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Recently low-energy-gap benzoindenothiophene (BIT)-based organic dyes have been experimentally sensitized to dye-sensitized solar cells (DSSCs) with impressive 10.9% power conversion efficiency. This paper presents a computational study of the modification of BIT-based dyes with fused thiophene moieties to build novel low band gap sensitizers. Density functional theory (DFT), tight-binding DFT, and time dependent DFT (TDDFT) approaches are used to demonstrate the electronic and optical properties of the BIT dyes and dye/(TiO2)46 complexes. Our calculations show that the structural modification by using fused thiophenes can effectively lower the band gap of the BIT dyes by 0.07-0.12 eV and affect the optical properties of BIT dyes. Enlarging the thiophene unit in BIT with thienothiophene and dithienothiophene improves the oscillator strength by 14%-25%, while the lowest-energy absorption peak basically remains at 559 nm. The incorporation of cyclopentadithiophene unit leads to a significant 47 nm red-shift of absorption peak and a 25% enhanced oscillator strength, compared to the original BIT dye. Those fused thiophenes modified BIT dyes also demonstrate ideal molecular orbital distribution patterns and ultra-fast injection time at the dye/(TiO2)46 interface. Our calculations provide useful guidance for the molecular design of novel naphthalene-based dyes for DSSC optimizations.
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Promoter is a key DNA element located near the transcription start site, which regulates gene transcription by binding RNA polymerase. Thus, the identification of promoters is an important research field in synthetic biology. Nannochloropsis is an important unicellular industrial oleaginous microalgae, and at present, some studies have identified some promoters with specific functions by biological methods in Nannochloropsis, whereas few studies used computational methods. Here, we propose a method called DNPPro (DenseNet-Predict-Promoter) based on densely connected convolutional neural networks to predict the promoter of Nannochloropsis. First, we collected promoter sequences from six Nannochloropsis strains and removed 80% similarity using CD-HIT for each strain to yield a reliable set of positive datasets. Then, in order to construct a robust classifier, within-group scrambling method was used to generate negative dataset which overcomes the limitation of randomly selecting a non-promoter region from the same genome as a negative sample. Finally, we constructed a densely connected convolutional neural network, with the sequence one-hot encoding as the input. Compared with commonly used sequence processing methods, DNPPro can extract long sequence features to a greater extent. The cross-strain experiment on independent dataset verifies the generalization of our method. At the same time, T-SNE visualization analysis shows that our method can effectively distinguish promoters from non-promoters.
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Redes Neurales de la Computación , Biología Sintética , Regiones Promotoras GenéticasRESUMEN
This study aims to evaluate the clinical application value of two materials, drug-eluting stent, and biodegradable stent, in the treatment of coronary heart disease. The results show that the therapeutic effects of drug-eluting stents and biodegradable stents are similar. Both treatment methods have high safety and effectiveness. The ideal coronary artery stent should have good biocompatibility, safety, and possibility.
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Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Implantes Absorbibles , Materiales Biocompatibles , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Humanos , Intervención Coronaria Percutánea/métodos , Polímeros , Diseño de Prótesis , Sirolimus , Stents , Resultado del TratamientoRESUMEN
We investigate the impact of the delay in compulsory mask wearing on the spread of COVID-19 in the community, set in the Singapore context. By using modified SEIR-based compartmental models, we focus on macroscopic population-level analysis of the relationships between the delay in compulsory mask wearing and the maximum infection, through a series of scenario-based analysis. Our analysis suggests that collective masking can meaningfully reduce the transmission of COVID-19 in the community, but only if implemented within a critical time window of approximately before 80-100 days delay after the first infection is detected, coupled with strict enforcement to ensure compliance throughout the duration. We also identify a delay threshold of about 100 days that results in masking enforcement having little significant impact on the Maximum Infected Values. The results therefore highlight the necessity for rapid implementation of compulsory mask wearing to curb the spread of the pandemic.
