Search

In our bodies, a slight pH change causes remarkable activation or serious damage in the biological processes and continuously keeps biological homeostasis. Detection of such a slight pH change has been a constant demand in searching for unusual biological events. In this paper, we demonstrate a novel pH sensory system that has been achieved through a combination of charge neutralization by a slight pH change with aggregation-induced emission (AIE). We selected a cyano-functionalized oligo(phenylene-vinylene) (cyanoOPV) backbone for AIE and introduced ammonium-tethered boronic acid groups as a pH-dependent function. The self-assembling of these dyes ( OPV-Cn) was readily achieved by pH-dependent charge neutralization at the neutral pH region. This sensory system showed unusually sensitive pH responsiveness in a narrow pH range. Moreover, this pH change was observed in a biologically important neutral pH region. We therefore believe that this system is broadly applicable to detect the slight pH change occurring in the biological events. [ABSTRACT FROM AUTHOR]

Three kinds of crystals (crystals, α , β , and γ ) of 2:2 cyclic cobalt complexes formulating as [Co(Br-hfpip) 2 ( D2py 2 )] 2 X: X = 2CH 2 Cl 2 ( 1d α ), 4CH 2 Cl 2 ( 1d β ), and 4CH 2 Cl 2 ·4EtOH ( 1d γ ) and Br-hfpip = 1,1,1,5,5,5-hexafluoro-4-(4-bromophenylimino)-2-pentanonate, were obtained and were determined to be polymorphous by X-ray crystallography, having the space groups of P 1 ¯ for 1d α and 1d β , and P 2 1 / n for 1d γ . In three polymorphs, the local coordination structures of cobalt complex units in the molecule were the same; compressed octahedral. The molecular structure for 1d α was different from those for 1d β and 1d γ . The dihedral angles between the X – Y plane and the pyridine ring were 43° and 44° for 1d α and 70–80° for 1d β and 1d γ . In the crystal packings, 1d α had a short contact between the bromo substituent in hfpip ligand and the carbon at the β position of the pyridine ring in D2py 2 , while 1d β and 1d γ had no short contact between the magnetically significant atoms. The powder X-ray diffraction (PXRD) patterns for the crushed samples of three polymorphs indicated that the crystal structures were changed by loosing crystal solvent and 1d α and 1d β were microcrystals ( 1d α ′ and 1d β ′ ), while 1d γ became amorphous ( 1d γ ′ ). In dc and ac magnetic measurements after irradiation of crushed samples ( 1d α ′ , 1d β ′ , and 1d γ ′ ), the photoproducts, 1c α ′ , 1c β ′ , and 1c γ ′ exhibited slow magnetic relaxation and magnetic hysteresis. 1c α ′ showed a single-molecule magnet (SMM) behavior with the effective activation barrier, U eff / k B = 98 K and coercive force, H c = 2.9 kOe at 1.9 K affected by the intermolecular antiferromagnetic interaction. 1c β ′ showed the magnetic behavior with U eff / k B = 134 K and H c = 13 kOe at 1.9 K typical of heterospin SMM. In 1c γ ′ , weak χ mol ″ signals with frequency dependency and the temperature dependent hysteresis loop; H c = 1.1 kOe at 1.9 K, were observed. [ABSTRACT FROM AUTHOR]

Abstract: One-to-one mixtures of Co(hfpip and hfnip)2; hfpip=1,1,1,5,5,5-hexafluoro-4-(phenylimino)-2-pentanonato and hfnip=1,1,1,5,5,5-hexafluoro-4-(1-naphthylimino)-2-pentanonato, and 1,3-phenylenebis(4-pyridyldiazomethane), D2py2 , gave diazo-cobalt complexes, 1 and 2, respectively, formulated by [Co(hfpip and hfnip)2(D2py2)] n . Complex 2 was obtained as a single crystal and was found to have a zig-zag chain structure in the cis coordination of pyridines in D2py2 to the cobalt ions by X-ray crystallography. After irradiation of microcrystalline samples of 1 and 2, the generated carbene-cobalt complexes, 1c and 2c, showed magnetic properties due to ferromagnetic chains. Those complexes exhibited slow magnetic relaxations with U eff/k B =109 and 129K and temperature-dependent hysteresis loops with H c =11 and 9kOe at 1.9K for 1c and 2c, respectively. [Copyright &y& Elsevier]

Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the treatment of fibrocystic liver disease in ARPKD patients. [ABSTRACT FROM AUTHOR]

