RESUMEN
Polyetheretherketone (PEEK) is a polymer material composed of aromatic rings connected by ether and ketone groups. It has advantages of excellent biocompatibility, stable chemical properties, and appropriate elasticity modulus. Since PEEK are increasingly used in dentistry in recent years, the properties, modification methods, and research advances of them in oral implantology were discussed in this review.
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Implantes Dentales , Polímeros , Cetonas/química , Polietilenglicoles/química , ÉteresRESUMEN
Myeloid-derived suppressor cells (MDSCs) as an important population of immune cells were found to restrain T cell function, polarize T-helper cells (Th) 1/Th2 toward Th2 response and induce regulatory T cells (Tregs), therefore enhancing the immunotolerance during pregnancy. Sildenafil has been applied for poor endometrial quality in implantation failure patients. Nevertheless, investigations have shown that sildenafil could reduce MDSCs-dependent immunosuppression. Whether sildenafil affects embryo implantation by suppressing MDSCs? To address this question, using the mice model, we investigated the amounts of immune cells in peripheral blood and endometrial cells from control group (CG), sildenafil low-dose group (LDG) and high-dose group (HDG). We found that both treatment groups displayed a marked deficiency in polymorphonuclear (PMN)-MDSCs and Th2 from mice blood and endometrium as compared to these from CG. The frequency of Tregs in endometrium from HDG was lower than those from CG. Th1/Th2 ratio in both periphery and uterus from study groups showed a significant increase as compared to those from CG. By relevance analysis, we found that the level of Tregs positively correlated with the level of PMN-MDSCs, whereas the Th1/Th2 ratio negatively correlated with the frequency of PMN-MDSCs in uterus. Moreover, there was a positive relationship between the amount of blood PMN-MDSCs and endometrial PMN-MDSCs. These results suggest that we should carefully weigh the pros and cons of using sildenafil when applied to patients with poor endometrial receptivity.
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Implantación del Embrión/efectos de los fármacos , Fertilización In Vitro/métodos , Tolerancia Inmunológica/efectos de los fármacos , Células Supresoras de Origen Mieloide/inmunología , Citrato de Sildenafil/efectos adversos , Animales , Implantación del Embrión/inmunología , Endometrio/efectos de los fármacos , Endometrio/inmunología , Femenino , Ratones , Modelos Animales , Células Supresoras de Origen Mieloide/efectos de los fármacos , Embarazo , Citrato de Sildenafil/administración & dosificación , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
BACKGROUND AND PURPOSE: Migraine is a complex and disabling neurological disorder, the exact neurological mechanisms of which remain unclear. The thalamus is considered to be the hub of the central processing and integration of nociceptive information, as well as the modulation of these processes. METHODS: A total of 48 migraineurs without aura (MWoAs) during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized masked independent component analysis and seed-based functional connectivity (FC) to investigate whether MWoAs exhibited abnormal FC between subregions in the thalamus and the cortex regions. RESULTS: The MWoAs showed significantly weaker FC between the anterior dorsal thalamic nucleus and left precuneus. Additionally, MWoAs exhibited significantly reduced FC between the ventral posterior nucleus (VPN) and left precuneus, right inferior parietal lobule (R-IPL) and right middle frontal gyrus. Furthermore, the FC Z-scores between the VPN and R-IPL were negatively correlated with pain intensity in MWoAs. The disease duration of patients was negatively correlated with the FC Z-scores between the VPN and R-IPL. CONCLUSION: These altered thalamocortical connectivity patterns may contribute to multisensory integration abnormalities, deficits in pain attention, cognitive evaluation and pain modulation. Pain sensitivity and disease duration are closely tied to abnormal FC between the VPN and R-IPL. Remarkably, recurrent headache attacks might contribute to this maladaptive functional plasticity closely related to pain intensity.
