合成废水中的钒。

Pig Liver Esterase-catalyzed Hydrolysis of Three Diesters of meso-Bicyclic Dicarboxylic Acid and Three Tetraesters of Tetrahydrofuran -2,3,4,5-tetracarboxylic Acid

Three diesters of exo- syn-meso-oxabicyclo (2, 2, 1 ) -hept- 5- ene- 2, 3- dicarboxylic acid and three tetraesters of tetrahydrofuran-2, 3, 4, 5-tetracarboxylic acid were synthesized and tested with enantioselective hydrolysis catalyzed by pig liver esterase(PLE). The results of the PLEcatalyzed hydrolysis were discussed.

2-(四氮唑偶氮)-5-二乙氨基苯甲酸指示剂络合滴定法测定钴

探讨 2 (四氮唑偶氮 ) 5 二乙氨基苯甲酸 (TTZDBA)作为络合滴定钴的指示剂的分析性能。在pH值为 7.0的NH3 ·H2 O -NH4Ac缓冲溶液中 ,加入 5滴TTZDBA作指示剂 ,用EDTA标准溶液进行滴定 ,滴定终点溶液的颜色变化敏锐 ,由紫红色变为亮橙色。将该方法用于试剂和钴基合金样品中钴的测定 ,测定结果与标准值相符 ,RSD(n =6 )为 0 .38%～ 1.5 2 %。

Synthesis of 9-(5-Pentyl-2-furyl)nonanoic Acid

Naturally occurring 9-(5-pentyl-2-furyl) nonanoic acid which was synthesized through five steps in about 20% overall yield by using 5-trimethylsilyl-2-furancarboxaldehyde as a starling material.

Synthesis of (S)-2-(3-Arylacrylamido)-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)ethoxy]phenyl}propanoic Acids

The synthesis of （S）-2-（3-arylacrylamido）-3-{4-[2-（5-methyl-2-phenyloxazol-4-yl）etho- xy]phenyl}propanoic acids is described. Their structures were confirmed by ^1H-NMR.

Syntheses and antimicrobial activities of amide derivatives of 4-[(2-isopropyl-5-methylcyclohexyl)oxo]-4-oxobutanoic acid

Chiral 4-[(2-isopropyl-5-methylcyclohexyl)oxo]-4-oxobutanoic acid reacts with substituted anilines to produce amides 1-6 in high yields. Resulted amides 1-6 were investigated for their antifungal and antibacterial activities. Compounds 2 (96.5%) against Aspergillus fumigatus and 6 (93.7%) against Helminthosporium sativum demonstrated excellent activities. However, compounds 3 (37.6%) against Bacillus subtilis, 4 (33.2%) against Pseudomonas aurignosa, 5 against Klebsiella pneumonia demonstrated excellent growth inhibition potential.

Effect of Temperature on the Reaction of 2-(N-acetylamine)-3-(3,5-di-<i>tert</i>-butyl-4-hydroxyphenyl)-propionic Acid with Oxygen in an Alkaline Condition

Results of oxidation 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid oxygen depend on temperature. At 55℃?- 60℃, 2,4-di-tert-butylbicyclo(4,3,1)deca-4,6-dien-8-(N-acetylamine)-3,9-dion-1-oxa is formed. The constitution is based on dates of spectrums 1Н and 13С NMR. At 95℃?- 97℃, mixtures of 2,4-di-tert-butylbicyclo(4,3,1)deca-4,6-dien-8-(N-acetylamine)-3,9-dion-1-oxa and of 6,8-di-tert-butyl-3-(N-acetylamine)spiro(4,5)deca-1-oxa-5,8-dien-2,7-dione are produced. Structures are calculated by the method of Hartrii-Foka. Values of enthalpies and of entropies allow to assume dynamic isomerism.

Syntheses, Crystal Structures and Properties of Two Metal-organic Complexes Based on 5-(4-Pyridyl)-methoxyl Isophthalic Acid

Two new metal-organic frameworks, [Co3L2（NO2）2（H2O）2],, （1） and{[Ni（L）（H2O）5] （H2O）2.DMF}, （2, H2L = 5-（4-pyridyl）-methoxyl isophthalic acid）, have been synthesized by the hydrothermal method and characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis （TGA） and X-ray crystallography. Compound 1 crystallizes in the monoclinic system with space group P2/c and adopts a slightly distorted octahedral configuration. In compound 1, the 2D bilayered structures are linked by O-H...O and O-H...N hydrogen bonds to form a 3D framework. Compound 2 crystallizes in the monoclinic system with space group P2/n, and the central nickel atoms are octa-coordinated with five O atoms from coordinated water molecules and one N atom from one H2L ligand. The abundant O-H…O hydrogen bonds and π…π interactions link the molecules into a 3D framework. In addition, compounds 1 and 2 exhibit strong ultraviolet absorption in the solid state at room temperature.