Hold and connect! Inclusion of a bridging ligand into cyclodextrin (CD), followed by the addition of TbIII leads to a polyrotaxane‐type metallosupramolecular polymer (see figure, L=4,4′‐biphenyldicarboxylic acid). This polymer can recognize chirality and differentiate enantiomers by fluorescence and circular dichroism spectral changes. [ABSTRACT FROM AUTHOR]

Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γ agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoylcoenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism. [ABSTRACT FROM AUTHOR]

Abstract: The mixtures of Co(X-hfpip)2; X=I and H, and bisdiazo-dipyridine ligands, D2py2 (TBA), in 1:1 ratios gave the discrete cobalt complexes, 1 and 2, respectively. The molecular structures for 1 and 2 revealed by X-ray crystallography were cyclic 2:2 cobalt complexes formulated as [(Co(X-hfpip) 2 ) 2 (D2py2 (TBA)) 2 ], in which the cobalt units were compressed octahedra. After irradiation of the microcrystalline samples, the resulting Co–carbene complexes, 1c and 2c, showed SMM behaviors exhibiting slow magnetic relaxations. In dc and ac magnetic susceptibility experiments, the activation barrier, U eff, for reorientation of the magnetic moment were estimated to be 139 and 135K for 1c and 2c, respectively, and the hysteresis loops of the magnetization (the coercive force, H c, and 26 and 15kOe at 1.9K for 1c and 2c, respectively) were observed. In addition, the values of the quantum tunneling time, τ Q, were determined to be 1.1×105 and 5.4×105 s (t 1/2 =21 and 104h) for 1c and 2c, respectively, below 2.5K. [Copyright &y& Elsevier]

In autosomal recessive polycystic kidney disease (ARPKD), progressive enlargement of fluid-filled cysts is due to aberrant proliferation of tubule epithelial cells and transepithelial fluid secretion leading to extensive nephron loss and interstitial fibrosis. Congenital hepatic fibrosis associated with biliary cysts/dilatations is the most common extrarenal manifestation in ARPKD and can lead to massive liver enlargement. Peroxisome proliferator-activated receptor γ (PPAR-γ), a member of the ligand-dependent nuclear receptor superfamily, is expressed in a variety of tissues, including the kidneys and liver, and plays important roles in cell proliferation, fibrosis, and inflammation. In the current study, we determined that pioglitazone (PIO), a PPAR-γ agonist, decreases polycystic kidney and liver disease progression in the polycystic kidney rat, an orthologous model of human ARPKD. Daily treatment with 10 mg/kg PIO for 16 wk decreased kidney weight (% of body weight), renal cystic area, serum urea nitrogen, and the number of Ki67-, pERK1/2-, and pS6-positive cells in the kidney. There was also a decrease in liver weight (% of body weight), liver cystic area, fibrotic index, and the number of Ki67-, pERK1/2-, pERK5-, and TGF-β-positive cells in the liver. Taken together, these data suggest that PIO inhibits the progression of polycystic kidney and liver disease in a model of human ARPKD by inhibiting cell proliferation and fibrosis. These findings suggest that PPAR-γ agonists may have therapeutic value in the treatment of the renal and hepatic manifestations of ARPKD. [ABSTRACT FROM AUTHOR]

An original reduced elementary reaction scheme for a gas mixture including the components of natural gas and gas oil has been constructed. Also, the combustion process in a supercharged dual-fuel engine, in which a mixture of natural gas and air was fed from an intake port and a small amount of gas oil was injected as an ignition source, has been computed three-dimensionally with consideration for chemical kinetics and with the authors' GTT code linked to CHEMKIN-II subroutines. The validity of the proposed chemical kinetic model has been confirmed by comparing the calculated results with experimental results. [ABSTRACT FROM AUTHOR]

The vector control method is widely used for induction motor drives. In these applications, a rotational transducer such as a shaft encoder is used. A rotational transducer, however, cannot be mounted in some cases, such as motor drives in a hostile environment or high-speed motor drives. Several sensorless vector-controlled induction machine drive methods have been proposed. These methods have the disadvantage that rotor resistance variation causes errors in the estimation of the motor speed. It is difficult to estimate the motor speed and the rotor resistance simultaneously, because the equivalent rotor resistance is the ratio of the rotor resistance to the slip at steady state. Therefore, we have proposed a method of simultaneously estimating the motor speed and the rotor resistance of an induction motor by superimposing ac components on the field current command. This paper presents a modified method of the rotor resistance adaptation. The validity of the proposed method is verified by experiments. © 1998 Scripta Technica, Electr Eng Jpn, 125(2): 65–72, 1998 [ABSTRACT FROM AUTHOR]

The article examines the crystal structure of the dinuclear cobalt (II) complex composed of didiazo-dipyridine ligand D2py2(TBA) and cobalt complex Co(hfpip)2. Based on the study, researchers suggest that the magnetic interactions between the anisotropic cobalt ion and the carbenes generated by photolysis produced the observed the single-molecule magnets (SMMs) character. They observe the activation barrier, Ueff, in the 1:4 complex of the cobalt.

