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1.
J Nanobiotechnology ; 22(1): 355, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38902678

RESUMEN

BACKGROUND: Cancer recurrence following surgical resection is a major cause of treatment failure. Finding effective methods to prevent postoperative recurrence and wound infection is an important component of successful surgery. With the development of new nanotechnology, more treatment options have been provided for postoperative adjuvant therapy. This study presents an innovative hydrogel system that stimulates tumoricidal immunity after surgical resection of non-small cell lung cancer (NSCLC) and prevents cancer relapse. RESULTS: The hydrogel system is based on the excellent photothermal conversion performance of single-atom platinum (CN-Pt) along with the delivery and release of the chemotherapy drug, gemcitabine (GEM). The system is coated onto the wound surface after tumor removal with subsequent near-infrared (NIR) photothermal therapy, which efficiently induces necroptosis of residual cancer cells, amplifies the levels of damage-associated molecular patterns (DAMPs), and increases the number of M1 macrophages. The significantly higher levels of phagocytic macrophages enhance tumor immunogenicity and sensitize cancer cells to CD8 + T-cell immunity to control postoperative recurrence, which has been verified using an animal model of postoperative lung cancer recurrence. The CN-Pt-GEM-hydrogel with NIR can also inhibit postoperative wound infection. CONCLUSIONS: These findings introduce an alternative strategy for supplementing antitumor immunity in patients undergoing resection of NSCLC tumors. The CN-Pt-GEM-hydrogel with the NIR system also exhibits good biosafety and may be adaptable for clinical application in relation to tumor resection surgery, wound tissue filling, infection prevention, and recurrence prevention.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Desoxicitidina , Gemcitabina , Hidrogeles , Neoplasias Pulmonares , Necroptosis , Animales , Ratones , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Hidrogeles/química , Humanos , Necroptosis/efectos de los fármacos , Recurrencia Local de Neoplasia , Línea Celular Tumoral , Inmunoterapia/métodos , Terapia Fototérmica/métodos , Infección de Heridas/prevención & control , Infección de Heridas/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos
2.
World J Clin Cases ; 11(23): 5519-5524, 2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37637687

RESUMEN

BACKGROUND: Total hip arthroplasty (THA) is an effective treatment for advanced osteonecrosis of the femoral head, which can significantly relieve pain and improve patients' quality of life. Robotic-assisted THA enhances the accuracy and stability of THA surgery and achieves better clinical outcomes than manual THA. CASE SUMMARY: We report the clinical outcomes of robotic-assisted THA and manual THA in the same patient with osteonecrosis of the femoral head. A 49-year-old male patient attended our hospital due to more than 3 years of pain in both hip joints. The left hip was treated with robotic-assisted THA. The patient underwent manual THA of the right hip 3 mo after robotic-assisted THA. We obtained postoperative radiograph parameters, Harris hip score and forgotten joint score of the patient 1 year after surgery. CONCLUSION: Compared with manual THA, the patient's left hip felt better 1 year after robotic-assisted THA. Robotic-assisted THA resulted in a better Harris hip score and forgotten joint score than manual THA in the same patient with osteonecrosis of the femoral head.

3.
Bioeng Transl Med ; 8(4): e10430, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37476070

RESUMEN

Although immunotherapy has improved the clinical treatment of lung adenocarcinoma (LUAD), many tumors have poor responses to immunotherapy. In this study, we confirmed that high expression of Cyclin-Dependent Kinase 7 (CDK7) promoted an immunosuppressive macrophage phenotype and macrophage infiltration in LUAD. Thus, we have developed an internalizing-RGD (iRGD)-conjugated gold nanoparticle (AuNP) system which carries siCDK7 to activate the antitumor immune response. The iRGD-conjugated AuNP/siCDK7 system exhibited good tumor targeting performance and photothermal effects. The AuNP/siCDK7 system with excellent biosafety exerted a significant photothermal antitumor effect by inducing tumor cell necroptosis. Furthermore, the AuNP/siCDK7 system ameliorated the immunosuppressive microenvironment and enhanced the efficacy of anti-PD-1 treatment by increasing CD8+ T cell infiltration and decreasing M2 macrophage infiltration. Hence, this iRGD-conjugated AuNP/siCDK7 system is a potential treatment strategy for lung adenocarcinoma, which exerts its effects by triggering tumor cell necroptosis and immunotherapeutic responses.

