Cardiac remodeling caused by transgenic overexpression of a corn Rac gene

Rac1-GTPase activation plays a key role in the development and progression of cardiac remodeling. Therefore, we engineered a transgenic mouse model by overexpressing cDNA of a constitutively active form of Zea maize Rac gene (ZmRacD) specifically in the hearts of FVB/N mice. Echocardiography and MRI analyses showed cardiac hypertrophy in old transgenic mice, as evidenced by increased left ventricular (LV) mass and LV mass-to-body weight ratio, which are associated with relative ventricular chamber dilation and systolic dysfunction. LV hypertrophy in the hearts of old transgenic mice was further confirmed by an increased heart weight-to-body weight ratio and histopathology analysis. The cardiac remodeling in old transgenic mice was coupled with increased myocardial Rac-GTPase activity (372%) and ROS production (462%). There were also increases in α(1)-integrin (224%) and β(1)-integrin (240%) expression. This led to the activation of hypertrophic signaling pathways, e.g., ERK1/2 (295%) and JNK (223%). Pravastatin treatment led to inhibition of Rac-GTPase activity and integrin signaling. Interestingly, activation of ZmRacD expression with thyroxin led to cardiac dilation and systolic dysfunction in adult transgenic mice within 2 wk. In conclusion, this is the first study to show the conservation of Rho/Rac proteins between plant and animal kingdoms in vivo. Additionally, ZmRacD is a novel transgenic model that gradually develops a cardiac phenotype with aging. Furthermore, the shift from cardiac hypertrophy to dilated hearts via thyroxin treatment will provide us with an excellent system to study the temporal changes in cardiac signaling from adaptive to maladaptive hypertrophy and heart failure.     

Mutations in c4orf26, encoding a Peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta

Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.     

Reactivity of metal chelates of sulphur containing ligands towards Lewis bases. Part III. Reaction of bis(1,2-dimethyl-and 1-phenyl-1,2-ethanediylidene)bis(S-methylhydrazinecarbodithioate)NN′SS′(−2)dizinc(II) with pyridines

The reaction of the dimeric zinc(II) chelates of the type I (R₁ = R₂ = CH₃, R₁ = H, R₂ = Ph) with pyridine, 2-methylpyridine, 3-methylpyridine and 4-methylpyridine afforded the monomeric monobase adducts. The isolated adducts were characterized by their electronic and ¹H NMR spectra, and a five coordinate square pyramidal structure was tentatively assigned for these adducts.The adduct formation reaction was followed spectrophotometrically and the reaction kinetics were studied using a stopped flow technique. From the available kinetic data, as well as the measured activated parameters (ΔH^#, ΔS^#), a mechanism for the adduct formation reaction is proposed.     

Effects of Silver Nanoparticles on Burn Wound Healing in a Mouse Model

Biological Trace Element Research - Healing of injuries caused by exposure to heat has been discussed in many studies, although a few drugs have been shown to produce satisfactory results. In this...     

Protection against cisplatin-induced nephrotoxicity by Cu(II)2(3,5-diisopropylsalicylate)4

The ability of Cu(II)(2)(3,5-diisopropylsalicylate)(4), CuDIPS, which exhibits superoxide dismutase (SOD)-like activity, to prevent cisplatin-induced nephrotoxicity was examined in rats. Rats were divided into four groups and treated as follows: (i) vehicle control; (ii) cisplatin (16 mg/kg, intraperitoneally); (iii) CuDIPS (10 mg/kg, intraperitoneally); and (iv) cisplatin plus CuDIPS. Rats were sacrificed 3 days post-treatment. Cisplatin alone resulted in significantly increased plasma creatinine and urea. Administration of 10 mg/kg CuDIPS prevented the cisplatin-induced elevation of plasma creatinine and urea and protected against kidney damage. Relative to controls, rats that received cisplatin treatment displayed a decrease of reduced glutathione (GSH) and elevated platinum and thiobarbituric acid reactive substances (TBARS) levels in the kidney. In comparison with controls, activities of antioxidant enzymes (SOD, CAT, GSH-Px and GSH-Rd) were also reduced in the kidney of rats treated with cisplatin. Administration of 10 mg/kg CuDIPS prevented cisplatin-induced alterations in renal platinum, GSH, TBARS, and antioxidant enzyme activities. This study suggests that the protection offered by CuDIPS against cisplatin-induced nephrotoxicity is partly related to maintenance of renal antioxidant systems.     

Studying the Influence of the Pyrene Intercalator TINA on the Stability of DNA i-Motifs

Certain cytosine-rich (C-rich) DNA sequences can fold into secondary structures as four-stranded i-motifs with hemiprotonated base pairs. Here we synthesized C-rich TINA-intercalating oligonucleotides by inserting a nonnucleotide pyrene moiety between two C-rich regions. The stability of their i-motif structures was studied by using UV melting temperature measurements and circular dichroism spectra at different pH values under noncrowding and crowding conditions (20% poly(ethylene glycol)). When TINA ((R)-3-((4-(1-pyrenylethynyl)benzyl)oxy) propane-1,2-diol) is inserted, the oligonucleotides could form an i-motif at a higher pH than observed for the corresponding wildtype oligonucleotide.     