The newly developed oligophenylenevinylene (OPV)-based fluorescent (FL) chiral chemosensor (OPV-Me) for the representative enantiomeric guest, 1,2-cyclohexanedicarboxylic acid (1,2-CHDA: RR- and SS-form) showed the high chiral discrimination ability, resulting in the different aggregation modes of OPV-Me self-assembly: RR-CHDA directed the fibrous supramolecular aggregate, whereas SS-CHDA directed the finite aggregate. The consequent FL intensity toward RR-CHDA was up to 30 times larger than that toward SS-CHDA. Accordingly, highly enantioselective recognition was achieved. Application to the chirality sensing was also possible: OPV-Me exhibited a linear relationship between the FL intensity and the enantiomeric excess through the morphological development of stereocomplex aggregates. These results clearly show that the chiral recognition ability is manifested by the amplification cascade of the chirality difference through self-assembly. [ABSTRACT FROM AUTHOR]

The newly developed oligophenylenevinylene (OPV)-based fluorescent (FL) chiral chemosensor (OPV-Me) for the representative enantiomeric guest, 1,2-cyclohexanedicarboxylic acid (1,2-CHDA: RR- and SS-form) showed the high chiral discrimination ability, resulting in the different aggregation modes of OPV-Me self-assembly: RR-CHDA directed the fibrous supramolecular aggregate, whereas SS-CHDA directed the finite aggregate. The consequent FL intensity toward RR-CHDA was up to 30 times larger than that toward SS-CHDA. Accordingly, highly enantioselective recognition was achieved. Application to the chirality sensing was also possible: OPV-Me exhibited a linear relationship between the FL intensity and the enantiomeric excess through the morphological development of stereocomplex aggregates. These results clearly show that the chiral recognition ability is manifested by the amplification cascade of the chirality difference through self-assembly. [ABSTRACT FROM AUTHOR]

The control over supramolecular interactions and obtaining information beyond the molecular scale is an extended challenge. The intriguing self-assembly of a perylene-3,4,9,10-tetracarboxylic acid diimide (PDI)-based novel bolaamphiphilic probe is experienced within an artificial environment that is restrained by using supramolecular crystallization and molecular recognition. The bolaamphiphile with a hydrophilic [18]-azacrown ether ring produced nanoaggregates due to differing solubilities in organic and aqueous media. A structural evolution was observed in the presence of alkali metal ions as guests. The metal complexes form a pseudo-cationic structure, which is further involved in an ionic self-assembly with biomolecules, thus resulting new spectroscopic information on the dye self-assembly. The overarching aim of this study is to emphasize the importance of the concept of supramolecular adaptability, which has been used to establish an environment-friendly behavior based on noncovalent forces, thus leading to the evolution of new assembly structures and photophysical properties. [ABSTRACT FROM AUTHOR]

Oligophenylenevinylene (OPV)-based fluorescent (FL) chemosensors exhibiting linear FL responses toward polyanions were designed. Their application to FL sensing of glycosaminoglycans (heparin: HEP, chondroitin 4-sulfate: ChS, and hyaluronic acid: HA) revealed that the charge density encoded as the unit structure directs the mode of OPV self-assembly: H-type aggregate for HEP with 16-times FL increase and J-type aggregate for HA with 93-times FL increase, thus unexpectedly achieving the preferential selectivity for HA in contrast to the conventional HEP selective systems. We have found that the integral magnitude of three factors consisting of binding mechanism, self-assembly, and FL response can amplify the structural information on the target input into the characteristic FL output. This emergent property has been used for a novel molecular recognition system that realizes unconventional FL sensing of HA, potentially applicable to the clinical diagnosis of cancer-related diseases. [ABSTRACT FROM AUTHOR]

