Identification of hub genes and molecular pathways in human T-lymphotropic virus type 1 associated diseases using protein-protein interactions networks.

Background and Objectives: Human T-lymphotropic virus type 1 (HTLV-1) is the cause of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The present study aims to analyze gene expression patterns in ATL and HAM/TSP. Materials and Methods: Microarray gene expression profiling of T-lymphocytes from HTLV-1 associated disease and healthy control were obtained from Gene Expression Omnibus (GEO). Several bioinformatics tools were used to identify differentially expressed genes (DEGs). Among the generated DEGs, we constructed protein-protein interaction (PPI) between HAM/TSM and ATL in comparison to asymptomatic carriers (ACs). Subsequently, gene ontology (GO) and topological analysis were performed. Results: We found that the majority of DEGs in ATL and HAM/TSP were importantly implicated in immune response categories. The nodes and edges number of normal-AC, AC-ATL and ATL-HAM/TSP PPIs were 168 and 145, 116 and 97, and 275 and 327, respectively. Based on the topological analyses of protein-protein interaction networks, APP (Amyloid Beta Precursor Protein) was detected as a critical player in progression of HTLV-1 disease. Conclusion: Dysregulation of immune response associated transcripts play a critical role in HTLV-1 disease progression. Immune response associated genes may be biomarker for prognosis in cancer development and therapeutic targets.

Viral infection and atherosclerosis.

Several risk factors have been described for the pathogenesis of atherosclerosis. Infectious diseases are suggested to be a causative factor, and some viruses have been studied for their relation with atherosclerotic diseases. Studies report two hypotheses, direct and indirect effects, for the role of viral infections in atherogenesis. Viruses are able to initiate atherosclerosis by two different pathways. They can exert their direct effects on atherogenesis by infecting vascular cells and then inducing inflammation in the endothelium and smooth muscle cells. Alternatively, they can also apply indirect effects by infecting non-vascular cells and inducing systemic inflammation. In this review, we consider the available data about the effects and correlations of DNA and RNA viruses on atherosclerosis.

QSAR Study of 17ß-HSD3 Inhibitors by Genetic Algorithm-Support Vector Machine as a Target Receptor for the Treatment of Prostate Cancer.

The 17ß-HSD3 enzyme plays a key role in treatment of prostate cancer and small inhibitors can be used to efficiently target it. In the present study, the multiple linear regression (MLR), and support vector machine (SVM) methods were used to interpret the chemical structural functionality against the inhibition activity of some 17ß-HSD3inhibitors. Chemical structural information were described through various types of molecular descriptors and genetic algorithm (GA) was applied to decrease the complexity of inhibition pathway to a few relevant molecular descriptors. Non-linear method (GA-SVM) showed to be better than the linear (GA-MLR) method in terms of the internal and the external prediction accuracy. The SVM model, with high statistical significance (R2train = 0.938; R2test = 0.870), was found to be useful for estimating the inhibition activity of 17ß-HSD3 inhibitors. The models were validated rigorously through leave-one-out cross-validation and several compounds as external test set. Furthermore, the external predictive power of the proposed model was examined by considering modified R2 and concordance correlation coefficient values, Golbraikh and Tropsha acceptable model criteria's, and an extra evaluation set from an external data set. Applicability domain of the linear model was carefully defined using Williams plot. Moreover, Euclidean based applicability domain was applied to define the chemical structural diversity of the evaluation set and training set.

Preconcentration and determination of ceftazidime in real samples using dispersive liquid-liquid microextraction and high-performance liquid chromatography with the aid of experimental design.

A rapid and simple method for the extraction and preconcentration of ceftazidime in aqueous samples has been developed using dispersive liquid-liquid microextraction followed by high-performance liquid chromatography analysis. The extraction parameters, such as the volume of extraction solvent and disperser solvent, salt effect, sample volume, centrifuge rate, centrifuge time, extraction time, and temperature in the dispersive liquid-liquid microextraction process, were studied and optimized with the experimental design methods. Firstly, for the preliminary screening of the parameters the taguchi design was used and then, the fractional factorial design was used for significant factors optimization. At the optimum conditions, the calibration curves for ceftazidime indicated good linearity over the range of 0.001-10 µg/mL with correlation coefficients higher than the 0.98, and the limits of detection were 0.13 and 0.17 ng/mL, for water and urine samples, respectively. The proposed method successfully employed to determine ceftazidime in water and urine samples and good agreement between the experimental data and predictive values has been achieved.