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COVID-19 , Pandemias , Humanos , Pandemias/prevención & control , SARS-CoV-2 , Singapur/epidemiologíaRESUMEN
This paper presents a computational study of the adsorptive desulfurization of small aromatic sulfur compounds by conjugated microporous polymers (CMPs). The density-functional tight-binding method augmented with an R-6 dispersion correction is employed to investigate the physisorption binding mechanism and electronic properties of the CMP-aromatic sulfur complexes. We show that the widely extended π conjugation in the CMP skeletons is favorable for the non-covalent adsorption of aromatic thiophene and dibenzothiophene via π-π, H-π, and S-π interactions. The average binding energies are calculated to be -6.2 â¼ -15.2 kcal/mol for CMP- thiophene/dibenzothiophene systems. For the dibenzothiophene molecule with larger size and more extended conjugation, it binds more than twice stronger to CMP than the thiophene molecule. We show that the replacement of quinoline unit to the phenylene group in the network linker effectively enhances the average binding capacities by around 0.8-1.8 kcal/mol. Our calculations theoretically demonstrate that CMPs materials are kind of promising candidates for the adsorptive desulfurization of small aromatic sulfur compounds. This paper provides useful theoretical guidance for design of novel carbon-based adsorbents for adsorptive desulfurization.
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Polímeros , Azufre , Adsorción , Compuestos de AzufreRESUMEN
The rapid development of online social networks not only enables prompt and convenient dissemination of desirable information but also incurs fast and wide propagation of undesirable information. A common way to control the spread of pollutants is to block some nodes, but such a strategy may affect the service quality of a social network and leads to a high control cost if too many nodes are blocked. This paper considers the node selection problem as a biobjective optimization problem to find a subset of nodes to be blocked so that the effect of the control is maximized while the cost of the control is minimized. To solve this problem, we design an ant colony optimization algorithm with an adaptive dimension size selection under the multiobjective evolutionary algorithm framework based on decomposition (MOEA/D-ADACO). The proposed algorithm divides the biobjective problem into a set of single-objective subproblems and each ant takes charge of optimizing one subproblem. Moreover, two types of pheromone and heuristic information are incorporated into MOEA/D-ADACO, that is, pheromone and heuristic information of dimension size selection and that of node selection. While constructing solutions, the ants first determine the dimension size according to the former type of pheromone and heuristic information. Then, the ants select a specific number of nodes to build solutions according to the latter type of pheromone and heuristic information. Experiments conducted on a set of real-world online social networks confirm that the proposed biobjective optimization model and the developed MOEA/D-ADACO are promising for the pollutant spreading control.
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Difusión de la Información , Modelos Biológicos , Red Social , Algoritmos , Heurística Computacional , Contaminantes Ambientales , Internet , Modelos Estadísticos , FeromonasRESUMEN
P-glycoprotein (P-gp), encoded by ABCB1 gene, participants in the transmembrane transport of multiple anticancer drugs. The aim of the current research was to observe in vitro the impacts of ABCB1 (1236 C > T, 2677G > T, and 3435C > T) polymorphisms on the efflux activity of P-gp-mediated sunitinib.Stable recombinant colonic adenocarcinoma cell (Caco-2) systems transfected with ABCB1 wild-type allele and variant alleles (1236 T, 2677T and 3435T) were constructed. The resistance of each cell line to sunitinib was assessed by cell counting kit-8 (CCK8) assay. The effects of ABCB1 (1236 C > T, 2677G > T and 3435C > T) polymorphisms on the intracellular accumulation and transepithelial permeability of sunitinib were also investigated.The recombinant cell lines transfected with ABCB1 variant alleles (1236 T, 2677T, and 3435T) showed higher resistance to sunitinib compared to cells transfecting with ABCB1 wild-type allele (p < .05). The intracellular accumulation of sunitinib was significantly decreased in the three types of recombinant cell lines overexpressing ABCB1 variant alleles in comparison of their wild-type cell lines (p < .05). The transepithelial permeability of sunitinib in recombinant cell systems in transfected with variant alleles was significantly increased compared with cells overexpressing ABCB1 wild-type allele. The P-gp activity in recombinant variant cells is stronger when mediated transport of sunitinib than wild-type counterpart. P-gp encoded by ABCB1 (1236 T, 2677T, and 3435T) variant alleles may be more efficient to transport sunitinib than wild-type allele. Our observation suggests that ABCB1 (1236 C > T, 2677G > T, and 3435C > T) polymorphisms affect the transport ability of P-gp-mediated sunitinib.Collectively, ABCB1 polymorphisms may alter the P-gp-mediated sunitinib sensitivity via regulating drug transport.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Sunitinib/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Células CACO-2 , Humanos , Variantes Farmacogenómicas , Polimorfismo de Nucleótido SimpleRESUMEN