Oligophenylenevinylene (OPV)-based fluorescent (FL) chemosensors exhibiting linear FL responses toward polyanions were designed. Their application to FL sensing of glycosaminoglycans (heparin: HEP, chondroitin 4-sulfate: ChS, and hyaluronic acid: HA) revealed that the charge density encoded as the unit structure directs the mode of OPV self-assembly: H-type aggregate for HEP with 16-times FL increase and J-type aggregate for HA with 93-times FL increase, thus unexpectedly achieving the preferential selectivity for HA in contrast to the conventional HEP selective systems. We have found that the integral magnitude of three factors consisting of binding mechanism, self-assembly, and FL response can amplify the structural information on the target input into the characteristic FL output. This emergent property has been used for a novel molecular recognition system that realizes unconventional FL sensing of HA, potentially applicable to the clinical diagnosis of cancer-related diseases. [ABSTRACT FROM AUTHOR]

Although self-assembly has realized the spontaneous formation of nanoarchitectures, the nanoscopic expression of chemical structural information at the molecular level can alternatively be regarded as a tool to translate molecular structural information with high precision. We have found that a newly developed guanidinium-tethered oligophenyle-nevinylene exhibits characteristic fluorescence (FL) responses toward l- and meso-tartarate, wherein the different self-assembly modes, termed J- or H-type aggregation, are directed according to the molecular information encoded as the chemical structure. This morphological difference originates from the geometric anti versus gauche conformational difference between l- and meso-tartarate. A similar morphological difference can be reproduced with the geometric C=C bond difference between fumarate and maleate. In the present system, the dicarboxylate structural information is embodied in the inherent threshold concentration of the FL response, the signal-to-noise ratio, and the maximum FL wavelength. These results indicate that self-assembly is meticulous enough to sense subtle differences in molecular information and thus demonstrate the potential ability of self-assembly for the expression of a FL sensory system. [ABSTRACT FROM AUTHOR]

A novel tetraphenylethene-based fluorescence (FL) chemosensor exhibits nonlinear turn-on FL switching though cooperative binding of L-tartarate, where its convergent binding to form cyclic substructures is responsible for the FL increase. This binding scheme achieves selective detection of dicarboxylates over monocarboxylates, thus is potentially applicable to the preliminary screening for metabolic disorders. [ABSTRACT FROM AUTHOR]

We demonstrate a new method for the preparation of silver nanoparticles (AgNPs) utilising dye-sensitised photo-reduction on triple-stranded β-1,3-glucans. Reflecting the chiral helical structure of these polysaccharides, the chiral plasmonic AgNPs were yielded when hydrophobic dyes strongly interacting with the helical β-1,3-glucan main-chain were used. This system offers a new strategy to create chiral plasmonic AgNPs and a new idea to utilise helix-forming polysaccharides as a chiral template. [ABSTRACT FROM AUTHOR]

Emissive push–pull‐type bisnaphthyridylamine derivatives (BNA‐X: X=Me, Et, Bzl, Ph, BuBr, and BuTEMPO) aggregate in aqueous methanol. Furthermore, a two‐step emission and aggregation process is controllable by varying the methanol‐to‐water ratio. At 2:3 MeOH/H2O, crystallization‐induced emission enhancement (CIEE) occurs via formation of an emissive crystal phase, whereas, at 1:9 MeOH/H2O, aggregation‐induced emission enhancement (AIEE) occurs, induced by emissive supramolecular nanoparticles (NPs). For BNA‐Ph, the emission quantum yield was 25 times higher in aqueous methanol than that in pure methanol. Despite the high hydrophobicity of BNA‐X (C log P=6.1–8.0), the spherical NPs were monodisperse (polydispersity indices <0.2). Moreover, the emissive NPs exhibited fluorescence resonance energy transfer (FRET) with pyrene; however, for BNA‐X bearing the TEMPO radical (BNA‐BuTEMPO), no FRET was observed because of quenching. In particular, the BNA‐BuTEMPO NPs have a slow rotational correlation time (1.3 ns), suggesting applications as magnetic resonance imaging contrast agents with large relaxivity. [ABSTRACT FROM AUTHOR]