3D-QSAR analysis of MCD inhibitors by CoMFA and CoMSIA.

Three-dimensional quantitative structure-activity relationship was developed for the series of compounds as malonyl-CoA decarboxylase antagonists (MCD) using the CoMFA and CoMSIA methods. The statistical parameters for CoMFA (q(2)=0.558, r(2)=0.841) and CoMSIA (q(2)= 0.615, r(2) = 0.870) models were derived based on 38 compounds as training set in the basis of the selected alignment. The external predictive abilities of the built models were evaluated by using the test set of nine compounds. From obtained results, the CoMSIA method was found to have highly predictive capability in comparison with CoMFA method. Based on the given results by CoMSIA and CoMFA contour maps, some features that can enhance the activity of compounds as MCD antagonists were introduced and used to design new compounds with better inhibition activity.

Dichlorido(6,6'-dimethyl-2,2'-bipyridine-κN,N')zinc(II).

In the title compound, [ZnCl(2)(C(12)H(12)N(2))], the complete mol-ecule is generated by crystallographic mirror symmetry, with the Zn atom and both chloride ions lying on the reflecting plane, yielding a distorted ZnN(2)Cl(2) tetra-hedral coordination for the metal ion. In the crystal, there are π-π contacts between the pyridine rings [centroid-centroid distance = 3.7857 (17) Å].

Dibromido(6,6'-dimethyl-2,2'-bipyridine-κN,N')zinc(II).

In the title compound, [ZnBr(2)(C(12)H(12)N(2))], the Zn(II) atom is four-coordinated in a distorted tetra-hedral arrangement by an N,N'-bidentate 6,6'-dimethyl-2,2'-bipyridine ligand and two bromide ions. In the crystal, there are aromatic π-π contacts between the pyridine rings [centroid-centroid distances = 3.818 (3) and 3.728 (4) Å].

Dichloridobis(phenanthridine-κN)zinc(II).

In the mol-ecule of the title compound, [ZnCl(2)(C(13)H(9)N)(2)], the Zn(II) atom is four-coordinated in a distorted tetra-hedral configuration by two N atoms from two phenanthridine ligands and by two terminal Cl atoms. The dihedral angle between the planes of the phenanthridine ring systems is 69.92 (3)°. An intra-molecular C-H⋯Cl inter-action results in the formation of a planar five-membered ring, which is oriented at a dihedral angle of 8.32 (3)° with respect to the adjacent phenanthridine ring system. In the crystal structure, π-π contacts between the phenanthridine systems [centroid-centroid distances = 3.839 (2), 3.617 (1) and 3.682 (1) Å] may stabilize the structure. Two weak C-H⋯π inter-actions are also found.

5,5'-Dimethyl-2,2'-bipyridine.

The asymmetric unit of the title compound, C(12)H(12)N(2), contains two half-mol-ecules related by an inversion center, the planes of their pyridine rings being oriented at a dihedral angle of 69.62 (4)°. In the crystal structure, a π-π contact between the pyridine rings [centroid-centroid distance = 3.895 (3) Å] may stabilize the structure. A weak C-H⋯π inter-action is also found.

Trichlorido(5,5'-dimethyl-2,2'-bipyridine-κN,N')(methanol-κO)indium(III).

In the mol-ecule of the title compound, [InCl(3)(C(12)H(12)N(2))(CH(4)O)], the In(III) atom is six-coordinated in a distorted octa-hedral configuration by two N atoms from the chelating 5,5'-dimethyl-2,2'-bipyridine ligand, one O atom from a methanol molecule and three Cl atoms. In the crystal structure, inter-molecular O-H⋯Cl hydrogen bonds link the mol-ecules into chains parallel to [001].

Di-µ-bromido-bis-[bromido(4,4'-dimethyl-2,2'-bipyridine-κN,N')mercury(II)].