Lenzites betulina has been recognized as a rich source of chemical components, including polysaccharides, sterides and sugar alcohols. In this study, cellulase-ultrasonic synergistic extraction method was applied to extract polysaccharides from L. betulina, and the response surface methodology was used to optimize the extraction conditions. The eight basic factors affecting extraction yield were evaluated by Plackett-Burman design (PBD). Then, the four important factors significantly affecting the yield of polysaccharides from L. betulina, including enzymolysis temperature, enzymolysis time, ultrasound time and ultrasound temperature, were optimized by Box-Behnken design (BBD). Maximum extraction yield of L. betulina polysaccharides was 13.64±0.09 % at a cellulase dosage of 0.8 %, enzymolysis temperature of 60 °C, enzymolysis time of 180â min, pH of 4.5, liquid-solid ratio of 45â ml/g, ultrasound power of 300â W, ultrasound time of 20â min and ultrasound temperature of 45 °C. Subsequently, the characteristic structure of crude polysaccharides was determined by FT-IR. Results indicated that cellulase-ultrasonic synergistic treatment is suitable for L. betulina polysaccharides extraction, and it has good prospect for development and utilization.
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Celulasa/metabolismo , Polyporaceae/química , Polisacáridos/aislamiento & purificación , Ultrasonido , Celulasa/química , Polisacáridos/química , Polisacáridos/metabolismo , TemperaturaRESUMEN
Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6-8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.
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Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Detección Precoz del Cáncer/métodos , Antígenos de Superficie de la Hepatitis B/sangre , Biopsia Líquida/métodos , Neoplasias Hepáticas/diagnóstico , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Ácidos Nucleicos Libres de Células , Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
Unsaturated alcohols and saturated carbonyls are important chemical, pharmaceutical, and biochemical intermediates. We herein report an efficient transfer hydrogenation protocol in which conversion of unsaturated carbonyl compounds to either unsaturated alcohols or saturated carbonyls was catalyzed by Cu(I) N-donor thiolate clusters along with changing hydrogen source (isopropanol or butanol) and base (NaOH or K2CO3). Mechanistic studies supported by DFT transition state modeling indicate that such a chemoselectivity can be explained by the relative concentrations of Cu(I) monohydride and protonated Cu(I) hydride complexes in each catalytic system.
RESUMEN
One hexanuclear Cu(I) cluster of 4,6-dimethylpyrimidine-2-thiolate efficiently catalyzes the dehydrogenative cross-coupling of secondary and primary alcohols to α-alkylated ketones with high selectivity. This transformation proceeds through a one-pot sequence of dehydrogenation of alcohols, condensation of aldehydes and ketones, hydrogenation of the resulting α,ß-unsaturated ketones, and dehydrogenation of the α-alkylated alcohols to generate α-alkylated ketones. This catalytic system also displays high activity for the annulation reaction of secondary alcohols with γ-amino- and 2-aminobenzyl alcohols to yield pyridines and quinolines, respectively.
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To investigate the inhibitory mechanism of quercetin on growth of human bladder cancer cell line(BIU-87). BIU-87 cells were cultured in vitro, and co-cultured with varying concentrations of quercetin, and the anti-proliferative activity was determined by CCK-8 assay. Apoptosis of quercetin-induced BIU-87 cells and cell cycle were determined by flow cytometry analysis. Expressions of Bal-2 and Bal-xL, and related proteins in TAK1/JNK signal pathway were measured using Western blot analysis. After treatment with quercetin for 24 h and 48 h, the proliferation of BIU-87 cells was significantly suppressed in a dose-dependent manner according to CCK-8 assay(P<0.05). The flow cytometry analysis indicated that each group of quercetin leads to a significant higher percentage of apoptosis of BIU-87 cells than control group after treatment with quercetin for 24 h and 48 h; In G0/G1 period, cells reduced, while the amount of cells in G2/M period increased, and cells in S period remained the same amount. Expressions of Bal-2, Bal-xL, p-TAK1, p-MKK4/7, p-JNK decreased in BIU-87 cells after treatment with quercetin. Quercetin could inhibit the proliferation and promote the apoptosis of BIU-87 cells. The mechanism may be correlated with the inhibition of TAK1/JNK signaling pathway, which led to the further decrease in expressions of Bal-2 and Bal-xL.