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Migraña sin Aura , Corteza Cerebral/diagnóstico por imagen , Epilepsia , Humanos , Imagen por Resonancia Magnética , Migraña sin Aura/diagnóstico por imagen , Tálamo/diagnóstico por imagenRESUMEN
Eleven single nucleotide polymorphisms (SNP) in Ctenopharyngodon idella toll-like receptor 7 (citlr7) gene, containing two in the 5'-flanking region, three within the single intron and six distributed in the coding sequence (CDS), were identified. A case-control study of 73 susceptible individuals and 67 resistant individuals was conducted to test the SNPs-based susceptibility-resistance association and mRNA expression of citlr7 to grass carp reovirus (GCRV), showing that both 820 A/G and 1726 A/G were significantly correlative sites in genotype (P < 0·05). Multifactor dimensionality reduction (MDR) analysis suggested the exertion of antiviral effects of 820 A/G might rely on SNPs interactions of citlr7 and C. idella toll-like receptor 8 (citlr8). Combining the mortality rate and citlr7 mRNA expression, it was suggested that 1726 GG-genotyped individuals might be more resistant than 1726 A/G genotyped individuals, indicating the selection on synonymous mutations in 1726 A/G might be susceptibility-resistance-type specific. In addition, haplotype analysis uncovered no significantly correlative haplotypes in citlr7. These findings may provide an in-depth insight for the further functional research of citlr7. The potential genetic markers identified may contribute to the molecular and transgenic breeding of C. idella.
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Carpas/inmunología , Susceptibilidad a Enfermedades , Enfermedades de los Peces/inmunología , Proteínas de Peces/genética , Polimorfismo de Nucleótido Simple , Infecciones por Reoviridae/inmunología , Receptor Toll-Like 7/genética , Animales , Carpas/genética , Carpas/metabolismo , Enfermedades de los Peces/genética , Proteínas de Peces/metabolismo , Proteínas de Peces/fisiología , Predisposición Genética a la Enfermedad , Haplotipos , ARN Mensajero/metabolismo , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 7/fisiología , Receptor Toll-Like 8/genética , Receptor Toll-Like 8/metabolismo , Receptor Toll-Like 8/fisiologíaRESUMEN
Objective: To compare and evaluate the curative effect of laparoscopic distal pancreatectomy(LDP) and traditional open distal pancreatectomy(ODP) in pancreatic ductal adenocarcinoma. Methods: The clinical data of 15 patients treated by LDP and 87 contemporaneous cases treated by ODP from January 2010 to November 2015 was collected, and the curative effect and prognosis of these patients were retrospectively analyzed. Results: The operation time of LDP group was (286.5±48.1) min, significantly longer than that of OPD group(226.6±56.8) min (P<0.05). The operative hemorrhage, postoperative exhaust time, recovery eating time, the whole and postoperative hospitalization time of LDP group were (188.7±108.9) ml, (2.2±1.3) d, (2.9±1.1) d, (13.2±10.4) d and (9.3±8.1) d, respectively, dramatically shorter than those of ODP group (625.2±982.1) ml, (4.3±1.7) d, (5.2±1.8) d, (20.7±8.7) d and (14.9±7.8) d, respectively (all of P<0.05). There were no intraoperative blood transfusion case in LDP group, however, 13 patients in ODP group received intraoperative blood transfusion, without significant difference (P=0.207). Alternatively, 6 cases occurred pancreatic fistula in LDP group, among them, 5 cases were grade A and 1 case was grade B; In ODP group, 17 cases occurred pancreatic fistula, among them 13 cases were grade A, 1 case was grade B and 3 cases were grade C, without significant differences (P=0.130). There were 2 cases of delayed gastric empty, 1 case of pulmonary infection in LDP group. In ODP group, there were 5 cases of postoperative delayed gastric empty, 3 cases of pulmonary infection and 6 cases of intra-abdominal infection, without significant differences (P>0.05). In both LDP group and ODP group, none occurred percutaneous drainage, re-admissions, second operation or perioperative death. Conclusions: Compared to ODP, LDP is much safer and more steady in perioperative periodand operation. Patients of pancreatic ductal adenocarcinoma received LDP can acquire more benefit and recovery sooner, and LDP is a safe and effective operative method.
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Carcinoma Ductal Pancreático/cirugía , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Humanos , Laparoscopía , Tiempo de Internación , Masculino , Tempo Operativo , Pancreatectomía/efectos adversos , Fístula Pancreática/etiología , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The present study was conducted to analyze the correlation between ultrasonic characteristics, pathological type, and molecular markers of thyroid-tumor-related genes as well as to evaluate the diagnosis and prognosis of thyroid nodules. The acoustic characteristics of 130 thyroid specimens were detected. Pathological sectioning and immunohistochemical detection were performed to determine the correlation between tumor gene expression and ultrasonic characteristics. Ultrasonic testing revealed that malignant nodules were normally accompanied by lymph nodes. Expression of the human telomerase reverse transcriptase, Ki67, vascular endothelial growth factor, Ret, and P53 genes exhibited statistically significant differences in malignant, benign, and normal tissues. The performance of thyroid malignant nodules showed different degrees of correlation with the expression of the human telomerase reverse transcriptase, Ki67, VEGF, Ret, and P53 genes. Color Doppler ultrasound is highly sensitive for thyroid nodules and is therefore effective for identifying thyroid nodules and early diagnosis of thyroid cancer. Color Doppler ultrasound can identify benign or malignant thyroid nodules based on 5 characteristic indicators. Tumor pathology and gene expression are associated with the sonographic features of thyroid cancer. Therefore, determining the pathological basis of ultrasonography would facilitate prognostic assessments of thyroid cancer.
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Biomarcadores de Tumor/metabolismo , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Adulto , Anciano , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Antígeno Ki-67/metabolismo , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Proteínas Proto-Oncogénicas c-ret/metabolismo , Telomerasa/metabolismo , Nódulo Tiroideo/genética , Nódulo Tiroideo/cirugía , Proteína p53 Supresora de Tumor/metabolismo , Ultrasonido , Ultrasonografía Doppler en Color , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The Lunar Exploration Neutron Detector (LEND), on the polar-orbiting Lunar Reconnaissance Orbiter (LRO) spacecraft, has detected suppression in the Moon's naturally-occurring epithermal neutron leakage flux that is consistent with the presence of diurnally varying quantities of hydrogen in the regolith near the equator. Peak hydrogen concentration (neutron flux suppression) is on the dayside of the dawn terminator and diminishes through the dawn-to-noon sector. The minimum concentration of hydrogen is in the late afternoon and dusk sector. The chemical form of hydrogen is not determinable from these measurements, but other remote sensing methods and anticipated elemental availability suggest water molecules or hydroxyl ions. Signal-to-noise ratio at maximum contrast is 5.6σ in each of two detector systems. Volatiles are deduced to collect in or on the cold nightside surface and distill out of the regolith after dawn as rotation exposes the surface to sunlight. Liberated volatiles migrate away from the warm subsolar region toward the nearby cold nightside surface beyond the terminator, resulting in maximum concentration at the dawn terminator. The peak concentration within the upper ~1 m of regolith is estimated to be 0.0125 ± 0.0022 weight-percent water-equivalent hydrogen (wt% WEH) at dawn, yielding an accumulation of 190 ± 30 ml recoverable water per square meter of regolith at each dawn. Volatile transport over the lunar surface in opposition to the Moon's rotation exposes molecules to solar ultraviolet radiation. The short lifetime against photolysis and permanent loss of hydrogen from the Moon requires a resupply rate that greatly exceeds anticipated delivery of hydrogen by solar wind implantation or by meteoroid impacts, suggesting that the surface inventory must be continually resupplied by release from a deep volatile inventory in the Moon. The natural distillation of water from the regolith by sunlight and its capture on the cold night surface may provide energy-efficient access to volatiles for in situ resource utilization (ISRU) by direct capture before volatiles can enter the surface, eliminating the need to actively mine regolith for volatile resource recovery.
RESUMEN
Nicotianamine (NA) is a ubiquitous metabolite in plants that bind heavy metals, is crucial for metal homeostasis, and is also an important metal chelator that facilitates long-distance metal transport and sequestration. NA synthesis is catalyzed by the enzyme nicotianamine synthase (NAS). Eruca vesicaria subsp sativa is highly tolerant to Ni, Pb, and Zn. In this study, a gene encoding EvNAS was cloned and characterized in E. vesicaria subsp sativa. The full-length EvNAS cDNA sequence contained a 111-bp 5'-untranslated region (UTR), a 155-bp 3'-UTR, and a 966-bp open reading frame encoding 322-amino acid residues. The EvNAS genomic sequence contained no introns, which is similar to previously reported NAS genes. The deduced translation of EvNAS contained a well-conserved NAS domain (1-279 amino acids) and an LIKI-CGEAEG box identical to some Brassica NAS and to the LIRL-box in most plant NAS, which is essential for DNA binding. Phylogenetic analysis indicated that EvNAS was most closely related to Brassica rapa NAS3 within the Cruciferae, followed by Thlaspi NAS1, Camelina NAS3, and Arabidopsis NAS3. A reverse transcription-polymerase chain reaction indicated that EvNAS expression was greatest in the leaves, followed by the flower buds and hypocotyls. EvNAS was moderately expressed in the roots.