The asymmetric unit of the title compound, [Hg(2)Br(4)(C(12)H(12)N(2))(2)], contains one half-mol-ecule. The Hg(II) atom is five-coordinated in a trigonal-bipyramidal configuration by two N atoms from the chelating 4,4'-dimethyl-2,2'-bipyridine ligand, two bridging Br and one terminal Br atom, leading to a centrosymmetric dimeric mol-ecule. There is a π-π contact between the pyridine rings [centroid-to-centroid distance = 3.756 (5) Å].

Dichlorido(6-methyl-2,2'-bipyridine-κN,N')mercury(II).

In the mol-ecule of the title compound, [HgCl(2)(C(11)H(10)N(2))], the Hg(II) atom is four-coordinated in a distorted tetra-hedral configuration by two N atoms from a 6-methyl-2,2'-bipyridine ligand and two Cl atoms. There is a π-π contact between the pyridine rings [centroid-centroid distance = 3.9758 (5) Å].

Dibromido(di-2-pyridylamine-κN,N')mercury(II).

In the mol-ecule of the title compound, [HgBr(2)(C(10)H(9)N(3))], the Hg(II) atom is four-coordinated in a distorted tetra-hedral configuration by two N atoms from the chelating di-2-pyridylamine ligand and by two Br atoms. In the crystal structure, inter-molecular N-H⋯Br hydrogen bonds link the mol-ecules into centrosymmetric dimers. There are π-π contacts between the pyridine rings [centroid-centroid distances = 3.9662 (5) and 3.9321 (4) Å]. There also exists a C-H⋯π contact between the pyridine CH group and a pyridine ring.

Dichlorido(6-methyl-2,2'-bipyridine-κN,N')zinc(II).

In the mol-ecule of the title compound, [ZnCl(2)(C(11)H(10)N(2))], the Zn(II) atom is four-coordinated in a distorted tetra-hedral configuration by two N atoms from the 6-methyl-2,2'-bipyridine ligand and by two Cl atoms. There are π-π contacts between the pyridine ring and the five-membered ring, and also between the pyridine rings, [centroid-centroid distances = 3.685 (3) and 3.757 (3) Å, respectively].

Bis(2,4,6-trimethyl-pyridinium) hexa-chloridoplatinate(IV).

The asymmetric unit of the title compound, (C(8)H(12)N)(2)[PtCl(6)], contains one independent protonated 2,4,6-trimethyl-pyridinium cation and one half of a centrosymmetric [PtCl(6)](2-) anion. The Pt ion has an almost ideal octa-hedral coordination. In the crystal structure, intra-molecular N-H⋯Cl and inter-molecular C-H⋯Cl hydrogen bonds result in the formation of a supra-molecular structure.

(5,5'-Dimethyl-2,2'-bipyridine-κN,N')diiodidomercury(II).

In the mol-ecule of the title compound, [HgI(2)(C(12)H(12)N(2))], the Hg(II) atom is four-coordinated in a distorted tetra-hedral configuration by two N atoms from 5,5'-dimethyl-2,2'-bipyridine and two I atoms. There is a π-π contact between pyridine rings of adjacent molecules [centroid-centroid distance = 3.723 (5) Å].

µ-2,3,5,6-Tetra-2-pyridylpyrazine-κN,N,N:κN,N,N-bis-[(methanol-κO)(nitrato-κO,O')(nitrato-κO)cadmium(II)].

The title complex, [Cd(2)(NO(3))(4)(C(24)H(16)N(6))(CH(4)O)(2)], displays a centrosymmetric dinuclear structure, in which the 2,3,5,6-tetra-2-pyridinylpyrazine (tppz) ligand links two Cd ions separated by 7.323 (4) Å. Each Cd(II) center is seven-coordinated by three N-atom donors of tppz in one plane, by two O atoms nearly normal to this plane, and by two O atoms 0.393 (3) and 0.488 (3) Šfrom that plane. The two Cd(II) ions are above and below the plane of the pyrazine ring of the tppz ligand, oriented with respect to the pyridine rings at dihedral angles of 38.01 (3) and 31.90 (3)°. The dihedral angle between the two pyridine rings is 41.11 (3)°. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules.