RESUMEN
Kawasaki disease (KD) is a systemic inflammatory vascular disorder that predominantly affects children and is the leading cause of acquired heart disease in children. Although the etiology of this disease remains unclear, genome-wide association and genome-wide linkage studies have shown that some susceptible genes and chromosomal regions are associated with the development and progression of KD. With the advancement of high-throughput DNA sequencing techniques, more and more genomic information related to KD is being discovered. Understanding the genes involved in the pathogenesis of KD may provide novel insights into the diagnosis and treatment of KD. By analyzing related articles and summarizing related research advances, this article mainly discusses the T cell activation-enhancing genes that have been confirmed to be closely associated with the development and progression of KD and reveals their association with the pathogenesis of KD and coronary artery lesions.
Asunto(s)
Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Síndrome Mucocutáneo Linfonodular/complicaciones , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Vasos Coronarios/patología , Polimorfismo de Nucleótido SimpleRESUMEN
TEOSINTE BRANCHED 1/CYCLOIDEA/PCF (TCP) transcription factors play crucial roles in plant abiotic stresses. However, little is known about the role of TCP genes in the drought stress tolerance of apple. Here, we found that abscisic acid (ABA) and drought treatment reduced the expression of MdTCP46, and overexpression of MdTCP46 reduced ABA sensitivity and drought stress resistance. MdTCP46 was found to interact with MdABI5 both in vitro and in vivo, and this interaction was essential for drought resistance via the ABA-dependent pathway. Overexpression of MdABI5 enhanced ABA sensitivity and drought stress resistance by directly activating the expression of MdEM6 and MdRD29A. MdTCP46 significantly suppressed the transcriptional activity of MdABI5, thereby negatively regulating MdABI5-mediated ABA signalling and drought response. Overall, our results demonstrate that the MdTCP46-MdABI5-MdEM6/MdRD29A regulatory module plays a key role in the modulation of ABA signalling and the drought stress response. These findings provide new insight into the role of MdTCP46 in ABA signalling and abiotic stress responses.
Asunto(s)
Arabidopsis , Malus , Ácido Abscísico/metabolismo , Arabidopsis/genética , Sequías , Regulación de la Expresión Génica de las Plantas , Malus/genética , Malus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Estrés Fisiológico/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
A time-economical and robust synthesis of various selenofunctionalized heterocycles was accomplished via I2O5-mediated selenocyclizations of olefins with diselenides. Using this method, 116 selenomethyl-substituted heterocycles were synthesized with up to 97% isolated yield in minutes. Additional features of this new protocol include the use of an inorganic oxidant, mild conditions, and easy operation. Preliminary investigations suggest that the transformation operates through selenenyl iodide-induced electrophilic cyclization.
RESUMEN
Adiponectin, also known as ADIPOQ, is a hormone protein secreted by adipocytes. The ADIPOQ gene is expressed primarily in adipose tissue, and the encoded protein circulates in the bloodstream and has the potential to regulate both animal fat metabolism and hormone production. Our previous work uncovered a 67-bp variable duplication in the promoter region of ADIPOQ, which reduced the basal transcriptional activity of ADIPOQ in the 3T3_L1 cell and also inhibits the ADIPOQ mRNA expression in adipose tissue. Accordingly, the present study aimed to identify the relationship between the 67-bp structural variations in ADIPOQ promoter region and the milk traits of Xinjiang brown cattle (XJBC). The results revealed two genotypes, DD and ID, in the XJBC, and minor allelic frequency (MAF) for the 'I' allele was more than 1%. Moreover, the association analysis revealed that the 67-bp duplication in the promoter region of the ADIPOQ gene was significantly correlated with the 305 days of milk production volume, fat yield, and milk fat percentage in the XJBC (p < 0.05). These results obtained in this study suggested that the identified variable duplication could be considered as the potential genetic marker for improving milk traits of XJBC.