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Transferasas Alquil y Aril/genética , Secuencia de Aminoácidos/genética , Brassicaceae/enzimología , Filogenia , Transferasas Alquil y Aril/biosíntesis , Clonación Molecular , ADN Complementario/genética , Regulación de la Expresión Génica de las Plantas , Hierro/metabolismo , Hojas de la Planta/genética , Raíces de PlantasRESUMEN
ADP-glucose pyrophosphorylase (ADPGlcPPase) controls the first committed step of starch synthesis by catalyzing the biosynthesis of ADP-glucose from glucose-phosphate and ATP. It is a tetrameric protein consisting of two small and two large subunits. The small subunits have a catalytic function, while the large subunits regulate the enzyme activity. Cyperus esculentus (yellow nutsedge) is a perennial C4 plant grown from rhizomes and tubers. Previous studies on yellow nutsedge have mostly focused on the morphology and cultivation of tubers, their application in food, and biochemical analyses of the tubers. In this study, the gene encoding the ADPGlcPPase small subunit (CeAGPS) in yellow nutsedge was cloned and characterized. The full-length CeAGPS cDNA sequence contained an 81-bp 5'-untranslated region (UTR), a 188-bp 3'-UTR, and a 1539-bp open reading frame encoding 512-amino acid residues. The genomic sequence of CeAGPS comprises a nine exon-eight intron structure similar to the previously reported cotton and Arabidopsis thaliana AGPS genes. The deduced translation product of the CeAGPS gene contained a well-conserved catalytic domain and regulatory elements typical of plant AGPS. Reverse transcriptase polymerase chain reaction amplification of the target gene in various plant parts using gene-specific primers indicated that the expression of CeAGPS was most abundant in the tuber, and relatively lower in nutsedge roots.
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Clonación Molecular , Cyperus/genética , Glucosa-1-Fosfato Adenililtransferasa/genética , Subunidades de Proteína/genética , Secuencia de Aminoácidos , Secuencia de Bases , Cyperus/clasificación , Cyperus/metabolismo , ADN Complementario/genética , Regulación de la Expresión Génica de las Plantas , Glucosa-1-Fosfato Adenililtransferasa/química , Glucosa-1-Fosfato Adenililtransferasa/metabolismo , Especificidad de Órganos/genética , Filogenia , Subunidades de Proteína/metabolismo , Análisis de Secuencia de ADNRESUMEN
A farm-scale biogas desulfurization system was designed and tested for H2S removal efficiency from livestock biogas. This work assesses the H2S removal efficiency of a novel farm-scale biogas bio-desulfurization system (BBS) operated for 350 days on a 1,000-head pig farm. Experimental data demonstrated that suitable humidity and temperature can help sulfur-oxidizing bacteria to form active bio-films on the bio-carriers. The daily average removal rate increased to 879.16 from 337.75 g-H2S/d with an average inlet H2S concentration of 4,691 ± 1,532 mg/m(3) in biogas. Thus, the overall (0-350 days) average H2S removal efficiency exceeded 93%. The proposed BBS overcomes limitations of H2S in biogas when utilizing pig farm biogas for power generation and other applications.
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Reactores Biológicos , Sulfuro de Hidrógeno/aislamiento & purificación , Estiércol , Azufre/metabolismo , Administración de Residuos , Crianza de Animales Domésticos , Animales , Biopelículas , Biocombustibles , Humedad , Oxidación-Reducción , Porcinos , TemperaturaRESUMEN
AIMS: To functionally express the recombinant mouse insulin-like growth factor-I (rtmIGF-I) in Lactococcus lactis NZ9000 with a food-grade vector. METHODS AND RESULTS: The rtmIGF-I encoding sequence was inserted into secreted food-grade vector pLEB688 and transformed into L. lactis NZ9000. The expression of the recombinant protein rtmIGF-I was confirmed by tricine-SDS-PAGE analysis and Western blot. The concentration of this recombinant protein was 3 mg l(-1) in the medium fraction. Further experiment demonstrated that the recombinant protein was biologically active and promoted NIH3T3 cell proliferation in a concentration-dependent manner. CONCLUSIONS: The rtmIGF-I was expressed in L. lactis and located into the medium fraction. The optimal final concentration which could promote NIH3T3 cell proliferation after incubation was 100 ng ml(-1) . SIGNIFICANCE AND IMPACT OF THE STUDY: The rtmIGF-I was functionally expressed in L. lactis NZ9000 with a food-grade vector. Thus, the recombinant L. lactis NZ9000 could act as a host for the production of rtmIGF-I for further study. The recombinant strain could serve as an IGF-I delivery system.
