[Research progress in control strategies of biological clock disorder].

Circadian clock is an internal mechanism evolved to adapt to cyclic environmental changes, especially diurnal changes. Keeping the internal clock in synchronization with the external clock is essential for health. Mismatch of the clocks due to phase shift or disruption of molecular clocks may lead to circadian disorders, including abnormal sleep-wake cycles, as well as disrupted rhythms in hormone secretion, blood pressure, heart rate, body temperature, etc. Long-term circadian disorders are risk factors for various common critical diseases such as metabolic diseases, cardiovascular diseases, and tumor. To prevent or treat the circadian disorders, scientists have conducted extensive research on the function of circadian clocks and their roles in the development of diseases, and screened hundreds of thousands of compounds to find candidates to regulate circadian rhythms. In addition, melatonin, light therapy, exercise therapy, timing and composition of food also play a certain role in relieving associated symptoms. Here, we summarized the progress of both drug- and non-drug-based approaches to prevent and treat circadian clock disorders.

[Research advances in relationship between biological clock and cardiovascular diseases].

Circadian rhythms widely exist in living organisms, and they are regulated by the biological clock. Growing evidence has shown that circadian rhythms are tightly related to the physiological function of the cardiovascular system, including blood pressure, heart rate, metabolism of cardiomyocytes, function of endothelial cells, and vasoconstriction and vasodilation. In addition, disruption of circadian rhythms has been considered as one of the important risk factors for cardiovascular diseases, such as myocardial infarction. This review summarizes the recent research advances in the relationship between circadian clock and cardiovascular diseases, hoping to improve treatment strategies for patients with cardiovascular diseases according to the theory of biological clock.

Poly[aqua-[µ-1,2-bis-(pyridin-4-yl)ethene-κ(2)N:N'][µ-5-(diphenyl-phosphino-yl)iso-phthalato-κ(3)O(1),O(1'):O(3)]nickel(II)].

In the title compound, [Ni(C(20)H(13)O(5)P)(C(12)H(10)N(2))(H(2)O)](n), the Ni(II) cation is coordinated by three O atoms from two 5-(diphenyl-phosphino-yl)isophthalate anions, two N atoms from two 1,2-bis-(pyridin-4-yl)ethene ligands and one water mol-ecule in a distorted octa-hedral geometry. Both 1,2-bis-(pyridin-4-yl)ethene and 5-(diphenyl-phosphino-yl)iso-phthal-ate bridge the Ni(II) cations to form polymeric layers parallel to (001). In the crystal, O-H⋯O hydrogen bonding links layers into a three-dimensional supra-molecular structure.

Ethane-1,2-diaminium bis-(4-carb-oxy-2-propyl-1H-imidazole-5-carb-oxy-ate) monohydrate.

In the title hydrated molecular salt, C(2)H(10)N(2) (2+)·2C(8)H(9)N(2)O(4) (-)·H(2)O, an intra-molecular O-H⋯O hydrogen bond occurs in the anion, forming an S(7) ring. The -CO(2) and -CO(2)H groups make dihedral angles of 3.2 (2) and 2.0 (3)°, respectively, with the five-membered ring. In the crystal, N-H⋯O, N-H⋯N and O-H⋯O hydrogen bonds lead to the formation of a three-dimensional supra-molecular architecture. The methyl group in the anion is disordered over two sets of sites in a 0.716 (9):0.284 (9) ratio. The ethylenediamine cation is generated by symmetry and the water molecule lies on a twofold axis.

Bis{N(2),N(6)-bis-[(pyridin-3-yl)meth-yl]pyridine-2,6-dicarboxamide-κN}bis-(methanol-κO)bis-(thio-cyanato-κN)cobalt(II).

In the title compound, [Co(NCS)(2)(C(19)H(17)N(5)O(2))(2)(CH(3)OH)(2)], the Co(II) atom lies on an inversion center and is coordinated by two isothio-cyanate N atoms, two O atoms of methanol mol-ecules and two pyridine N atoms in a slightly distorted octa-hedral environment. Inter-molecular O-H⋯O and N-H⋯N hydrogen bonds join the complex mol-ecules into layers parallel to the bc plane.