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Apoptosis/efectos de los fármacos , Quercetina/farmacología , Neoplasias de la Vejiga Urinaria/patología , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Proliferación Celular , Humanos , Transducción de SeñalRESUMEN
Reactions of a pincer ligand 2-(1H-pyrazol-1-yl)-6-(1H-pyrazol-3-yl)pyridine (pzpypzH) with Cu(NO3)2, Cu(ClO4)2, CuSO4, CuCl2 or CuI produced three dinuclear Cu(ii) complexes [{Cu(NO3)}(µ-pzpypz)]2 (1), [{Cu(ClO4)}(µ-pzpypz)]2 (2), [Cu2(µ-SO4)(µ-pzpypz)2]·2MeOH (3·2MeOH), one mononuclear Cu(ii) complex [CuCl2(pzpypzH)] (4) and one trinuclear Cu(i)/Cu(ii) complex [(ICu)(µ-I)2Cu2(µ-pzpypz)2] (5), respectively. Treatment of 4 with two equiv. of AgNO3 in DMF also gave rise to 1. Complexes 1-5 were characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. Complex 1 or 2 has a dimeric structure in which two {Cu(X)} (X = NO3, ClO4) fragments are interconnected by two µ-pzpypz(-) ligands. 3 also adopts a dimeric structure in which two Cu(ii) centers are interconnected by a pair of µ-pzpypz(-) ligands and one µ-SO4(2-) ion. The Cu(ii) center in 4 is five-coordinated by three N atoms of the pzpypzH ligand and two Cl atoms. In 5, two Cu(ii) centers are bridged by two µ-pzpypz(-) ligands and one CuI3(2-) unit, forming a unique trinuclear structure. Complexes 1-5 displayed high catalytic activity toward the ammoxidation of alcohols to nitriles and the aerobic oxidation of alcohols to aldehydes in H2O. The nitrile or aldehyde products could be readily separated from the catalytic system by extraction and the residual aqueous solution containing 1 retained good activity for several cycles.
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Five new glucosylated steroidal glycosides, cantalasaponin I-B(1) (1), I-B(2) (2), I-B(3) (3), I-B(4) (4) and I-B(5) (5), were isolated and purified from the transformed product of the cantalasaponin I by using Toruzyme 3.0 l as biocatalyst. Their structures were elucidated on the basis of high-resolution electrospray ionization mass spectrometry, one-dimensional ((1) H and (13) C NMR) and two-dimensional [COSY, heteronuclear single-quantum correlation (HSQC), HMBC and HSQC-TOCSY] NMR spectral analyses and chemical evidence.
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Saponinas/química , Biocatálisis , Glucosiltransferasas/química , Glucosiltransferasas/metabolismo , Glicosilación , Espectroscopía de Resonancia Magnética/normas , Estructura Molecular , Estándares de Referencia , Saponinas/aislamiento & purificación , Saponinas/metabolismoRESUMEN
Five new steroidal glycosides, timosaponin J ( 1), timosaponin K ( 2), (25 S)-karatavioside C ( 5), timosaponin L ( 6), and (25 S)-officinalisnin-I ( 8), together with eight known steroidal saponins, timosaponin E (1) ( 3), purpureagitosid ( 4), timosaponin BII ( 7), timosaponin B III ( 9), anemarrhenasaponin I ( 10), anemarrhenasaponin III ( 11), anemarrhenasaponin A (2) ( 12), and timosaponin A III ( 13), were isolated from the rhizomes of Anemarrhena asphodeloides. Their structures were elucidated on the basis of spectroscopic and chemical evidence. The aglycones of compounds 1 and 2 are new aglycones. Compounds 1- 13 were evaluated for their platelet aggregation activities, and compound 13 exhibited the strongest inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation.