Renal cyclooxygenase (COX) derived eicosanoids are elevated and lipoxygenase (LOX) products are reduced in the Han:SPRD- Cy rat model of polycystic kidney disease (PKD). Selective COX2 inhibition reduces kidney disease progression, but COX1 levels also are elevated in this model. Since the effect of reducing the products of both COX isoforms and the role of LOX products is not known, weanling normal and diseased Han:SPRD- cy littermates were given either low dose acetylsalicylic acid (ASA), nordihydroguaiaretic (NDGA) or no treatment for eight weeks. Renal eicosanoids were altered in the diseased compared to normal cortex, with COX products being higher and LOX products being lower. ASA reduced COX products, cyst growth and kidney water content, while NDGA reduced LOX products without altering disease progression or kidney function. Hence, a human equivalent ASA dose equal to less than one regular strength aspirin per day slowed disease progression, while further reduction of LOX products did not worsen disease progression. [ABSTRACT FROM AUTHOR]

Molecular Recognition Synergistic marriage of self‐assembly and fluorescence (FL) signaling has realized fluorometric readout of dicarboxylates. A newly developed guanidinium‐tethered oligophenylenevinylene (OPV‐G) exhibits characteristic self‐assembling behaviors toward L‐ and meso‐tartarate. Therein, the different self‐assembly modes termed J‐ and H‐type are directed to afford fibrous and finite aggregates, respectively. Such a difference derived from the inherent tartarate structures is eventually embodied as the unique FL responses. For more details, see the Full Paper by T. Noguchi, S. Shinkai et al. on page 13938 ff. [ABSTRACT FROM AUTHOR]

A fluorescent sensor based on guanidinium-tethered tetraphenylethene (TPE) has been investigated toward the differentiation of pyridine nucleotide cofactors (NAD+, NADH, NADP+, and NADPH). TPE selectively recognizes NADPH possessing the higher tetra-anionic net-charge, resulting in the steep 'turn-on' fluorescence increase. The comparative aggregation behaviors and fluorescence response studies of TPE on the four cofactors reveal that the critical aggregate concentration of TPE against NADPH correlates directly with the concentration threshold for the fluorescence response. These results establish that TPE can selectively differentiate NADPH over the other three cofactors by the steep aggregation-induced fluorescence response accompanied by the high signal-to-background contrast. [ABSTRACT FROM AUTHOR]

N,N-Dipyridilaminoxyl, NOpy2, having a stable aminoxyl, was prepared as a new magnetic coupler for heterospin systems. Solutions of NOpy2 were mixed with those of bis{1,1,1,5,5,5, hexafluoro-4-(phenylimino)-2-pentanonate}cobalt derivatives, Co(hfpip-X)2, at a 1:1 ratio to afford the polymeric cobalt(II) complexes, [Co(hfpip-X)2(NOpy2)]n; X = H (1), F (2), F3 (3), F5 (4), Cl (5), Cl3 (6), Br (7), and I (8) as single crystals. In all complexes, the local structures of the cobalt-complex units were compressed octahedra and the pyridine ligands in NOpy2 units coordinated to the cobalt ions in trans configuration to form linear chains for 1-4 and in cis configuration to form helical chains for 5-8. In the chains, the aminoxyl in NOpy2 ferromagnetically interacted with the cobalt ions to produce the ferromagnetic chains with Jintra/kB = 9-14 K. In the magnetic susceptibility experiments of aligned sample of 6, the magnetic easy axis was determined to be the a* axis, which was the direction perpendicular to the b axis of the chain axis. The resulting chains, all except 4, interacted antiferromagnetically among each other, and especially in 1, 5, 7, and 8, the magnetic behaviors characteristic to canted two-dimensional (2D) antiferromagnets with Tc = 5.6, 4.0, 4.0, and 6.2 K, respectively, were observed. All complexes showed slow magnetic relaxations affected by the interchain antiferromagnetic interaction. The effective activation barriers, Δeff/kB, for the reorientation of the magnetism for all complexes except 4 were estimated to be 25-39 K in the presence of a direct current (dc) field. [ABSTRACT FROM AUTHOR]

Background. Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of renal failure. Aberrant epithelial cell proliferation is a major cause of progressive cyst enlargement in ADPKD. Since activation of the Ras/Raf signaling system has been detected in cyst-lining epithelia, inhibition of Raf kinase has been proposed as an approach to retard the progression of ADPKD.Methods and results. PLX5568, a novel selective small molecule inhibitor of Raf kinases, attenuated proliferation of human ADPKD cyst epithelial cells. It reduced in vitro cyst growth of Madin–Darby Canine Kidney cells and of human ADPKD cells within a collagen gel. In male cy/+ rats with polycystic kidneys, PLX5568 inhibited renal cyst growth along with a significant reduction in the number of proliferating cell nuclear antigen- and phosphorylated extracellular signal-regulated kinase-positive cyst-lining epithelial cells. Furthermore, treated animals showed increased capacity to concentrate urine. However, PLX5568 did not lead to a consistent improvement of renal function. Moreover, although relative cyst volume was decreased, total kidney-to-body weight ratio was not significantly reduced by PLX5568. Further analyses revealed a 2-fold increase of renal and hepatic fibrosis in animals treated with PLX5568.Conclusions. PLX5568 attenuated cyst enlargement in vitro and in a rat model of ADPKD without improving kidney function, presumably due to increased renal fibrosis. These data suggest that effective therapies for the treatment of ADPKD will need to target fibrosis as well as the growth of cysts. [ABSTRACT FROM AUTHOR]