Penta-aqua-(5-carb-oxy-pyridine-2-carboxyl-ato-κN,O)(pyridine-2,5-dicarboxyl-ato-κN,O)cerium(III) tetra-hydrate.

In the title compound, [Ce(C(7)H(3)NO(4))(C(7)H(4)NO(4))(H(2)O)(5)]·4H(2)O, the Ce(3+) ion is nine-coordinated by two O atoms and two N atoms from one single and from one double deprotonated pyridine-2,5-dicarboxyl-ate ligand and five water mol-ecules in a distorted monocapped square-anti-prismatic geometry. In the crystal, extensive O-H⋯O hydrogen-bonding inter-actions result in a three-dimensional supra-molecular architecture.

Tetra-aqua-bis-(2-{[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]sulfan-yl}acetato)-cobalt(II) monohydrate.

In the title compound, [Co(C(9)H(6)N(3)O(3)S)(2)(H(2)O)(4)]·H(2)O, the two 2-{[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]sulfan-yl}acetate ligands are monodentate. One coordinates the metal atom via the pyridyl N atom whereas the other coordinates via the carboxyl-ate O atom. The Co(II) atom adopts a slightly distorted octa-hedral coordination geometry with four O atoms of the coordinated water mol-ecules located in the equatorial plane and the N and O atoms of the two POA ligands in axial positions. In the crystal, the components are connected through O-H⋯O and O-H⋯N hydrogen bonds into a three-dimensional framework.

Poly[(5,5'-dimethyl-2,2'-bipyridine-κN,N')(µ(3)-5-hy-droxy-isophthalato-κO:O,O:O)cadmium].

In the title compound, [Cd(C(8)H(4)O(5))(C(12)H(12)N(2))], the Cd(II) cation is coordinated by three 5-hy-droxy-isophthalate anions and one 5,5'-bimethyl-2,2'-bipyridine ligand in a distorted CdO(4)N(2) octa-hedral geometry. The 5-hy-droxy-isophthalate anions bridge the Cd cations, forming a two-dimensional polymeric complex parallel to (100). In the complex, the hy-droxy group is linked to the uncoordinated carb-oxy-O atom via an O-H⋯O hydrogen bond. Weak C-H⋯O hydrogen bonds are also present in the crystal structure. One of the methyl groups is disordered over two positions in a 0.536 (11):0.464 (11) ratio.

Poly[bis[µ-1,3-bis-(imidazol-1-ylmeth-yl)benzene-κN:N]bis-(nitrato-κO)cadmium].

A novel metal-organic framework based on 1,3-bis-(imidazol-1-ylmeth-yl)benzene (1,3-bimb), [Cd(NO(3))(2)(C(14)H(14)N(4))(2)](n), has been synthesized hydro-thermally. The structure exhibits a two-dimensional metal-organic (4,4)-net composed of Cd(II) atoms and bimb ligands, and such layers are further joined through inter-layer C-H⋯O hydrogen bonds to generate a three-dimensional supra-molecular structure.

Enhanced pressor response to acute Ang II infusion in mice lacking membrane-associated prostaglandin E2 synthase-1.

AIM: To examine the contribution of vascular membrane-associated prostaglandin E2 synthase-1 (mPGES-1) to acute blood pressure homeostasis. METHODS: Angiotensin II (AngII, 75 pmol·kg⁻¹·min⁻¹) was continuously infused via the jugular vein into wild-type and mPGES-1(-/-) mice for 30 min, and blood pressure was measured by carotid arterial catheterization. RT-PCR and immunohistochemistry were performed to detect the expression and localization of mPGES-1 in the mouse arterial vessels. Mesenteric arteries were dissected from mice of both genotypes to study vessel tension and measure vascular PGE2 levels. RESULTS: Wild-type and mPGES-1(-/-) mice showed similar blood pressure levels at baseline, and the acute intravenous infusion of AngII caused a greater increase in mean arterial pressure in the mPGES-1(-/-) group, with a similar diuretic and natriuretic response in both groups. mPGES-1 was constitutively expressed in the aortic and mesenteric arteries and vascular smooth muscle cells of wild-type mice. Strong staining was detected in the smooth muscle layer of arterial vessels. Ex vivo treatment of mesenteric arteries with AngII produced more vasodilatory PGE2 in wild-type than in mPGES-1(-/-) mice. In vitro tension assays further revealed that the mesenteric arteries of mPGES-1(-/-) mice exhibited a greater vasopressor response to AngII than those arteries of wild-type mice. CONCLUSION: Vascular mPGES-1 acts as an important tonic vasodilator, contributing to acute blood pressure regulation.

