Reactive oxygen species-mediated unfolded protein response pathways in preimplantation embryos.

Excessive production of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress-mediated responses are critical to embryonic development in the challenging in vitro environment. ROS production increases during early embryonic development with the increase in protein requirements for cell survival and growth. The ER is a multifunctional cellular organelle responsible for protein folding, modification, and cellular homeostasis. ER stress is activated by a variety of factors including ROS. Such stress leads to activation of the adaptive unfolded protein response (UPR), which restores homeostasis. However, chronic stress can exceed the toleration level of the ER, resulting in cellular apoptosis. In this review, we briefly describe the generation and impact of ROS in preimplantation embryo development, the ROS-mediated activation mechanism of the UPR via the ER, and the subsequent activation of signaling pathways following ER stress in preimplantation embryos.

Effect of potential role of p53 on embryo development arrest induced by H2O2 in mouse.

During mammalian embryo development in vitro, mechanism of embryonic development arrest caused by oxidative stress has not been clear so far. The tumor suppressor protein p53 controls cell cycle and programmed cell death by regulating relevant signal pathway. Recent researches revealed that the concentration and distribution of p53 are closely related with reactive oxygen species (ROS). The main objective of this experiment was to explore the role of p53 on embryonic development arrest caused by oxidative stress. Results showed that embryo arrest at two-four-cell stage was significantly increased in the presence of 50 µM H2O2 (39.01 ± 2.74 vs. 77.20 ± 5.34%, p < 0.05). Supplementation of N-acetyl-L-cysteine (NAC) obviously reduced the ratio of development arrest (39.01 ± 2.74 vs. 71.18 ± 5.34%, p < 0.05), which was accompanied by an increase in ROS level, and H2O2 treatment sharply increased messenger RNA (mRNA) expression and protein levels of p53 and p53-ser15. Further increased transcription of GADD45a and p21, a downstream of p53, has an especially significant effect on the mRNA expression of GADD45a. However, expressions of cdc2 were reduced by H2O2. In addition, using Pifithrin-α (PFT-α), the suppresser of p53, the result showed that GADD45a and p21 were significantly downregulated, but the cell cycle gene cdc2 was significantly upregulated, while the protein level of p53 and p53-ser15 was significantly decreased. Taken together, these results demonstrate that ROS could activate p53 and regulate p53 target genes to influence early embryo development in in vitro culture.

Aqua-(1,10-phenanthroline-κN,N')bis-(trimethyl-acetato)-κO,O';κO-cobalt(II).

In the title compound, [Co(C(5)H(9)O(2))(2)(C(12)H(8)N(2))(H(2)O)], the Co(II) atom is coordinated in a distorted octahedral environment by three carboxyl O atoms of two trimethyl-acetate ligands, one aqua O atom and two N atoms from 1,10-phen-anthroline. The crystal structure is stabilized by O-H⋯O hydrogen bonds and π-π stacking inter-actions [inter-planar distance between inter-digitating 1,10-phenanthroline ligands = 3.378 (2) Å].

Bis[µ-3-(2-hydroxy-ethyl)-2-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-olato-κN,O:O]bis[aquachloridocopper(II)].

In the dinuclear centrosymmetric copper(II) title compound, [Cu(2)(C(11)H(11)N(2)O(2))(2)Cl(2)(H(2)O)(2)], each Cu(II) ion has a slightly distorted trigonal-bipyramidal geometry and is coordinated by one N and one O atom from one 3-(2-hydroxy-ethyl)-2-methyl-4-oxopyrido[1,2-a]pyrimidin-9-olate ligand, another O atom from the second ligand, one water mol-ecule and one Cl atom. The crystal structure involves inter-molecular C-H⋯Cl, O-H⋯Cl and O-H⋯O hydrogen bonds.

Methyl 5-[N,N-bis-(methoxy-carbonyl-meth-yl)amino]-4-cyano-2-methoxy-carbonyl-3-thio-phene-ethan-o-ate.

In the title compound, C(16)H(18)N(2)O(8)S, derived from ranelic acid, there is a highly substituted thio-phene ring. The crystal structure involves inter-molecular C-H⋯O and C-H⋯S hydrogen bonds.

2,2'-[1-(2,4,6-Trichlorophenyl)-1H-1,2,4-triazole-3,5-diyl]diphenol.

The title compound, C(20)H(12)Cl(3)N(3)O(2), was synthesized by the reaction of 2-(2-hydroxy-phen-yl)benz[e][1,3]oxazin-4-one with 2,4,6-trichloro-phenyl-hydrazine in ethanol. The trichloro-phenyl ring is nearly perpendicular to the triazole plane [dihedral angle 80.56 (8)°], whereas the two hydroxy-phenyl rings are approximately coplanar with the triazole ring [dihedral angles of 2.79 (12) and 8.00 (14)°]. Intra-molecular O-H⋯N hydrogen bonding is observed between the hydroxy-phenyl and triazole rings.

(RS)-N-[(4-Chloro-phen-yl)(phen-yl)-meth-yl]-formamide.

The racemic title compound, C(14)H(12)ClNO, contains two mol-ecules in the asymmetric unit. The dihedral angles between the phenyl and benzene rings are 84.03 (15) and 83.92 (13)°. The crystal structure involves inter-molecular N-H⋯O, C-H⋯Cl and C-H⋯O hydrogen bonds, linking mol-ecules into layers parallel to the (100) plane.

3-Benzyl-oxypyridin-2-amine.

In the title compound, C(12)H(12)N(2)O, the dihedral angle between the planes of the pyridine and phenyl rings plane is 35.94 (12)°. In the crystal structure, centrosymmetrically related mol-ecules are linked by a pair of N-H⋯N hydrogen bonds, forming a dimer with an R(2) (2)(8) ring motif. In addition, there is an intra-molecular N-H⋯O inter-action.

Bis{µ-2-[2-(2-pyrid-yl)ethyl-imino-meth-yl]phenolato}bis-[azido-zinc(II)].

In the centrosymmetric title dinuclear zinc(II) compound, [Zn(2)(C(14)H(13)N(2)O)(2)(N(3))(2)], each Zn(II) ion has a slightly distorted trigonal bipyramidal geometry and is coordinated by two N atoms and one O atom from one Schiff base ligand, an O atom from the other Schiff base ligand, and another N atom from an azide ligand. The crystal structure involves inter-molecular C-H⋯N hydrogen bonds.

4,4,5,5-Tetra-methyl-2-(4-pyridyl)-imidazolidin-1-oxyl-3-oxide trichloroacetic acid solvate.

In the title compound, C(12)H(16)N(3)O(2)·C(2)HCl(3)O(2), the imidazolidine ring adopts a twist conformation. The crystal structure is stabilized by inter-molecular O-H⋯N hydrogen bonds.

catena-Poly[[bis-(3-benzoyl-pyridine-κN)zinc(II)]-di-µ-dicyanamido-κN:N].

The title compound, [Zn(C(2)N(3))(2)(C(12)H(9)NO)(2)](n), is a polymeric zinc(II) complex with the metal ion located on an inversion centre. The Zn(II) ion is six-coordinated by two N atoms of two 3-benzoyl-pyridine ligands and four N atoms from four dicyanamide ligands, forming a slightly distorted octa-hedral configuration. In the crystal structure, neighboring Zn atoms are linked together by double dicyanamide bridges to form a polymeric zinc(II) complex.

Aqua-bis(2-methyl-4-oxopyrido[1,2-a]pyrimidin-9-olato)zinc(II) monohydrate.

The crystal structure of the title compound, [Zn(C(9)H(7)N(2)O(2))(2)(H(2)O)]·H(2)O, involves discrete mononuclear complex mol-ecules. The special positions on the rotation twofold axis are occupied by Zn(II) and O atoms of the coordinated and uncoordinated water mol-ecules. The coordination around the Zn(II) atom can be described as transitional from trigonal-bipyramidal to square-pyramidal. The two chelating 2-methyl-4-oxopyrido[1,2-a]pyrimidin-9-olate ligands and the coordin-ated water mol-ecule form the Zn coordination. O-H⋯O hydrogen bonds between the coordinated water mol-ecule and the ligand and between the uncoordinated water mol-ecule and the ligand dominate the crystal packing.

Hepatocellular carcinoma model cell lines with two distinct migration modes.

Migration is an essential feature of metastatic cancer cells. To understand how motility is regulated in hepatocellular carcinoma, we analyzed gene expression profiles of mouse model cell lines we established from transgenic mice carrying SV40 large T antigen. A non-motile HC9 cell line was isolated from mouse liver tumors, and two additional cell lines, HCM1 and HCM4, were derived from HC9 cells. We found that both HCM1 and HCM4 cells were substantially more migratory than HC9, and that HCM1 generated tumor nodules in nude mice. In contrast to HCM4 cells that exhibited mesenchymal cell-type gene expression similar to HC9 cells, HCM1 cells appeared to have undergone a mesenchymal-amoeboidal transition. Thus, HCM1 and HCM4 cells have distinct migration and gene expression patterns, and together with HC9 cells, they can serve as model cell lines for understanding how migration is acquired and controlled in hepatocellular carcinoma.

Mortality report of malignant tumors in SheXian, Hebei Province, China, from the 1970's to the present.

BACKGROUND: Investigations into mortality from malignant tumors were initiated in the 1970's in Hebei Province, China, and especially for esophageal cancer the rates were high, Shexian county ranking in first place of the towns that were surveyed. METHODS: Since the 1970's, a register system for all causes of death has been in place. Data for the decades of the 1970's, 1980's, 1990's and 2000's century were here checked and analyzed by SPSS software. RESULT: From the decades of the 1970's onward, the mortality rates of malignant tumors/100,000 were 272.0, 260.1, 211.7 and 180.1, respectively, with significant differences over time (x2 =240.5, P<0.001). The main malignant tumors were esophageal, gastric, liver, lung and cervix cancers. The sum of their percentages of all cancer deaths were 92.1% in the 1970's, 91.6% in the 1980's, 92.1% in the 1990's and 93.9% in the 21st century. The sex ratios (male vs female) were 1.5, 1.5, 1.7 and 2.0 respectively, with an ascending trend. Mortality rates of malignant tumors increased with age, with an obvious geographic distribution. The highest mortality of malignant tumors was evident in the area where the Qingzhang and Zhuozhang rivers join. CONCLUSION: From 1970's to the beginning of the 21st century, the mortality rate of malignant tumors has shown a declining trend. The main responsible cancers are in the esophagus, stomach, liver, and lung. Through great efforts for prevention, obvious decrease for esophageal cancer and cervix cancer has been achieved, but the mortality rate for gastric cancer remains high.