Background: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease characterized by renal cyst expansion, resulting in renal failure. With the progression of renal damage, the accumulation of uremic compounds is recently reported to subsequently cause further renal damage and hypertension. Finding uremic toxins and sensitive markers for detecting the early stage of ADPKD is necessary to clarify its pathophysiological process and to prevent its progression. The aim of this study was to analyze the profile of uremic retention solutes of ADPKD by capillary electrophoresis-mass spectrometry (CE-MS) using the Han:SPRD rat model. Methods: Two hundred and ninety-seven cations and 190 anions were comprehensively analyzed by CE-MS in Han:SPRD rats and control rats. Results: We found 21 cations and 19 anions that accumulated significantly in the heterozygous (Cy/+) ADPKD rat model compared with control rats. Among the compounds, increases in 5-methyl-2′-deoxycytidine, glucosamine, ectoine, allantoate, α-hydroxybenzoate, phenaceturate and 3-phenylpropionate and decreases in 2-deoxycytidine, decanoate and 10-hydroxydecanoate were newly identified in the ADPKD Cy/+ rats. Conclusion: We identified uremic retention solutes in ADPKD Cy/+ rats. Compounds related to ADPKD could be useful markers for detecting the early stage of ADPKD. [ABSTRACT FROM AUTHOR]

Han:SPRD Cy is a spontaneous rat model of polycystic kidney disease (PKD) caused by a missense mutation in Pkdr1. Cystogenesis in this model is not clearly understood. In the current study, we performed global gene expression profiling in early-stage PKD cyst development in Cy/Cy kidneys and normal (+/+) kidneys at 3 and 7 days of postnatal age. Expression profiles were determined by microarray analysis, followed by validation with real-time RT-PCR. Genes were selected with over 1.5-fold expression changes compared with age-matched +/+ kidneys for canonical pathway analysis. We found nine pathways in common between 3- and 7-day Cy/Cy kidneys. Three significantly changed pathways were designated "Vitamin D Receptor (VDR)/Retinoid X Receptor (RXR) Activation," "LPS/IL-1-Mediated Inhibition of RXR Function," and "Liver X Receptor (LXR)/RXR Activation." These results suggest that RXR-mediated signaling is significantly altered in developing kidneys with mutated Pkdr1. In gene ontology analysis, the functions of these RXR-related genes were found to be involved in regulating cell proliferation and organ morphogenesis. With real-time RT-PCR analysis, the upregulation of Ptx2, Alox15b, OSP, and PCNA, major markers of cell proliferation associated with the RXR pathway, were confirmed in 3- and 7-day Cy/Cy kidneys compared with 3-day +/+ kidneys. The increased RXR protein was observed in both the nucleus and cytoplasm of cystic epithelial cells in early-stage Cy/Cy kidneys, and the RXR-positive cells were strongly positive for PCNA staining. Taken together, cell proliferation and organ morphogenesis signals transduced by RXR-mediated pathways may have important roles for cystogenesis in early-stage PKD in this Pkdr1-mutated Cy rat. [ABSTRACT FROM AUTHOR]

Cover Feature: Push-Pull Bisnaphthyridylamine Supramolecular Nanoparticles: Polarity-Induced Aggregation and Crystallization-Induced Emission Enhancement and Fluorescence Resonance Energy Transfer (Chem. Eur. J. 9/2021) Keywords: emission; fluorescence; FRET; nanoparticles; radicals EN emission fluorescence FRET nanoparticles radicals 2885 2885 1 02/12/21 20210210 NES 210210 B An organic solution with a push-pull-type fluorophore b , which resembles the shape of a dragon in the cover image, exhibits aggregation-induced emission enhancement upon water addition. Emission, fluorescence, FRET, nanoparticles, radicals. [Extracted from the article]