A Zn(Ⅱ) Coordination Polymer Based on a Flexible Polycarboxylate Ligand 5-(4-Hydroxypyridinium-1-ylmethyl)-isophthalic Acid: Synthesis, Structure, and Property

A Zn（Ⅱ） supramolecular coordination polymer, {[Zn2（L）2（m-bix）（H20）]6H2O}n（1）, with an interesting 1D→2D polythreading array from a flexible and angular organic aromaticpolycarboxylate ligand 5-（4-hydroxypyridinium-l-ylmethyl）isophthalic acid （H2L）, and N-donorligand 1,3-bis（imidazol-l-ylmethyl）benzene （m-bix）, has been obtained under hydrothermalconditions and characterized by elemental analysis, powder X-ray diffraction （PXRD）, IR, thermalgravimetric analyses （TGA） and single-crystal X-ray diffraction. In 1, the Zn（Ⅱ） center has twocoordination geometries. One exhibits a trigonal bipyramidal coordination sphere, and the other isa tetrahedral geometry; L2- has two different coordination modes, with one connecting three Zn（Ⅱ）ions through two monodentate carboxylate groups and the monodentate hydroxyl group, and theother bridging two Zn（Ⅱ） ions through two carboxylate groups. The L2- anions connect the Zn（Ⅱ）centers forming an infinite 1D tubular structure. These 1D tubes are interconnected by the m-bixspacers to form a 2D framework. Such 2D layers are further assembled into a 3D supramolecularnetwork via hydrogen bonds. Meanwhile, the luminescent property of 1 has also been investigatedin detail.

A Y(Ⅲ)-organic Coordination Polymer Constructed from 2-(Pyridine-4-yl)-1H-imidazole-4,5-dicarboxylate and Oxalate Ligands: Structure and Luminescent Property

A novel compound, {[Y（HPIDC）（OX）1/2（H2O）]·2H2O}n （1, H3PIDC = 2-（pyridin-4- yl）-1H-imidazole-4,5-dicarboxylic acid, H2OX = oxalic acid）, has been synthesized under hydrothermal conditions and characterized by thermal analysis （TGA）, powder X-ray diffraction （PXRD）, and single-crystal X-ray diffraction. Complex 1 crystallizes in monoclinic space group P21/c with a = 8.342（8）, b = 14.61（1）, c = 11.487（1）, β = 90.78（9）°, V = 1400.4（2）3, Z = 4, C11H11N3O9Y, Mr = 418.14, Dc = 1.983 g/cm3, F（000） = 836, Rint = 0.0509, T = 293（2） K, μ = 4.240 mm-1, the final R = 0.0477 and wR = 0.1125 for 2770 observed reflections with I 2σ（I）. Compound 1 exhibits a 3D framework and generates the 1D open channels filled with free water molecules. The structure of 1 can be rationalized as a diamondoid network when the atom yttrium is regarded as a 4-connected node linking four surrounding yttrium atoms. The luminescent property of compound 1 is also investigated.

Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats

Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D（-）-2-amino-5-phosphonopentanoic acid（AP-5）,or both once daily for 15 days.Compared with injured drug na？ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity（as assessed by immunohistochemistry） and protein（as determined by western blot assay） in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.

Synthesis and Crystal Structure of a 2D Sm(Ⅲ) Coordination Polymer: {[Sm_2L_3(H_2O)_4]·(4,4?-bpy)·3H_2O}_n

A new compound, {[Sm^2L3（H2O）4]·（4,4＇-bpy）·3H2O}n（1, H2 L = 5-（3-pyridyl methoxy） isophthalic acid, 4,4＇-bpy = 4,4A-dipyridyl）, has been hydrothermally synthesized and characterized by single-crystal X-ray diffraction. It crystallizes in triclinic, space group P1 with a = 11.266（2）, b = 15.530（3）, c = 16.711（3） A, α = 112.803（3）, β = 90.526（1）, γ = 94.006（3）°, V = 2686.6（9） A3, Z = 2, Dc = 1.727 g/cm^3, μ = 2.251 mm-1, F（000） = 1392, S = 0.999, the final R = 0.0296 and wR = 0.1058. In the title compound, two crystallographically independent Sm^3＋ cations are bridged by the carboxyl group of L2- ligands to form two different {Sm^2} binuclear subunits which are further connected by two distinct L2- ligands to shape a 1D chain, and such 1D chains are linked up to generate a 2D coordination polymer by another crystallographically unique L2- ligand. The thermogravimetric analysis and luminescent property of the title compound were also investigated.

Hydrothermal Syntheses and Crystal Structures of Three Lanthanide(Ⅲ)Complexes Based on Carboxyl Derivatives of 1,10-Phenanthroline

Three lanthanide（III） complexes [Ln（4-NCP）（1,4-BDC）]n·xn H2O（Ln = Pr（1）, Sm（2）, Nd（3）. 4-HNCP = 2-（4-carboxyphenyl）imidazo（4,5-f）（1,10）phenanthroline, 1,4-H2 BDC = benzene-1,4-dicarboxylic acid） have been hydrothermally synthesized and characterized via elemental analysis, infrared spectrometry and single-crystal X-ray diffraction. Structural analyses revealed that complexes 1~3 possess similar porous three-dimensional frameworks with the point symbol {4^（12）·6~3}. Meanwhile, complexes 1~3 exhibit excellent thermal stabilities and complex 2 exhibits characteristic luminescent property.

Synthesis of Folate-Appended <i>β</i>-Cyclodextrin Using Phenanthroline as Linker for Cancer Targeting Drug Delivery

Here we have synthesized cancer targeting drug delivery system that contains β-cyclodextrin as a drug carrier and folic acid as a targeting ligand. Folic acid was selected as a cancer targeting ligand because folic acid receptors are highly expressed in a variety of tumor types. β-cyclodextrin and folic acid were connected through a linker [1,10-phenanthroline or 5-(hydroxymethyl) furfural]. β-cyclodextrin and folic acid were attached to the linker by formation of Schiffbase and ester, respectively. Our targeted synthetic products were confirmed by NMR, Mass and IR spectroscopy. We anticipate that our synthetic products can confer cancer cell-specific drug delivery as well as desired properties such as nanoparticle formation.