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Anemarrhena/química , Glicósidos/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Esteroides/farmacología , Adenosina Difosfato/farmacología , Animales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Glicósidos/química , Glicósidos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Masculino , Estructura Molecular , Plantas Medicinales/química , Ratas , Ratas Wistar , Rizoma/química , Saponinas/química , Saponinas/aislamiento & purificación , Saponinas/farmacología , Esteroides/química , Esteroides/aislamiento & purificaciónRESUMEN
Steroidal saponins in Rhizoma Paridis attract scientific attentions for their structural diversity and significant bioactivities. In this work, an ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used to rapidly separate and identify steroidal saponins from the extract of the rhizome of Paris polyphylla var. yunnanensis (PPY). The fragment ions from glycosidic and cross-ring cleavages offered a wealth of structural information that is indicative to the aglycones, sugar types and the connecting sequence of sugar units. Based on the exact mass information, the fragmentation characteristics, and the LC retention times of 21 reference steroidal saponin standards, 98 constituents were tentatively identified with their structures proposed, which covered more than 30 types of steroidal aglycones. The 98 constituents consist of 22 pairs of structural isomers, and 40 steroidal glycosides that are identified for the first time from the nature.
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Cromatografía Liquida/métodos , Glicósidos/análisis , Magnoliopsida/química , Extractos Vegetales/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Esteroides/análisis , Secuencia de Carbohidratos , Glicósidos/química , Datos de Secuencia MolecularRESUMEN
Nine spirostanol saponins (1-9) and seven mixtures of 25 R and 25 S spirostanol saponin isomers (10-16) were obtained from the seeds of Trigonella foenum-graecum after enzymatic hydrolysis of the furostanol saponin fraction by ß-glucosidase. Their structures were determined by NMR and MS spectroscopy. Among them, 1- 4, 6, 8, and 9 were new compounds and five, 11B, 12A, 13B, 14A, and 14B, were new structures observed from seven mixtures. In addition, the inhibitory effects of all saponins on rat platelet aggregation were evaluated.
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Agregación Plaquetaria/efectos de los fármacos , Saponinas/farmacología , Espirostanos/farmacología , Trigonella/química , beta-Glucosidasa/química , Animales , Medicamentos Herbarios Chinos/farmacología , Hidrólisis , Masculino , Estructura Molecular , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Saponinas/química , Saponinas/aislamiento & purificación , Semillas/química , Espirostanos/química , Espirostanos/aislamiento & purificación , beta-Glucosidasa/metabolismoRESUMEN
This study was aimed to investigate the effect of bortezomib alone or combined with arsenic trioxide on the apoptosis of Jurkat cells and expression of livin mRNA. The Jurkat cells were cultured and treated with different concentrations of bortezomib, arsenic trioxide or their combination for 24 hours. Then, the expression of livin mRNA was detected by RT-PCR, the cell proliferation was analyzed with MTT assay and flow cytometry. The results showed that 5 - 25 nmol/L bortezomib could effectively inhibit Jurkat cells in a dose-dependent manner, the group of bortezomib combined with arsenic trioxide showed more inhibitory effect on Jurkat cells than the effect of bortezomib alone or arsenic trioxide alone on Jurkat cells. The expression of livin mRNA in Jurkat cells decreased in a dose-dependent manner after treated with bortezomib, which was downregulated significantly after combined treatment. It is concluded that bortezomib and arsenic trioxide can induce apoptosis by inhibiting the expression of livin mRNA in Jurkat cells. The combination of bortezomib with arsenic trioxide displays a synergistic effect.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Apoptosis/efectos de los fármacos , Arsenicales/farmacología , Ácidos Borónicos/farmacología , Proteínas Inhibidoras de la Apoptosis/metabolismo , Proteínas de Neoplasias/metabolismo , Óxidos/farmacología , Pirazinas/farmacología , Proteínas Adaptadoras Transductoras de Señales/genética , Trióxido de Arsénico , Ácidos Borónicos/administración & dosificación , Bortezomib , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Células Jurkat , Proteínas de Neoplasias/genética , Pirazinas/administración & dosificación , ARN Mensajero/genéticaRESUMEN