Asunto(s)
Adiponectina , Leche , Bovinos/genética , Animales , Leche/metabolismo , Fenotipo , Genotipo , Adiponectina/genética , Adiponectina/metabolismo , Regiones Promotoras Genéticas/genéticaRESUMEN
1-naphthol (1-NAP) is the main metabolite of pesticide carbaryl and naphthalene, and is also a genotoxic and carcinogenic intermediate in the synthesis of organic compound, dyes, pigment and pharmaceutical industry. In this work, two novel haptens were designed and synthesized for developing a competitive indirect enzyme-linked immunosorbent assay (ciELISA) method for 1-NAP in urine samples. The assay showed a limit of detection of 2.21 ng/mL and working range from 4.02 ng/mL to 31.25 ng/mL for 1-NAP in optimized working buffer. The matrix effect of samples was eliminated via 15-fold dilution of optimized working buffer. Good average recoveries (102.4%-123.4%) with a coefficient of variation from 11.7% to 14.7% was obtained for spiked urine samples. Subsequent instrument verification test showed good correlation between the results of ciELISA and high-performance liquid chromatography. The developed ciELISA is a high-throughput tool to monitor 1-NAP in urine, which can provide technical support for the establishment of biological exposure level for the exposure to carbaryl, naphthalene and other related pollutants.
Asunto(s)
Anticuerpos Monoclonales/química , Ensayo de Inmunoadsorción Enzimática/métodos , Haptenos/química , Naftoles/orina , Residuos de Plaguicidas/orina , Anticuerpos Monoclonales/inmunología , Carbaril/metabolismo , Exposición a Riesgos Ambientales/análisis , Límite de Detección , Naftalenos/metabolismo , Naftoles/inmunología , Residuos de Plaguicidas/inmunología , Residuos de Plaguicidas/metabolismoRESUMEN
Xinjiang inbred cattle is a population which has been highly inbred for 45 years. However, the breed origin of this population cannot be traced back due to the lack of original records. To demonstrate the genetic background of Xinjiang inbred cattle, we analysed the worldwide genomic information of 16 cattle breeds using principal components analysis, and Admixture method. Furthermore, the shared SNP markers of Xinjiang inbred cattle, local Kazakh cattle, Holstein cattle, and Xinjiang Brown cattle were extracted to calculate population genetic parameters and genomic inbreeding indicators in order to evaluate the magnitude of inbreeding in each population. We also evaluated the relationship between inbreeding indicators and body size in the Xinjiang inbred population. Finally, the high frequency runs of homozygosity (ROH) regions for Xinjiang inbred cattle and local Kazakh population were selected for genes and QTL annotations. These results demonstrate that the ancestry proportions of inbreeding breed are similar to those of Kazakh cattle. The genomic homozygosity of Xinjiang inbred cattle is significantly higher than other populations; the inbreeding depression is observed in body size to a certain extent because body size decreased when corresponding homozygosity increased. Totally, six basic bio-pathways and 32 QTL regions that related to bovine economical traits were annotated. Our results provide the insights into breeding strategies, future protection, and utilization plan design for this special genetic material-Xinjiang inbred cattle.
Asunto(s)
Cruzamiento , Bovinos/genética , Homocigoto , Polimorfismo de Nucleótido Simple , Animales , Antecedentes Genéticos , Genómica , EndogamiaRESUMEN
Endometriosis is a chronic inflammatory syndrome and nearly 6%-10% of women are affected by it during the reproductive period. Previous studies have proved that microRNAs (miRNAs) are implicated in the pathogenesis of ovarian endometriosis. In this study, we aimed to investigate that restored miR-488 would effectively inhibit the development of endometriosis. The microarray-based data analysis was performed to screen endometriosis-related differentially expressed genes (DEGs). The mouse model in endometriosis syndrome was established by being subcutaneously injected with Estradiol benzoate, and the ectopic endometrial tissues and normal endometrial tissues were collected. Additionally, the endometrial glandular epithelial cells were extracted from the endometrial glandular epithelial tissues from normal and endometriosis mice. In order to examine the role of miR-488 in mice with endometriosis, we measured miR-488 expression and expression levels of Frizzled-7 (FZD7), cyclinD1, ß-catenin, and c-Myc in vivo and in vitro. Finally, we detected the effect of miR-488 on cell proliferation, apoptosis, migration and invasion in vitro. FZD7 was upregulated in human endometriosis. The data showed higher expression levels of FZD7, ß-catenin, c-Myc and cyclinD1, and lower miR-488 expression in mouse endometrial tissues. FZD7 was the target gene of miR-488. Furthermore, elevated miR-488 in isolated mouse endometrial glandular endometrial cells inhibited FZD7, the translocation of ß-catenin to nucleus, the activation of Wnt pathway, and the cell proliferation, migration and invasion. Collectively, these findings indicated that up-regulated miR-488 may reduce the proliferation, migration and invasion of endometrial glandular epithelial cells through inhibiting the activation of Wnt pathway by down-regulating FZD7.