[High glucose downregulates the expression of podocalyxin protein in glomerular podocytes of mice].

OBJECTIVE: To examine the expression of podocalyxin protein in glomerular podocytes by long-term high glucose exposure in vitro and in vivo. METHODS: Immunohistochemical staining and computer image analysis were applied to detect the expression of podocalyxin protein in glomeruli from db/db mice and Wt mice. The effects of high glucose on the expression of podocalyxin protein were analyzed by Western blotting. The activation of MAPKS signaling pathway (ERK, p38 and JNK) by high glucose was also examined. RESULTS: The expressions of podocalyxin protein in db/db mice were obviously less than that in Wt mice [(0.18+/-0.07) vs (0.25+/-0.05),P<0.05] assessed by immunostaining and semiquantitative analysis. Basal levels of podocalyxin protein were observed in cultured mouse podocytes. The level of podocalyxin protein declined at each time point by high glucose incubation, reached the lowest level on the 6th day (5.5% of control group, P<0.01), but no significant changes were observed in normal glucose and mannitol glucose incubation groups. High glucose medium induced phosphorylation of ERK1/2 as early as 30 minutes, reached the peak at hour 6; maintained the activation from hour 12 to 24, and declined to the basal level at hour 48. However, activation of ERK1/2 was not detected in normal glucose and mannitol glucose groups. Blockade of activation of ERK1/2 with PD98059, a specific ERK1/2 activation inhibitor, attenuated the high glucose-induced expression of podocalyxin protein on the 6th day. CONCLUSION: High ambient glucose decreases the protein level of podocalyxin by podocyte in vitro and in vivo, and the decrease in podocalyxin protein is ERK1/2jdependent in cultured podocytes.

[Liver X receptors mediate cholesterol efflux in mouse glomerular mesangial cells].

OBJECTIVE: To examine the role of liver X receptors (LXRs) in lipid metabolism in cultured mouse mesangial cells. METHODS: To determine whether LXRalpha and LXRbeta are expressed in the kidney, RT-PCR and western blot assay were utilized. Cultured mesangial cells were treated with either vehicle or LXR agonist TO901317(10 micromol/L) for 24 hours. Real-time PCR analysis was used to detect ABCA1 and ABCG1 expressions. Cells were also transfected with a human ABCA1 promoter driven luciferase reporter plasmid and then stimulated with or without TO901317 for 24 hours. In order to determine the effect of TO901317 on protein expression of ABCA1, LXRalpha adenovirus was used to overexpress LXRalpha in the cultured cells. Finally, [3H] cholesterol efflux assay was performed to evaluate the efflux of cholesterol upon TO901317 stimulation. RESULTS: Both LXRalpha and LXRbeta were expressed in the kidney, freshly isolated glomeruli and mesangial cells. After treatment with TO901317, both ABCA1 and ABCG1 expressions were induced. Moreover, ABCA1 protein level was increased after the cells were simultaneously treated with LXRalpha-adenovirus and TO901317. The cholesterol efflux was also significantly enhanced after TO901317 treatment. CONCLUSION: LXRalpha and LXRbeta were functionally expressed in mouse mesangial cells. Activation of LXRs enhanced cholesterol efflux possibly through upregulating ABCA1 and ABCG1 expressions in mesangial cells. Therefore, LXR agonist might ameliorate lipid accumulation and reduce related cell injury in mesangial cells.