4.
Cancers (Basel) ; 13(22)2021 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-34831010

RESUMEN

Tissue extracellular matrix (ECM) is a structurally and compositionally unique microenvironment within which native cells can perform their natural biological activities. Cells grown on artificial substrata differ biologically and phenotypically from those grown within their native tissue microenvironment. Studies examining human tissue ECM structures and the biology of human tissue cells in their corresponding tissue ECM are lacking. Such investigations will improve our understanding about human pathophysiological conditions for better clinical care. We report here human normal breast tissue and invasive ductal carcinoma tissue ECM structural features. For the first time, a hydrogel was successfully fabricated using whole protein extracts of human normal breast ECM. Using immunofluorescence staining of type I collagen (Col I) and machine learning of its fibrous patterns in the polymerized human breast ECM hydrogel, we have defined the microstructural characteristics of the hydrogel and compared the microstructures with those of other native ECM hydrogels. Importantly, the ECM hydrogel supported 3D growth and cell-ECM interaction of both normal and cancerous mammary epithelial cells. This work represents further advancement toward full reconstitution of the human breast tissue microenvironment, an accomplishment that will accelerate the use of human pathophysiological tissue-derived matrices for individualized biomedical research and therapeutic development.

5.
Braz. j. med. biol. res ; 54(9): e10842, 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1249339

RESUMEN

Regeneration of injured peripheral nerves is an extremely complex process. Nogo-A (neurite outgrowth inhibitor-A) inhibits axonal regeneration by interacting with Nogo receptor in the myelin sheath of the central nervous system (CNS). The aim of this study was to investigate the effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats. Sprague-Dawley rats (n=96) were randomly divided into 4 groups: control group (control), sciatic nerve transection group (model), immediate repair group (immediate repair), and delayed repair group (delayed repair). The rats were euthanized 1 week and 6 weeks after operation. The injured end tissues of the spinal cord and sciatic nerve were obtained. The protein expressions of Nogo-A and Nogo-66 receptor (NgR) were detected by immunohistochemistry. The protein expressions of Nogo-A, NgR, and Ras homolog family member A (RhoA) were detected by western blot. At 1 week after operation, the pathological changes in the immediate repaired group were less, and the protein expressions of Nogo-A, NgR, and RhoA in the spinal cord and sciatic nerve tissues were decreased (P<0.05) compared with the model group. After 6 weeks, the pathological changes in the immediate repair group and the delayed repair group were alleviated and the protein expressions decreased (P<0.05). The situation of the immediate repair group was better than that of the delayed repair group. Our data suggest that the expression of Nogo-A and its receptor increased after sciatic nerve injury, indicating that Nogo-A and its receptor play an inhibitory role in the repair process of sciatic nerve injury in rats.


Asunto(s)
Animales , Ratas , Receptores de Superficie Celular , Proteínas de la Mielina , Nervio Ciático , Ratas Sprague-Dawley , Proteínas Ligadas a GPI , Proteínas Nogo , Regeneración Nerviosa
6.
Materials (Basel) ; 11(5)2018 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-29883394