Association of interleukin-2, interleukin-21 and interleukin-23 with hyperlipidemia in pediatric type 1 diabetes

Molecular Biology Reports - In type 1 diabetes mellitus (T1DM), cytokines have a central role in orchestrating multicellular relations between β-cells and immune cells. This study aims to...     

Comparison of the dynamics of the primary events of bacteriorhodopsin in its trimeric and monomeric states

In this paper, femtosecond pump-probe spectroscopy in the visible region of the spectrum has been used to examine the ultrafast dynamics of the retinal excited state in both the native trimeric state and the monomeric state of bacteriorhodopsin (bR). It is found that the excited state lifetime (probed at 490 nm) increases only slightly upon the monomerization of bR. No significant kinetic difference is observed in the recovery process of the bR ground state probed at 570 nm nor in the fluorescent state observed at 850 nm. However, an increase in the relative amplitude of the slow component of bR excited state decay is observed in the monomer, which is due to the increase in the concentration of the 13-cis retinal isomer in the ground state of the light-adapted bR monomer. Our data indicate that when the protein packing around the retinal is changed upon bR monomerization, there is only a subtle change in the retinal potential surface, which is dependent on the charge distribution and the dipoles within the retinal-binding cavity. In addition, our results show that 40% of the excited state bR molecules return to the ground state on three different time scales: one-half-picosecond component during the relaxation of the excited state and the formation of the J intermediate, a 3-ps component as the J changes to the K intermediate where retinal photoisomerization occurs, and a subnanosecond component during the photocycle.     

Non-phenolic antioxidant compounds from Buddleja asiatica

The methanol extract of the leaves of Buddleja asiatica Lour. (Loganiaceae) showed antioxidant activity toward the well known in vitro antioxidant tests such as total antioxidant capacity by the phosphomolybdenum method, free radical scavenging activity by the 1,1-diphenyl-2-picrylhydrazyl scavenging assay (DPPH assay) and hydrogen peroxide scavenging methods. Due to the high scavenging activity of the n-butanol successive fraction toward DPPH and H2O2 (SC50 = 11.99 and 18.54 microg/ml, respectively), this extract was subjected to chromatographic separation and isolation. Four non-phenolic compounds were isolated and identified on the basis of spectroscopic and chemical analyses: 1-O-beta-D-glucopyranosyl-2-methoxy-3-(2-hydroxy-triaconta-3,12-dienoate)-glycerol (1), 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)]-[beta-D-glucopyranosyl-(1-->2)]-beta-D-fucopyranosyl-olean-11,13(18)-diene-3 beta,23,28-triol (2), 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)]-beta-D-fucopyranosyl-olean-11,13(18)-diene-3,23,28-triol (3), and 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)]-[beta-D-xylopyranosyl-(1-->2)]-beta-D-glucuronopyranosyl-acid-olean-11,13(18)-diene-3 beta,23,28-triol (4). The four compounds were evaluated as antioxidant agents using the three antioxidant bioassay tests.     

Chemopreventive activity of selenocysteine prodrugs against tobacco-derived nitrosamine (NNK) induced lung tumors in the A/J mouse

Prodrugs of L-selenocysteine have potential utility in cancer chemoprevention. This study reports the efficacy of three selenazolidine-4(R)-carboxylic acids, (2-unsubstituted, 2-oxo, and 2-methyl derivatives; SCA, OSCA, and MSCA, respectively) against tobacco-related lung tumorigenesis in a mouse model. Seven days after initiation of an AIN-76A diet supplemented with sodium selenite (5 ppm Se), L-selenomethionine (3.75 ppm Se), Se-methyl-L-selenocysteine (3 ppm Se), L-selenocystine (15 ppm Se), SCA (15 ppm Se), OSCA (15 ppm Se), or MSCA (15 ppm Se), mice received 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 10 micromol, i.p.). After an additional 16 weeks on the diets, two compounds, OSCA and selenocystine, significantly reduced lung adenoma multiplicity from 7.2 tumors per mouse in the NNK group to 4.5 and 4.6 tumors per mouse, respectively. Neither selenium concentration nor glutathione peroxidase activity in either RBCs or liver served as surrogate indicators of tumor reduction. Hepatic selenium levels were significantly elevated by all selenium-containing compounds except Se-methyl-L-selenocysteine and SCA; RBC selenium levels by all except sodium selenite and MSCA. With the exception of L-selenomethionine, RBC glutathione peroxidase activity was increased along with the elevated selenium levels. Hepatic glutathione peroxidase activity was elevated by all Se-compounds except SCA. The two compounds showing significant tumor reduction (OSCA and selenocystine) were the only two compounds that showed ubiquity of changes, elevating both selenium levels and GPx activity in both liver and RBC.