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Factor I del Crecimiento Similar a la Insulina/metabolismo , Lactococcus lactis/metabolismo , Animales , Western Blotting , Electroforesis en Gel de Poliacrilamida , Vectores Genéticos , Factor I del Crecimiento Similar a la Insulina/genética , Lactococcus lactis/genética , Lactococcus lactis/crecimiento & desarrollo , Ratones , Células 3T3 NIH , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Somatomedinas/genética , Somatomedinas/metabolismoRESUMEN
The tree shrews are non-rodent, primate-like, small animals. There is increasing interest in using them to establish animal models for medical and biological research. This review focuses on the use of the tree shrews in in vivo studies on viral hepatitis, hepatocellular carcinoma (HCC), myopia, and psychosocial stress. Because of the susceptibility of the tree shrews (Tupaia belangeri) and their hepatocytes to infection with human hepatitis B virus (HBV) in vivo and in vitro, these animals have been used to establish human hepatitis virus-induced hepatitis and human HBV- and aflatoxin B1-associated HCC models. As these animals are phylogenetically close to primates in evolution and have a well-developed visual system and color vision in some species, they have been utilized to establish myopia models. Because dramatic behavioral, physiological, and neuroendocrine changes in subordinate male tree shrews are similar to those observed in depressed human patients, the tree shrews have been successfully employed to experimentally study psychosocial stress. However, the tree shrews holds significant promise as research models and great use could be made of these animals in biomedical research.
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Investigación Biomédica , Modelos Animales de Enfermedad , Tupaiidae/fisiología , Animales , Humanos , Neoplasias Hepáticas Experimentales , Miopía , Tupaiidae/virología , VirosisRESUMEN
AIMS: This study attempted to demonstrate nitrite interference on chemical oxygen demand (COD) determination in piggery wastewater, and the capability of aerobic denitrification of the SU2 strain which is capable of promoting the efficiency of nitrogen and COD removal from piggery wastewater. METHODS AND RESULTS: This study was performed in a 17-litre reactor with a 30% packing ratio, with a ratio of immobilized SU2 cells to sludge of 100:1. The ratio of aeration to nonaeration was 4 : 1.5. Removal efficiency of COD was 86.8%. Removal efficiency of BOD and SS was higher than 90%, and removal efficiency of NH4+-N and TKN was almost 100%. CONCLUSIONS: NO2- -N interference is significant when its concentration in piggery wastewater exceeds 100 mg l-1. COD in piggery wastewater can be indirectly reduced following nitrite reduction by SU2 strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Utilizing immobilized SU2 cells in coordination with an SBR system simultaneously reduces nitrite and COD concentrations.
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Nitritos/metabolismo , Oxígeno/metabolismo , Pseudomonas/metabolismo , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos/métodos , Aerobiosis , Crianza de Animales Domésticos , Animales , Reactores Biológicos , Nitratos/metabolismo , Pseudomonas/crecimiento & desarrollo , PorcinosRESUMEN
AIMS: To isolate aerobic denitrifying bacteria which will be applied to piggery wastewater treatment facilities for enhanced nitrate and nitrite removal. METHODS AND RESULTS: Nitrate-supplemented basal medium in airtight, crimp-sealed serum bottles containing an atmosphere of 92% oxygen was inoculated with denitrifiers, strains NS-2 and SM-3, and incubated at 30 degrees C. After 20 h, the concentration of nitrate was decreased rapidly by both NS-2 and SM-3. Nitrite production was almost zero during the whole experimental period for both strains. Nitrogen gas production peaked at the 20 h for both NS-2 (8.20 +/- 1.03 mmol l(-1)) and SM-3 (3.93 +/- 0.16 mmol l(-1)). CONCLUSIONS: Strain NS-2, which produced the highest N2 concentration in this work, was identified as Pseudomonas stutzeri. This strain is the most capable of aerobic and anaerobic conversion of nitrate to N2 without forming a nitrite intermediate. SIGNIFICANCE AND IMPACT OF THE STUDY: Strain NS-2 is highly promising for future application in in situ piggery wastewater treatment.
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Crianza de Animales Domésticos , Nitratos/metabolismo , Pseudomonas/crecimiento & desarrollo , Pseudomonas/aislamiento & purificación , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos , Aerobiosis , Animales , Técnicas Bacteriológicas , Medios de Cultivo , Residuos Industriales , Oxidación-Reducción , Pseudomonas/clasificación , Porcinos , TaiwánRESUMEN
AIMS: This study compares the ability of Thiosphaera pantotropha ATCC 35512 and the newly isolated Pseudomonas stutzeri SU2 to perform aerobic denitrification. METHODS AND RESULTS: Nitrate-supplemented basal medium in airtight crimp-sealed serum bottles containing an atmosphere of 92% oxygen was inoculated with Ps. stutzeri SU2 or T. pantotropha and incubated at 30 degrees C. During the 92-h incubation period, aerobic denitrification by Ps. stutzeri SU2 (NO3(-) - N removal 99.24%) was more efficient than that by T. pantotropha (NO3(-) - N removal 27.29%). CONCLUSION: Pseudomonas stutzeri SU2, which was isolated from the activated sludge of a sequencing batch reactor treating piggery wastewater, rapidly reduced the nitrate to nitrogen gas without nitrite accumulation. The nitrate removal rate of SU2 was 0.032 mmol NO3(-) - N g cell-1 h-1 after 44 h incubation. SIGNIFICANCE AND IMPACT OF THE STUDY: Pseudomonas stutzeri SU2 can be used in a full-scale sequencing batch system for efficient in situ aerobic nitrate removal from piggery wastewater.
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Bacterias Gramnegativas Quimiolitotróficas/metabolismo , Nitratos/metabolismo , Oxígeno/farmacología , Pseudomonas/metabolismo , Aguas del Alcantarillado/microbiología , Aerobiosis , Crianza de Animales Domésticos , Medios de Cultivo , Bacterias Gramnegativas Quimiolitotróficas/crecimiento & desarrollo , Residuos Industriales , Pseudomonas/crecimiento & desarrollo , Pseudomonas/aislamiento & purificación , Eliminación de Residuos LíquidosRESUMEN
Infection with hepadnaviruses and exposure to aflatoxin B1 (AFB1) are considered to be major risk factors in the development of hepatocellular carcinoma (HCC) in humans. A high rate of p53 mutations at codon 249 has been reported in these tumors. The tree shrew (Tupaia belangeri chinensis) is a useful animal model for the development of HCC after human hepatitis B virus (HBV) infection or AFB1 treatment. Therefore, it was of particular interest to determine whether the p53 gene in tree shrew HCCs associated with HBV infection and/or with exposure to AFB1 is affected in the same manner as in human HCCs. We determined the tree shrew p53 wild-type nucleotide sequences by RT-PCR and automatic DNA-sequencing. Tree shrew wild-type p53 sequence showed 91.7 and 93.4% homologies with human p53 nucleotide and amino acids sequences, respectively, while it showed 77.2 and 73.7% homologies in mice. One HCC and normal liver tissue from AFB1 treated and one HCC from AFB1- and HBV-treated tree shrew showed no change in p53 sequences, while three HCCs from AFB1- and HBV-treated tree shrews showed point mutations in p53 sequences. One HCC showed point mutations at codon 275, which is on the DNA-binding domain of p53 gene, which might be a cause of gain-of-function during the development of HCC. As a result, our finding indicates that tree shrews exposed to AFB1 and/or HBV had neither codon 249 mutations nor significant levels of other mutations in the p53 gene, as is the case with humans.
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Aflatoxina B1/toxicidad , Carcinoma Hepatocelular/genética , Hepatitis B/virología , Neoplasias Hepáticas/genética , Proteína p53 Supresora de Tumor/genética , Tupaiidae/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/virología , Clonación Molecular , Análisis Mutacional de ADN , ADN Complementario/química , ADN Complementario/genética , Modelos Animales de Enfermedad , Genes Supresores de Tumor/genética , Virus de la Hepatitis B , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/virología , Datos de Secuencia Molecular , Mutación , Mutación Puntual , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
The purpose of this paper was to study the mechanism of synergistic effect in hepatocarcinogenesis induced by hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) intake. Immunohistochemical staining was used in formalin-fixed, paraffin-embedded sections of cancer and liver tissues. The incidence of hepatocellular carcinomas (HCCs) was 52.9% in experimental tree shrews that received both HBV and AFB1. It was significantly higher than that of animals exposed to HBV (11.1%, Group B), or (AFB1) (15.8%, group C) alone. HCC was not found in the control animals (group D). The expressions of insulin-like growth factor II (IGF-II) were 82.4%, 22.2%, 26.3% and 0 in groups A, B, C and D, respectively. The significant differences of IGF-II were observed between groups A and B, C and D (P < 0.05). The expressions of p21 were 29.4%, 11.1%, 15.8% and 0 in group A, B, C and D, respectively. The positive rate of hepatitis B x antigen (HbxAg) was significantly higher in the group A than that in the group B (52.9% vs. 11.1%, P < 0.05). The parallel relations between the incidence of HCC and the overexpressions of these genes protein have been found in each group. On the other hand, the expressions of these genes in tumour-bearing tree shrews were significantly higher than that in nontumour-bearing animals. These findings suggest a synergistic effects of HBV and AFB1 in activation of these genes in tree shrews. Overexpressions of these genes may take an important role in the course of hepatocarcinogenesis in tree shrews.
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Antígenos de la Hepatitis B/análisis , Factor II del Crecimiento Similar a la Insulina/metabolismo , Neoplasias Hepáticas Experimentales/metabolismo , Proteína Oncogénica p21(ras)/metabolismo , Transactivadores/análisis , Aflatoxina B1/toxicidad , Animales , Cocarcinogénesis , Hepatitis B/complicaciones , Inmunohistoquímica , Técnicas In Vitro , Neoplasias Hepáticas Experimentales/etiología , Neoplasias Hepáticas Experimentales/virología , Tupaiidae , Proteínas Reguladoras y Accesorias ViralesRESUMEN
An animal experiment with tree shrews was performed to detect the synergistic effects of hepatitis B virus (HBV) infection and dietary aflatoxin B1 (AFB1) in hepatocarcinogenesis. Adult healthy tree shrews (Tupaia belangeri chinensis) were divided into four groups: Group A (HBV + AFB1)--animals were infected with human HBV serum at first, then fed AFB1 diluted with milk, 150 ug/kg.bw/day, 6 days/week for 105 weeks. Group B (HBV)--animals were infected with human HBV as Group A, but no AFB1 treatment. Group C (AFB1)--animals were treated with AFB1 as Group A but no HBV infection. Group D--animals were treated neither with human HBV nor AFB1. During the experiment, blood samples and liver biopsies were taken regularly from all animals in each group. All the animals were sacrificed on the 160th week when the experiment ended. The samples of sera and liver tissues were checked for HBV markers and histological changes. Hepatocellular carcinomas (HCCs) were found only in Group A and Group C, with incidences of 67% and 30% respectively. The average time for HCC occurrence in Group A and Group C was 120.3 +/- 16.6 and 153.3 +/- 5.8 weeks respectively (P < 0.01). Even though no HCC occurred in Group B, 1 animal which died before the end of the experiment showed two large hepatocellular nodules. These results showed that there is synergistic effect between HBV and AFB1 in tree shrews' hepatocarcinogenesis, even though the hepatocarcinogenic effect played by HBV alone is rather weak.
Asunto(s)
Aflatoxina B1/toxicidad , Cocarcinogénesis , Hepatitis B/complicaciones , Neoplasias Hepáticas Experimentales/etiología , Animales , Femenino , Hígado/patología , Neoplasias Hepáticas Experimentales/patología , Masculino , TupaiidaeRESUMEN
On the basis of the successful establishment of an animal model in tree shrews experimentally infected with human hepatitis B virus (HBV), a study on the hepatocarcinogenic effects of HBV and/or aflatoxin B1 (AFB1) was conducted. The results showed that the incidence of hepatocellular carcinoma (HCC) was significantly higher in the animals both infected with HBV and exposed to AFB1 (52.94%) than in those solely infected with HBV (11.11%) or exposed to AFB1 (12.50%). No HCC of precancerous lesions were found in the controls that were neither HBV-infected nor AFB-1 exposed. Precancerous lesions, including liver cell dysplasia and enzyme-altered hyperplastic hepatocyte foci, were observed before the occurrence of HCC, and the frequency of their appearance correlated well with the incidence of HCC. HBV DNA and the protein it encodes were detected in the cancer cells and/or the surrounding hepatocytes. Integration of HBV DNA into the host liver genome was found during hepatocarcinogenesis among the animals infected by HBV. These results suggest that exposure to HBV and AFB1 may play a synergistic role in the development of HCC, and support the viewpoint of an aetiological relationship between HBV and HCC.