Asunto(s)
Endometriosis/genética , Endometrio/metabolismo , Receptores Frizzled/genética , MicroARNs/genética , Animales , Movimiento Celular/genética , Proliferación Celular/genética , Modelos Animales de Enfermedad , Endometriosis/patología , Endometrio/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Vía de Señalización Wnt/genéticaRESUMEN
Urothelial bladder carcinoma is the ninth most common cancer in the world, with an estimated 150,000 deaths per year. Two comprehensive analysis based on The Cancer Genome Atlas urothelial bladder carcinoma reported that chromatin modifier gene mutations were common in bladder cancer. We aimed to find how the mutations and transcriptional profiles of the genes involving in chromatin modification affected the prognosis of patients. The data were retrieved from the Genomic Data Commons data portal and the gene list in pathway Chromatin Modifying Enzymes were obtained from Reactome. The expression levels and mutational profiles of the genes involving in the chromatin were utilized altogether to construct a fusion patient similarity network by similarity network fusion. The genes that were differentially expressed in one clustered group or two were identified. Fifty chromatin-regulating genes had nonsilent mutations in at least 10 patients. KMT2D, KDM6A, CREBBP, ARID1A, and ARID2 had enriched inactivating mutations. Among 399 cases where both the single-nucleotide polymorphism information and the messenger RNA expression profiles were available, 326, 23, and 50 patients were clustered into Groups 1, 2, and 3, respectively. The survival analysis suggested that the patients in these three groups had a different prognosis. Thity-one genes were identified as differentially expressed in any group. The Gene Ontology term enrichment showed that the differentially expressed genes were enriched in the immune response especially in the complement activation. Altogether, chromatin-regulatory genes were key in bladder cancer and can serve, with the differentially expressed genes, as potential therapeutic targets.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/genética , Ensamble y Desensamble de Cromatina/genética , Mutación , Neoplasias de la Vejiga Urinaria/genética , Adolescente , Adulto , Carcinoma/mortalidad , Carcinoma/patología , Bases de Datos Genéticas , Femenino , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Pronóstico , Factores de Riesgo , Transcriptoma , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Urotelio/patología , Adulto JovenRESUMEN
OBJECTIVE: To explore the image quality (IQ) and diagnostic value of 70 kVp turbo high-pitch coronary CT angiography (THP-CCTA) using automated tube voltage selection (ATVS) and 30 mL of low-concentration contrast agent. METHODS: Patients who underwent 70 kVp THP-CCTA using ATVS with 30 mL of contrast agent (group A) were prospectively enrolled, and those who underwent conventional CCTA (100/120 kVp, prospective sequential mode with 65-75 mL of contrast agent) (group B) were retrospectively selected for study. IQ was assessed subjectively on a 5-point scale, and diagnostic value was assessed based on invasive coronary angiography as the gold standard. Heart rate (HR), HR fluctuation (HRF), body mass index (BMI), effective radiation dose (ED), and iodine uptake (IU) were recorded. RESULTS: A total of 796 patients (398/398 in groups A/B) were included. Between-group differences in age, gender, BMI, HR, HRF, and IQ values were not significant. The ED/IU values were 0.3 ± 0.1 mSv/9.0 ± 0.0 g and 5.8 ± 1.8 mSv/22.9 ± 1.0 g in groups A and B, respectively (p < 0.01). The sensitivity, specificity, positive and negative predictive values, and accuracy of THP-CCTA for the diagnosis of ≥ 50% stenosis were 94.8%, 97.5%, 92.0%, 98.4%, and 96.9% respectively. The mean HR and coronary calcium score were independent predictors of diagnostic image quality, and the best cutoff values were 71.5 bpm and 444.1 respectively. CONCLUSION: This third-generation dual-source CT imaging modality, a 70-kVp THP-CCTA system using ATVS with 30 mL of low-concentration contrast agent, produces high-quality images with high diagnostic accuracy for significant stenosis, with ultra low ED and IU. This technique was most promising in individuals with an HR < 71.5 bpm and coronary calcium score < 444.1. KEY POINTS: ⢠Turbo high-pitch CCTA using 70 kVp via automated tube voltage selection and 30 mL of low-concentration contrast agent is feasible. ⢠This protocol provides high diagnostic accuracy for significant coronary stenosis and reduces radiation doses and iodine uptake significantly. ⢠This protocol was most promising in individuals with an HR < 71.5 bpm and coronary calcium score < 444.1.
Asunto(s)
Angiografía por Tomografía Computarizada/métodos , Medios de Contraste/farmacología , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Prostate cancer is one of the most frequent malignancies affecting men. Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer. LncRNA LOXL1-AS1 participates in the pathogenesis of the exfoliation syndrome. However, the role of LOXL1-AS1 in cancer remains largely unknown. Here, we found that LOXL1-AS1 down-regulation inhibited prostate cancer cell proliferation and cell cycle progression. RNA sequencing analysis revealed that it regulates the expression of cell cycle-related genes. LOXL1-AS1 is predominantly distributed in the cytoplasm, where it interacts with miR-541-3p. In addition, miR-541-3p targets the cell cycle regulator CCND1 in prostate cancer cells. LOXL1-AS1 down-regulation inhibits the expression of CCND1 and cell cycle progression, whereas these effects are abolished upon miR-541-3p suppression. In summary, our study revealed that LOXL1-AS1 regulates prostate cancer cell proliferation and cell cycle progression through miR-541-3p and CCND1. Modulation of their levels may be used to treat prostate cancer.
Asunto(s)
Ciclina D1/genética , MicroARNs/metabolismo , Neoplasias de la Próstata/genética , ARN Largo no Codificante/fisiología , Regiones no Traducidas 3' , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Ciclina D1/metabolismo , Humanos , Masculino , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , ARN Largo no Codificante/metabolismoRESUMEN
Cardiomyocyte apoptosis correlates with the pathogenesis of heart disease. Long noncoding RNA (LncRNA) emerges as a class of noncoding RNAs that regulate gene expression and participate in various cellular processes. However, the role of lncRNAs in cardiomyocyte apoptosis remains to be elucidated. In our study, we found that lncRNA FTX is significantly down-regulated upon ischemia/reperfusion injury and hydrogen peroxide treatment. Enhanced expression of FTX inhibits cardiomyocyte apoptosis induced by hydrogen peroxide. miR-29b-1-5p was found to interact with FTX and regulate the expression of Bcl2l2. Inhibition of miR-29b-1-5p attenuated cardiomyocyte apoptosis upon hydrogen peroxide treatment. We then found that FTX functions as endogenous sponge for miR-29b-1-5p and regulates the activity of miR-29b-1-5p. The results demonstrate that FTX regulates cardiomyocyte apoptosis through modulating the expression of Bcl2l2 which is mediated by miR-29b-1-5p. Our findings reveal a novel regulatory model which is composed of FTX, miR-29b-1-5p and Bcl2l2. Manipulating of their levels may become a new approach to tackling cardiomyocyte apoptosis related heart diseases.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Apoptosis/genética , Apoptosis/fisiología , MicroARNs/genética , Miocitos Cardíacos/fisiología , ARN Largo no Codificante/genética , Animales , Células Cultivadas , Regulación de la Expresión Génica/genética , Masculino , Ratones , Miocitos Cardíacos/citologíaRESUMEN
BACKGROUND: The balance between T helper 17 (Th17) and regulatory T cells (Treg) is a new paradigm in asthma pathogenesis, but no therapeutic targets could modulate the Th17/Treg balance specifically for asthma. Since previous studies have shown the programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis in this disease, we hypothesized that the PD-1/PD-L1 pathway might be involved in the regulation of Treg/Th17 imbalance in asthmatic children. METHODS: The percentage of Treg and Th17 cells and the expression of PD-1 and PD-L1 were detected by flow cytometry in children with asthma and healthy controls. CD4+ T cells were stimulated with Th17 and Treg differentiating factors, and treated with anti-PD-1. Then cells were harvested and measured for Th17 and Treg percentages and Foxp3 and RORγt levels using RT-PCR. RESULTS: We observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 in the two subsets also changed in the mild persistent and moderate to severe persistent groups compared with healthy controls. In vitro, administration of anti-PD-1 could decrease Th17 percentages and RORγt mRNA, and increase Treg percentages and Foxp3 mRNA in CD4+ T cells of children with asthma in the mild persistent and moderate to persistent groups. Additionally, the role played by anti-PD-1 in regulating Treg/Th17 balance was further confirmed in an asthmatic mouse model. CONCLUSION: Alteration of the PD-1/PD-L1 pathway can modulate Treg/Th17 balance in asthmatic children. Treatment with anti-PD-1 posed protective effects on asthma models, providing a novel theoretical target for asthma.
Asunto(s)
Asma/inmunología , Antígeno B7-H1/fisiología , Receptor de Muerte Celular Programada 1/fisiología , Transducción de Señal/fisiología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Animales , Células Cultivadas , Niño , Preescolar , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Receptor de Muerte Celular Programada 1/antagonistas & inhibidoresRESUMEN
Ahead of Print article withdrawn by publisher.
RESUMEN
BACKGROUND: Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. PATIENTS AND METHODS: A case-control study was conducted to investigate the possible associations of IL-27 gene polymorphisms with susceptibility to cervical cancer and clinical outcome. RESULTS: Our results suggested that the IL-27 2905T/G was significantly associated with a decreased risk of cervical cancer. Further analysis showed IL-27 2905T/G genotypes were associated with advanced tumor stages of cervical cancer patients. More interestingly, the IL-27 2905T/G genotypes were statistically significantly associated with the survival in cervical cancer patients. CONCLUSION: Our results showed that the IL-27 2905T/G genotypes were associated with decreased the susceptibility and development of cervical cancer in Chinese Han population.
Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Interleucinas/genética , Neoplasias del Cuello Uterino/genética , Adulto , Anciano , Alelos , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVES: To assess renal cortical perfusion parameter changes using computed tomography (CT) renal perfusion examination in patients with essential hypertension (EH), especially those with EH-related target organ damage (TOD), and to correlate renal perfusion parameters with clinical and laboratory data. METHODS: Consecutive patients with EH (without exclusion criteria) and healthy controls underwent 128-slice dual-source CT perfusion imaging. Quantitative perfusion analysis of renal cortex parameters [blood flow (BF), blood volume, time to peak, and mean transit time] was performed. RESULTS: Ninety-one participants (60 patients with EH, 31 healthy controls) underwent renal perfusion CT imaging, and 84 participants (92.3%) were eligible for perfusion analysis. The BF values were lower in patients with EH than that in controls. Blood flow was correlated with age (P < 0.01), duration of hypertension (P < 0.01), estimated glomerular filtration rate (eGFR; P < 0.01), pulse pressure (P < 0.05), and body mass index (BMI; P < 0.05). Duration of hypertension, eGFR, and BMI were independently associated with BF. No parameter differed between control subjects and those with EH but not. Blood flow was lower in patients with TOD than in control subjects (P < 0.01), but no other parameter differed. Blood flow was lower (P < 0.01) and mean transit time and time to peak were higher (P < 0.05) in the TOD than that in the non-TOD group. CONCLUSIONS: Essential hypertension, especially EH-related TOD, alters renal cortical perfusion parameters, especially BF. Four-dimensional spiral CT renal perfusion examination showed that duration of hypertension, eGFR, and BMI were independently associated with decreased BF.
Asunto(s)
Tomografía Computarizada Cuatridimensional , Hipertensión/fisiopatología , Corteza Renal/irrigación sanguínea , Corteza Renal/diagnóstico por imagen , Adulto , Factores de Edad , Anciano , Comorbilidad , Medios de Contraste , Diabetes Mellitus/epidemiología , Hipertensión Esencial , Femenino , Humanos , Hipertensión/epidemiología , Yohexol/análogos & derivados , Corteza Renal/fisiopatología , Masculino , Persona de Mediana Edad , Intensificación de Imagen Radiográfica , Adulto JovenRESUMEN
Wilms' tumor 1 (Wt1) is a tumor suppressor gene encoding â¼24 zinc finger transcription factors. In the mammalian testis, Wt1 is expressed mostly by Sertoli cells (SCs) involved in testis development, spermatogenesis, and adult Leydig cell (ALC) steroidogenesis. Global knockout (KO) of Wt1 is lethal in mice due to defects in embryogenesis. Herein, we showed that Wt1 is involved in regulating fetal Leydig cell (FLC) degeneration and ALC differentiation during testicular development. Using Wt1(-/flox);Amh-Cre mice that specifically deleted Wt1 in the SC vs. age-matched wild-type (WT) controls, FLC-like-clusters were found in Wt1-deficient testes that remained mitotically active from postnatal day 1 (P1) to P56, and no ALC was detected at these ages. Leydig cells in mutant adult testes displayed morphological features of FLC. Also, FLC-like cells in adult mutant testes had reduced expression in ALC-associated genes Ptgds, Sult1e1, Vcam1, Hsd11b1, Hsd3b6, and Hsd17b3 but high expression of FLC-associated genes Thbs2 and Hsd3b1. Whereas serum LH and testosterone level in mutant mice were not different from controls, intratesticular testosterone level was significantly reduced. Deletion of Wt1 gene also perturbed the expression of steroidogenic enzymes Star, P450c17, Hsd3b6, Hsd3b1, Hsd17b1, and Hsd17b3. FLCs in adult mutant testes failed to convert androstenedione to testosterone due to a lack of Hsd17b3, and this defect was rescued by coculturing with fetal SCs. In summary, FLC-like cells in mutant testes are putative FLCs that remain mitotically active in adult mice, illustrating that Wt1 dictates the fate of FLC and ALC during postnatal testis development.
Asunto(s)
Diferenciación Celular/genética , Células Intersticiales del Testículo/fisiología , Testículo/embriología , Testículo/crecimiento & desarrollo , Proteínas WT1/fisiología , Animales , Embrión de Mamíferos , Feto/embriología , Feto/fisiología , Regulación del Desarrollo de la Expresión Génica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Células de Sertoli/fisiología , Testículo/citologíaRESUMEN
Spermatogenesis is a complex process involving the regulation of multiple cell types. As the only somatic cell type in the seminiferous tubules, Sertoli cells are essential for spermatogenesis throughout the spermatogenic cycle. The Wilms tumor gene, Wt1, is specifically expressed in the Sertoli cells of the mouse testes. In this study, we demonstrated that Wt1 is required for germ cell differentiation in the developing mouse testes. At 10 days post partum, Wt1-deficient testes exhibited clear meiotic arrest and undifferentiated spermatogonia accumulation in the seminiferous tubules. In addition, the expression of claudin11, a marker and indispensable component of Sertoli cell integrity, was impaired in Wt1(-/flox); Cre-ER(TM) testes. This observation was confirmed in in vitro testis cultures. However, the basal membrane of the seminiferous tubules in Wt1-deficient testes was not affected. Based on these findings, we propose that Sertoli cells' status is affected in Wt1-deficient mice, resulting in spermatogenesis failure.
Asunto(s)
Meiosis/fisiología , Células de Sertoli/metabolismo , Espermatogénesis/fisiología , Espermatogonias/metabolismo , Proteínas WT1/metabolismo , Animales , Claudinas/genética , Claudinas/metabolismo , Masculino , Ratones , Ratones Noqueados , Proteínas WT1/genéticaRESUMEN
Genetic polymorphisms in the Fas/Fas ligand (FasL) gene were proposed to be associated with susceptibility to cervical cancer, but previous studies reported controversial findings. We performed a meta-analysis to assess the associations between Fas/FasL polymorphisms and susceptibility to cervical cancer. We carried out a literature search in PubMed and Embase databases for studies on the associations between Fas/FasL polymorphisms and susceptibility to cervical cancer. The associations were assessed by odds ratio (OR) together with its 95% confidence intervals (CIs). Eleven individual studies with a total of 6,919 subjects were finally included into the meta-analysis. Overall, there was no association between Fas 1377G > A polymorphism and susceptibility to cervical cancer (A vs. G: OR = 0.99, 95% CI 0.88-1.12, P = 0.91; AA vs. GG: OR = 1.00, 95% CI 0.76-1.32, P = 0.99; AA/GA vs. GG: OR = 0.95, 95% CI 0.81-1.12, P = 0.54; AA vs. GG/GA: OR = 1.11, 95% CI 0.85-1.43, P = 0.45). In addition, there was also no association between FasL 844 T > C polymorphism and susceptibility to cervical cancer (C vs. T: OR = 1.12, 95% CI 0.91-1.36, P = 0.28; CC vs. TT: OR = 1.17, 95% CI 0.90-1.51, P = 0.24; CC/TC vs. TT: OR = 1.13, 95% CI 0.92-1.39, P = 0.24; CC vs. TT/TC: OR = 1.11, 95% CI 0.83-1.50, P = 0.47). In subgroup analysis by ethnicity, there were also no associations between Fas/FasL polymorphisms and susceptibility to cervical cancer in Asians and Africans. In conclusion, Fas 1377G > A polymorphism and FasL 844 T > C polymorphism are both not associated with susceptibility to cervical cancer.
Asunto(s)
Proteína Ligando Fas/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Neoplasias del Cuello Uterino/genética , Receptor fas/genética , Femenino , Humanos , Riesgo , Neoplasias del Cuello Uterino/etiologíaRESUMEN
Selective glucocorticoid receptor agonists (SEGRAs) are a new class of compounds under clinical evaluation for treatment of ocular inflammation. Widely prescribed therapeutics, such as glucocorticoids, are effective at reducing ocular inflammation, but their long term use predisposes to undesirable side effects. The purpose of this study was to investigate a novel SEGRA, mapracorat (BOL-303242-X), and the differences in mapracorat's mechanism of action compared with traditional steroids (i.e. dexamethasone). Keratocytes from three different humans were cultured and treated with mapracorat or dexamethasone, with and without a strong provoking agent, interleukin (IL)-1ß. The effects of mapracorat compared to dexamethasone were determined by measuring protein levels (Western blotting) and DNA binding (ELISA) for two nuclear factor-kappaB (NF-κB) family members, RelA and RelB. Cytokine production (i.e. IL-6, IL-8, prostaglandin E2 (PGE2)) was characterized by immunoassay. Our findings reveal mechanistic differences between mapracorat and traditional steroid therapies. Mapracorat showed partial attenuation of the classical NF-κB pathway, consistent with traditional steroids. However, mapracorat uniquely potentiated a novel anti-inflammatory mechanism through rapid upregulation of RelB, an anti-inflammatory member of the NF-κB alternative pathway. Mapracorat potently inhibits ocular inflammation in vitro and is a promising new treatment for ocular inflammatory disease. Mapracorat acts, in part, by a novel mechanism via upregulation of RelB in the NF-κB alternative pathway.
Asunto(s)
Antiinflamatorios/farmacología , Benzofuranos/farmacología , Queratocitos de la Córnea/efectos de los fármacos , FN-kappa B/metabolismo , Pentanoles/farmacología , Quinolinas/farmacología , Receptores de Glucocorticoides/agonistas , Factor de Transcripción ReIB/metabolismo , Western Blotting , Células Cultivadas , Queratocitos de la Córnea/metabolismo , Citocinas/metabolismo , Dexametasona/farmacología , Ensayo de Inmunoadsorción Enzimática , Glucocorticoides/farmacología , Humanos , Factor de Transcripción ReIA/metabolismo , Regulación hacia ArribaRESUMEN
A benzoylthiourea-pyrrolidine catalyst was developed for the asymmetric Michael addition of ketones to chalcones. The corresponding products were obtained in high yields with high level of diastereoselectivities (up to 99:1 dr) and high level of enantioselectivities (up to 94% ee) under mild conditions.