RESUMEN

In order to predict flow behavior and find the optimum hot working processing parameters for 5754 aluminum alloy, the experimental flow stress data obtained from the isothermal hot compression tests on a Gleeble-3500 thermo-simulation apparatus, with different strain rates (0.1⁻10 s⁻1) and temperatures (300⁻500 °C), were used to construct the constitutive models of the strain-compensation Arrhenius (SA) and back propagation (BP) artificial neural network (ANN). In addition, an optimized BP⁻ANN model based on the genetic algorithm (GA) was established. Furthermore, the predictability of the three models was evaluated by the statistical indicators, including the correlation coefficient (R) and average absolute relative error (AARE). The results showed that the R of the SA model, BP⁻ANN model, and ANN⁻GA model were 0.9918, 0.9929, and 0.9999, respectively, while the AARE of these models was found to be 3.2499⁻5.6774%, 0.0567⁻5.4436% and 0.0232⁻1.0485%, respectively. The prediction error of the SA model was high at 400 °C. It was more accurate to use the BP⁻ANN model to determine the flow behavior compared to the SA model. However, the BP⁻ANN model had more instability at 300 °C and a true strain in the range of 0.4⁻0.6. When compared with the SA model and BP⁻ANN model, the ANN⁻GA model had a more efficient and more accurate prediction ability during the whole deformation process. Furthermore, the dynamic softening characteristic was analyzed by the flow curves. All curves showed that 5754 aluminum alloy showed the typical rheological characteristics. The flow stress rose rapidly with increasing strain until it reached a peak. After this, the flow stress remained constant, which demonstrates a steady flow softening phenomenon. Besides, the flow stress and the required variables to reach the steady state deformation increased with increasing strain rate and decreasing temperature.

7.
Theor Appl Genet ; 131(6): 1273-1285, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29478186

RESUMEN

KEY MESSAGE: We report a repertoire of diverse aneuploids harbored by a newly synthesized segmental allotetraploid rice population with fully sequenced sub-genomes and demonstrate their retention features and phenotypic consequences. Aneuploidy, defined as unequal numbers of different chromosomes, is a large-effect genetic variant and may produce diverse cellular and organismal phenotypes. Polyploids are more permissive to chromosomal content imbalance than their diploid and haploid counterparts, and therefore, may enable more in-depth investigation of the phenotypic consequences of aneuploidy. Based on whole-genome resequencing, we identify that ca. 40% of the 312 selfed individual plants sampled from an early generation rice segmental allotetraploid population are constitutive aneuploids harboring 55 distinct aneuploid karyotypes. We document that gain of a chromosome is more prevalent than loss of a chromosome, and the 12 rice chromosomes have distinct tendencies to be in an aneuploid state. These properties of aneuploidy are constrained by multiple factors including the number of genes residing on the chromosome and predicted functional connectivity with other chromosomes. Two broad categories of aneuploidy-associated phenotypes are recognized: those shared by different aneuploids, and those associated with aneuploidy of a specific chromosome. A repertoire of diverse aneuploids in the context of a segmental allotetraploid rice genome with fully sequenced sub-genomes provides a tractable resource to explore the roles of aneuploidy in nascent polyploid genome evolution and helps to decipher the mechanisms conferring karyotypic stabilization on the path to polyploid speciation and towards artificial construction of novel polyploid crops.


Asunto(s)
Aneuploidia , Oryza/genética , Fitomejoramiento , Poliploidía , Genoma de Planta , Cariotipo , Fenotipo
8.
Vet Surg ; 45(2): 261-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26768085

RESUMEN

OBJECTIVE: To determine a long term function of tibial tuberosity advancement (TTA) for treatment of ruptured cranial cruciate ligament (CCL) in dogs, and to compare this to the long term function of previously reported tibial plateau leveling osteotomy (TPLO), extracapsular reconstruction (ECR), and a population of normal dogs. STUDY DESIGN: Prospective clinical trial. ANIMALS: Dogs with unilateral ruptured CCL treated with TTA (n = 14), TPLO (n = 15), and ECR (n = 23), and normal adult dogs (control, n = 80). MATERIALS AND METHODS: Force plate gait analysis was performed at 1 time point for the normal control group and preoperatively, and at 2 and 8 weeks and 6 and 12 months postoperatively for the treatment groups. Using serial force plates, symmetry indices (SI) were calculated between the operated and unoperated pelvic limbs for peak vertical force (PVF), contact time (CT), and vertical impulse (VI). Ground reaction forces (GRF) of the treatment and control group were compared using a general linear model. RESULTS: Walk SI for dogs with TTA were not significantly different from the control group at 12 months postoperatively. At the trot, neither TTA nor ECR achieved normal GRF. SI of the TPLO group were not different from the normal control group by 6-12 months postoperatively. CONCLUSION: At the walk, TTA achieves normal function by 12 months; however, at the trot TTA is indistinguishable from ECR. TPLO resulted in operated limb function that was similar to the control population by 6-12 months postoperatively at the walk and the trot.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Perros/lesiones , Tibia/cirugía , Animales , Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/veterinaria , Perros/cirugía , Femenino , Masculino , Osteotomía/veterinaria , Estudios Prospectivos , Recuperación de la Función
9.
BMC Genomics ; 16: 598, 2015 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-26268218

RESUMEN

BACKGROUND: Soybean cyst nematode (SCN, Heterodera glycines Ichinohe) is one of the most fatal pests of soybean (Glycine max (L.) Merr.) worldwide and causes huge loss of soybean yield each year. Multiple sources of resistance are urgently needed for effective management of SCN via the development of resistant cultivars. The aim of the present study was to investigate the genetic architecture of resistance to SCN HG Type 0 (race 3) and HG Type 1.2.3.5.7 (race 4) in landraces and released elite soybean cultivars mostly from China. RESULTS: A total of 440 diverse soybean landraces and elite cultivars were screened for resistance to SCN HG Type 0 and HG Type 1.2.3.5.7. Exactly 131 new sources of SCN resistance were identified. Lines were genotyped by SNP markers detected by the Specific Locus Amplified Fragment Sequencing (SLAF-seq) approach. A total of 36,976 SNPs were identified with minor allele frequencies (MAF) > 4% that were present in 97% of all the genotypes. Genome-wide association mapping showed that a total of 19 association signals were significantly related to the resistance for the two HG Types. Of the 19 association signals, eight signals overlapped with reported QTL including Rhg1 and Rhg4 genes. Another eight were located in the linked regions encompassing known QTL. Three QTL were found that were not previously reported. The average value of female index (FI) of soybean accessions with resistant alleles was significantly lower than those with susceptible alleles for each peak SNP. Disease resistance proteins with leucine rich regions, cytochrome P450s, protein kinases, zinc finger domain proteins, RING domain proteins, MYB and WRKY transcription activation families were identified. Such proteins may participate in the resistant reaction to SCN and were frequently found in the tightly linked genomic regions of the peak SNPs. CONCLUSIONS: GWAS extended understanding of the genetic architecture of SCN resistance in multiple genetic backgrounds. Nineteen association signals were obtained for the resistance to the two Hg Types of SCN. The multiple beneficial alleles from resistant germplasm sources will be useful for the breeding of cultivars with improved resistance to SCN. Analysis of genes near association signals may facilitate the recognition of the causal gene(s) underlying SCN resistances.


Asunto(s)
Mapeo Cromosómico/métodos , Resistencia a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , Glycine max/genética , Animales , Genes de Plantas , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Glycine max/parasitología , Tylenchoidea/genética , Tylenchoidea/fisiología
10.
PLoS One ; 9(1): e87438, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24498106

RESUMEN

Root damage caused by aluminum (Al) toxicity is a major cause of grain yield reduction on acid soils, which are prevalent in tropical and subtropical regions of the world where food security is most tenuous. In sorghum, Al tolerance is conferred by SbMATE, an Al-activated root citrate efflux transporter that underlies the major Al tolerance locus, AltSB, on sorghum chromosome 3. We used association mapping to gain insights into the origin and evolution of Al tolerance in sorghum and to detect functional variants amenable to allele mining applications. Linkage disequilibrium across the AltSB locus decreased much faster than in previous reports in sorghum, and reached basal levels at approximately 1000 bp. Accordingly, intra-locus recombination events were found to be extensive. SNPs and indels highly associated with Al tolerance showed a narrow frequency range, between 0.06 and 0.1, suggesting a rather recent origin of Al tolerance mutations within AltSB. A haplotype network analysis suggested a single geographic and racial origin of causative mutations in primordial guinea domesticates in West Africa. Al tolerance assessment in accessions harboring recombinant haplotypes suggests that causative polymorphisms are localized to a ∼6 kb region including intronic polymorphisms and a transposon (MITE) insertion, whose size variation has been shown to be positively correlated with Al tolerance. The SNP with the strongest association signal, located in the second SbMATE intron, recovers 9 of the 14 highly Al tolerant accessions and 80% of all the Al tolerant and intermediately tolerant accessions in the association panel. Our results also demonstrate the pivotal importance of knowledge on the origin and evolution of Al tolerance mutations in molecular breeding applications. Allele mining strategies based on associated loci are expected to lead to the efficient identification, in diverse sorghum germplasm, of Al tolerant accessions able maintain grain yields under Al toxicity.


Asunto(s)
Aluminio/efectos adversos , Proteínas Portadoras/genética , Tolerancia a Medicamentos/genética , Sitios Genéticos/genética , Sorghum/genética , África Occidental , Alelos , Mapeo Cromosómico/métodos , Grano Comestible/genética , Haplotipos , Intrones/genética , Desequilibrio de Ligamiento/genética , Mutación/genética , Raíces de Plantas/genética , Polimorfismo de Nucleótido Simple/genética
11.
PLoS One ; 8(10): e76390, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24124555

RESUMEN

Hip (HD) and Elbow Dysplasia (ED) are two common complex developmental disorders of dogs. In order to decrease their prevalence and severity, the Orthopedic Foundation for Animals (OFA) has a voluntary registry of canine hip and elbow conformation certified by boarded radiologists. However, the voluntarily reports have been severely biased against exposing dogs with problems, especially at beginning period. Fluctuated by additional influential factors such as age, the published raw scores barely showed trends of improvement. In this study, we used multiple-trait mixed model to simultaneously adjust these factors and incorporate pedigree to derive Estimated Breeding Values (EBV). A total of 1,264,422 dogs from 74 breeds were evaluated for EBVs from 760,455 hip scores and 135,409 elbow scores. These EBVs have substantially recovered the reporting bias and the other influences. Clear and steady trends of genetic improvement were observed over the 40 years since 1970. The total genetic improvements were 16.4% and 1.1% of the phenotypic standard deviation for HD and ED, respectively. The incidences of dysplasia were 0.83% and 2.08%, and the heritabilities were estimated as 0.22 and 0.17 for hip and elbow scores, respectively. The genetic correlation between them was 0.12. We conclude that EBV is more effective than reporting raw phenotype. The weak genetic correlation suggested that selection based on hip scores would also slightly improve elbow scores but it is necessary to allocate effort toward improvement of elbow scores alone.


Asunto(s)
Articulación del Codo/metabolismo , Articulación del Codo/patología , Displasia Pélvica Canina/epidemiología , Displasia Pélvica Canina/genética , Luxaciones Articulares/congénito , Factores de Edad , Animales , Cruzamiento , Perros , Femenino , Masculino , Fenotipo , Factores Sexuales
12.
Vet Surg ; 42(1): 38-50, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23153073

RESUMEN

OBJECTIVE: To compare the long-term outcome of tibial plateau leveling osteotomy (TPLO) and extracapsular repair (ECR) for treatment of a ruptured cranial cruciate ligament (RCCL). STUDY DESIGN: Prospective clinical trial. ANIMALS: Normal adult dogs (control, n = 79); dogs with unilateral CCL disease (n = 38). METHODS: Dogs had TPLO (n = 15) or ECR (n = 23) for treatment of RCCL. Force plate gait analysis was performed for the control group at one time point and for treatment groups at serial points: preoperatively, 2 weeks, 8 weeks, 6 and 12 months postoperatively. Symmetry indices (SIs) were calculated between operated and unoperated pelvic limb for ground reaction forces (GRFs), including peak vertical force (PVF), contact time (CT), and vertical impulse (VI). GRFs of the treatment groups and control group were compared using a general linear model and Kaplan-Meier survival analysis. RESULTS: At 8 weeks, for PVF and VI, the TPLO group had more symmetric limb loading than the ECR group at the walk and trot. SIs of the TPLO group were not different from the control group by 6 months to 1 year postoperatively. SIs for the ECR group were less symmetrical than the control group at all time periods. Using survival analysis, median time to normal function was no different at the walk between groups, but was shorter for the TPLO group for VI and PVF. CONCLUSIONS: Dogs achieved normal limb loading faster after TPLO than ECR. TPLO resulted in operated limb function that was indistinguishable from the control population by 1 year postoperatively.


Asunto(s)
Enfermedades de los Perros/cirugía , Osteotomía/veterinaria , Tibia/cirugía , Animales , Perros , Femenino , Masculino , Factores de Tiempo
13.
Vet Surg ; 41(8): 966-72, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23198923

RESUMEN

OBJECTIVE: To determine if medial patellar luxation (MPL) in Yorkshire Terriers is associated with tibial torsion. STUDY DESIGN: Prospective cross-sectional study. ANIMALS: Yorkshire Terriers (n = 30; 60 tibiae). METHODS: Each MPL was graded using a categorical grading scheme. Computed tomography of the tibiae was performed and tibial torsion angle (TTA) was assessed. MPL grade was analyzed with a general linear model where the independent variables include sex, neutering status, age, weight, and TTA. RESULTS: Factors that had collective impact on MPL grade were TTA, age, and weight squared. As MPL grade increased, TTA decreased by 0.05° and age increased by 0.13 years. As weight increased, MPL decreased. There was no effect (P > .05) from scorers, side, and neutering status. CONCLUSION: Body weight squared, TTA, and age affect MPL grade, suggesting that a torsional deformity may contribute to the development of MPL in Yorkshire terriers along with weight and age.


Asunto(s)
Luxación de la Rótula/veterinaria , Animales , Estudios Transversales , Enfermedades de los Perros/congénito , Enfermedades de los Perros/epidemiología , Perros , Femenino , Masculino , Luxación de la Rótula/complicaciones , Tibia/patología , Tomografía Computarizada por Rayos X , Anomalía Torsional/veterinaria
14.
Am J Vet Res ; 72(4): 530-40, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21453155

RESUMEN

OBJECTIVE: To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs. ANIMALS: 1,551 dogs. Procedures-Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever-Greyhound crossbreeds. RESULTS: The Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage. CONCLUSIONS AND CLINICAL RELEVANCE: The FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.


Asunto(s)
Enfermedades de los Perros/genética , Displasia Pélvica Canina/genética , Proteínas de Microfilamentos/genética , Osteoartritis/veterinaria , Animales , Enfermedades de los Perros/diagnóstico por imagen , Perros/genética , Perros/fisiología , Femenino , Fibrilinas , Predisposición Genética a la Enfermedad , Haplotipos , Displasia Pélvica Canina/diagnóstico por imagen , Masculino , Proteínas de Microfilamentos/fisiología , Mutación , Osteoartritis/diagnóstico por imagen , Osteoartritis/genética , ARN Mensajero/genética , Radiografía
15.
PLoS One ; 5(10): e13219, 2010 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-20949002

RESUMEN

BACKGROUND: Canine hip dysplasia (HD) is a common polygenic trait characterized by hip malformation that results in osteoarthritis (OA). The condition in dogs is very similar to developmental dysplasia of the human hip which also leads to OA. METHODOLOGY/PRINCIPAL FINDINGS: A total of 721 dogs, including both an association and linkage population, were genotyped. The association population included 8 pure breeds (Labrador retriever, Greyhounds, German Shepherd, Newfoundland, Golden retriever, Rottweiler, Border Collie and Bernese Mountain Dog). The linkage population included Labrador retrievers, Greyhounds, and their crosses. Of these, 366 dogs were genotyped at ∼22,000 single nucleotide polymorphism (SNP) loci and a targeted screen across 8 chromosomes with ∼3,300 SNPs was performed on 551 dogs (196 dogs were common to both sets). A mixed linear model approach was used to perform an association study on this combined association and linkage population. The study identified 4 susceptibility SNPs associated with HD and 2 SNPs associated with hip OA. CONCLUSION/SIGNIFICANCE: The identified SNPs included those near known genes (PTPRD, PARD3B, and COL15A1) reported to be associated with, or expressed in, OA in humans. This suggested that the canine model could provide a unique opportunity to identify genes underlying natural HD and hip OA, which are common and debilitating conditions in both dogs and humans.


Asunto(s)
Enfermedades del Desarrollo Óseo/veterinaria , Enfermedades de los Perros/genética , Articulación de la Cadera/patología , Osteoartritis/genética , Animales , Enfermedades del Desarrollo Óseo/genética , Mapeo Cromosómico , Perros , Ligamiento Genético , Polimorfismo de Nucleótido Simple
16.
Chem Pharm Bull (Tokyo) ; 58(7): 983-5, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20606352

RESUMEN

Pollenopyrroside A and pollenopyrroside B, novel pyrrole ketohexoside derivatives, were isolated from the extract of Bee-collected Brassica campestris pollen. Their structures were elucidated by spectroscopic analysis (UV, IR, MS, NMR and X-ray) and chemical evidence. Pollenopyrrosides A and B represent a novel carbon skeleton with a six-six and five-six member dioxaspirocycle bearing nitrogen atom, respectively.


Asunto(s)
Antineoplásicos Fitogénicos/química , Brassica/química , Polen/química , Pirroles/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/toxicidad , Abejas , Línea Celular Tumoral , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Pirroles/aislamiento & purificación , Pirroles/toxicidad
17.
PLoS One ; 5(2): e9410, 2010 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-20195372

RESUMEN

BACKGROUND: Canine Hip Dysplasia (CHD) is a common inherited disease that affects dog wellbeing and causes a heavy financial and emotional burden to dog owners and breeders due to secondary hip osteoarthritis. The Orthopedic Foundation for Animals (OFA) initiated a program in the 1960's to radiograph hip and elbow joints and release the OFA scores to the public for breeding dogs against CHD. Over last four decades, more than one million radiographic scores have been released. METHODOLOGY/PRINCIPAL FINDINGS: The pedigrees in the OFA database consisted of 258,851 Labrador retrievers, the major breed scored by the OFA (25% of total records). Of these, 154,352 dogs had an OFA hip score reported between 1970 and 2007. The rest of the dogs (104,499) were the ancestors of the 154,352 dogs to link the pedigree relationships. The OFA hip score is based on a 7-point scale with the best ranked as 1 (excellent) and the worst hip dysplasia as 7. A mixed linear model was used to estimate the effects of age, sex, and test year period and to predict the breeding value for each dog. Additive genetic and residual variances were estimated using the average information restricted maximum likelihood procedure. The analysis also provided an inbreeding coefficient for each dog. The hip scores averaged 1.93 (+/-SD = 0.59) and the heritability was 0.21. A steady genetic improvement has accrued over the four decades. The breeding values decreased (improved) linearly. By the end of 2005, the total genetic improvement was 0.1 units, which is equivalent to 17% of the total phenotypic standard deviation. CONCLUSION/SIGNIFICANCE: A steady genetic improvement has been achieved through the selection based on the raw phenotype released by the OFA. As the heritability of the hip score was on the low end (0.21) of reported ranges, we propose that selection based on breeding values will result in more rapid genetic improvement than breeding based on phenotypic selection alone.


Asunto(s)
Cruzamiento/métodos , Perros/genética , Displasia Pélvica Canina/genética , Articulación de la Cadera/patología , Animales , Femenino , Articulación de la Cadera/diagnóstico por imagen , Endogamia , Masculino , Ortopedia/métodos , Ortopedia/estadística & datos numéricos , Ortopedia/veterinaria , Linaje , Fenotipo , Radiografía , Estudios Retrospectivos , Factores de Tiempo , Estados Unidos
18.
Am J Vet Res ; 70(4): 483-92, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19335104

RESUMEN

OBJECTIVE-To estimate heritabilities and genetic correlations among 4 traits of hip joints (distraction index [DI], dorsolateral subluxation [DLS] score, Norberg angle [NA], and extended-hip joint radiograph [EHR] score) and to derive the breeding values for these traits in dogs. ANIMALS-2,716 dogs of 17 breeds (1,551 dogs in which at least 1 hip joint trait was measured). PROCEDURES-The NA was measured, and an EHR score was assigned. Hip joint radiographs were obtained from some dogs to allow calculation of the DI and DLS score. Heritabilities, genetic correlations, and breeding values among the DI, DLS score, NA, and EHR score were calculated by use of a set of multiple-trait, derivative-free, restricted maximum likelihood computer programs. RESULTS-Among 2,716 dogs, 1,411 (52%) had an estimated inbreeding coefficient of 0%; the remaining dogs had a mean inbreeding coefficient of 6.21%. Estimated heritabilities were 0.61, 0.54, 0.73, and 0.76 for the DI, DLS score, NA, and EHR score, respectively. The EHR score was highly genetically correlated with the NA (r = -0.89) and was moderately genetically correlated with the DI (r = 0.69) and DLS score (r = -0.70). The NA was moderately genetically correlated with the DI (r = -0.69) and DLS score (r = 0.58). Genetic correlation between the DI and DLS score was high (r = -0.91). CONCLUSIONS AND CLINICAL RELEVANCE-Establishment of a selection index that makes use of breeding values jointly estimated from the DI, DLS score, NA, and EHR score should enhance breeding programs to reduce the incidence of hip dysplasia in dogs.


Asunto(s)
Cruzamiento , Predisposición Genética a la Enfermedad , Herencia/genética , Displasia Pélvica Canina/genética , Animales , Perros , Femenino , Articulación de la Cadera/patología , Masculino , Linaje , Índice de Severidad de la Enfermedad
19.
Vet J ; 181(2): 97-110, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19297220

RESUMEN

Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1-2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a 'breeding value' that could improve the accuracy of predicting a dog's hip conformation.


Asunto(s)
Displasia Pélvica Canina/genética , Polimorfismo de Nucleótido Simple , Animales , Cruzamiento , Mapeo Cromosómico , Perros/genética , Genotipo , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/patología , Repeticiones de Microsatélite , Fenotipo , Sitios de Carácter Cuantitativo , Radiografía
20.
Genomics ; 90(2): 276-84, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17531439

RESUMEN

Genetic imprinting may have played a more notable role in shaping embryonic development of plants, animals, and humans than previously appreciated. Quantitative trait loci that are imprinted (iQTL) exert monoallelic effects, depending on the parent of origin, which is an exception to the laws of Mendelian genetics. In this article, we present a modified random effect-based mapping model to use in a genome-wide scan for the distribution of iQTL that contribute to genetic variance for a complex trait in a structured pedigree. This model, implemented with the maximum likelihood method, capitalizes on a network of relatedness for maternally and paternally derived alleles through identical-by-descent sharing, thus allowing for the discrimination of the genetic variances due to alleles derived from maternal and paternal parents. The model was employed to map iQTL responsible for canine hip dysplasia in a multihierarchical canine pedigree, founded with seven greyhounds and six Labrador retrievers. Of eight significant QTL detected, three, located on CFA1, CFA8, and CF28, were found to trigger significant parent-of-origin effects on the age of femoral capital ossification measured at the left and right hips of a canine. The detected iQTL provide important candidate regions for fine-mapping of imprinted genes and for studying their structure and function in the control of complex traits.


Asunto(s)
Impresión Genómica , Displasia Pélvica Canina/genética , Modelos Estadísticos , Sitios de Carácter Cuantitativo , Animales , Perros , Ligamiento Genético , Linaje
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