OBJECTIVES: To investigate the effect of interferon (IFN)-γ administration on renal interstitial fibrosis (RIF) and intrarenal vascular resistance of diseased kidneys in a reversible unilateral ureteral obstruction (RUUO) animal model. METHODS: Thirty-six male Sprague-Dawley rats were randomly divided into three groups: RUUO with intramuscular IFN-γ treatment (400 IU/d; RUUO + IFN), RUUO with vehicle treatment, and sham operation. RUUO was induced by clamping the left ureter using a small polyethylene tube. The obstruction was reversed seven days after the operation by removing the tube. Six animals in each group were killed at days 7 and 14. The intrarenal resistive index (RI) of diseased kidneys was measured by colored Doppler flow imaging. RIF was evaluated using Masson's trichrome staining. RESULTS: The obstruction was successfully reversed in all animals. At day 7, the RIF scores were 32.1 ± 3.1 and 40.3 ± 3.1 in the RUUO + IFN group and the RUUO group, respectively. The RI increased by 87% in the RUUO group and by 64% in the RUUO + IFN group compared with sham. At day 14, the RIF scores decreased to 24.6 ± 3.9 in the RUUO + IFN group, but increased to 50.8 ± 4.4 in the RUUO group. The increase of RI was reduced to 64% in the RUUO group and to 20% in the RUUO + IFN group. Ureteral obstruction induced few lesions in the contralateral kidneys, and IFN-γ administration had no significant effect on them, although it exerted an antifibrotic effect on the obstructed kidneys. CONCLUSIONS: IFN-γ administration restored or preserved renal histology and hemodynamics in an animal model of renal fibrosis after surgical reversal of hydronephrosis.
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Hidronefrosis/patología , Interferón gamma/farmacología , Riñón/patología , Circulación Renal/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Modelos Animales de Enfermedad , Fibrosis , Hidronefrosis/etiología , Hidronefrosis/fisiopatología , Riñón/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/patología , Obstrucción Ureteral/fisiopatologíaRESUMEN
OBJECTIVE: ⢠To compare the expressions of common fibrosis-relevant genes in hydronephrosis-induced fibrotic renal tissues and normal human renal tissues, thereby providing insights into the cellular and molecular mechanisms of renal fibrosis resulting from hydronephrosis. PATIENTS AND METHODS: ⢠A total of 12 extensively fibrotic renal tissue samples from patients with hydronephrosis (H-group) and six normal renal tissue samples from patients who underwent nephrectomy for renal cell carcinoma (N-group), along with their clinical data, were collected at Renmin Hospital of Wuhan University in China between October 2005 and August 2007. ⢠These tissue samples were compared for their transforming growth factor-ß (TGF-ß)/bone morphogenetic protein (BMP) pathway-related gene profiles using a real-time polymerase chain reaction (PCR) microarray. ⢠Subsequently, reverse transcriptase-PCR assays were used to validate the expression changes of left-right determination factor (LEFTY), a gene of interest, at the mRNA level. ⢠The different expression of LEFTY at the protein level was confirmed by western blotting and immunohistochemistry assays. RESULTS: ⢠The results showed that 49 genes were differently expressed in fibrotic renal tissues relative to normal control tissues. Among these genes, 25 were up-regulated and 24 were down-regulated. ⢠LEFTY-B, one of the most markedly altered genes, was down-regulated 13.55-fold compared with N-group tissues. ⢠RT-PCR showed that the LEFTY-A (6.05-fold down-regulated, P < 0.001) and LEFTY-B (12.5-fold down-regulated, P < 0.001) genes, two members of the LEFTY family in human tissues, were both significantly down-regulated in H-group tissues. ⢠Similarly, down-regulations of LEFTY-A (0.25-fold vs N-group, P < 0.001) and LEFTY-B (0.20-fold vs N-group, P < 0.001) proteins were detected by western blotting (P < 0.001). ⢠Immunohistochemical staining showed different distributions of LEFTY in the two tissue samples, and quantitative image analyses confirmed that LEFTY protein expression was lower in H-group tissues than in N-group tissues (P < 0.001). CONCLUSIONS: ⢠The gene and protein expressions of LEFTY were found to be down-regulated in extensively fibrotic renal tissues induced by hydronephrosis. ⢠LEFTY may represent an ideal candidate for a therapeutic target for renal fibrosis.