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Hollow structures are essential for development and physiological activity. The construction and maintenance of hollow structures never cease throughout the lives of multicellular animals. Epithelial tissue closure is the main strategy used by living organisms to build hollow structures. The high diversity of hollow structures and the simplicity of their development in Drosophila make it an excellent model for the study of hollow structure morphogenesis. In this review, we summarize the tissue closure processes in Drosophila that give rise to or maintain hollow structures and highlight the molecular mechanisms and distinct cell biology involved in these processes.
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OBJECTIVE: This case series study investigated the outcomes of an innovative approach, ansa cervicalis nerve (ACN)-to-recurrent laryngeal nerve (RLN) low-tension anastomosis. METHODS: Patients who received laryngeal nerve anastomosis between May 2015 and September 2021 at the facility were enrolled. The inclusion criteria were patients with RLN dissection and anastomosis immediately during thyroid surgery. Exclusion criteria were cases with anastomosis other than cervical loop-RLN anastomosis or pronunciation recovery time > 6 months. Patients admitted before January 2020 were assigned to group A which underwent the conventional tension-free anastomosis, and patients admitted after January 2020 were group B and underwent the innovative low-tension anastomosis (Dong's method). RESULTS: A total of 13 patients were included, 11 patients received unilateral surgery, and 2 underwent bilateral surgery. For patients who underwent unilateral anastomosis, group B had a significantly higher percentage of normal pronunciation via GRBAS scale (83.3 % vs. 0 %, p = 0.015) and voice handicap index (66.7 % vs. 0 %, p = 0.002), and shorter recovery time in pronunciation (median: 1-day vs. 4 months, p = 0.001) than those in group A after surgery. CONCLUSIONS: ACNs-to-RLN low-tension anastomosis with a laryngeal segment ≤1 cm (Dong's method) significantly improves postoperative pronunciation and recovery time. The results provide clinicians with a new strategy for ACN -to-RLN anastomosis during thyroid surgery.
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Anastomosis Quirúrgica , Fonación , Nervio Laríngeo Recurrente , Tiroidectomía , Humanos , Anastomosis Quirúrgica/métodos , Femenino , Masculino , Persona de Mediana Edad , Nervio Laríngeo Recurrente/cirugía , Tiroidectomía/métodos , Fonación/fisiología , Adulto , Recuperación de la Función , Traqueotomía/métodos , Resultado del Tratamiento , Anciano , Plexo Cervical/cirugía , Traumatismos del Nervio Laríngeo Recurrente/prevención & control , Traumatismos del Nervio Laríngeo Recurrente/etiologíaRESUMEN
Deregulated Wnt signaling and altered lipid metabolism have been linked to obesity, diabetes, and various cancers, highlighting the importance of identifying inhibitors that can modulate Wnt signaling and aberrant lipid metabolism. We have established a Drosophila model with hyperactivated Wnt signaling caused by partial loss of axin, a key component of the Wnt cascade. The Axin mutant larvae are transparent and have severe adipocyte defects caused by up-regulation of ß-catenin transcriptional activities. We demonstrate pharmacologic mitigation of these phenotypes in Axin mutants by identifying bortezomib and additional peptide boronic acids. We show that the suppressive effect of peptide boronic acids on hyperactive Wnt signaling is dependent on α-catenin; the rescue effect is completely abolished with the depletion of α-catenin in adipocytes. These results indicate that rather than targeting the canonical Wnt signaling pathway directly, pharmacologic modulation of ß-catenin activity through α-catenin is a potentially attractive approach to attenuating Wnt signaling in vivo.
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Adipocitos/efectos de los fármacos , Ácidos Borónicos/farmacología , Péptidos/farmacología , Proteínas Wnt/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Animales , Proteína Axina/metabolismo , Drosophila/efectos de los fármacos , Drosophila/metabolismo , Transcripción Genética/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , beta Catenina/metabolismoRESUMEN
Cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC) play conserved roles in modulating RNA polymerase II (Pol II)-dependent gene expression. To understand the structure and function relations of CDK8, we analyzed the structures of human and Drosophila CDK8 proteins using molecular dynamics simulations, combined with functional analyses in Drosophila. Specifically, we evaluated the structural differences between hCDK8 and dCDK8 to predict the effects of the LXXLL motif mutation (AQKAA), the P154L mutations, and drug binding on local structures of the CDK8 proteins. First, we have observed that both the LXXLL motif and the kinase activity of CDK8 are required for the normal larval-to-pupal transition in Drosophila. Second, our molecular dynamic analyses have revealed that hCDK8 has higher hydrogen bond occupation of His149-Asp151 and Asp151-Asn156 than dCDK8. Third, the substructure of Asp282, Phe283, Arg285, Thr287 and Cys291 can distinguish human and Drosophila CDK8 structures. In addition, there are two hydrogen bonds in the LXXLL motif: a lower occupation between L312 and L315, and a relatively higher occupation between L312 and L316. Human CDK8 has higher hydrogen bond occupation between L312 and L316 than dCDK8. Moreover, L312, L315 and L316 in the LXXLL motif of CDK8 have the specific pattern of hydrogen bonds and geometries, which could be crucial for the binding to nuclear receptors. Furthermore, the P154L mutation dramatically decreases the hydrogen bond between L312 and L315 in hCDK8, but not in dCDK8. The mutations of P154L and AQKAA modestly alter the local structures around residues 154. Finally, we identified the inhibitor-induced conformational changes of hCDK8, and our results suggest a structural difference in the drug-binding site between hCDK8 and dCDK8. Taken together, these results provide the structural insights into the roles of the LXXLL motif and the kinase activity of CDK8 in vivo.
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Secuencias de Aminoácidos , Sitios de Unión , Quinasa 8 Dependiente de Ciclina/química , Proteínas de Drosophila/química , Modelos Moleculares , Dominios y Motivos de Interacción de Proteínas , Inhibidores de Proteínas Quinasas/química , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Quinasa 8 Dependiente de Ciclina/antagonistas & inhibidores , Proteínas de Drosophila/antagonistas & inhibidores , Humanos , Enlace de Hidrógeno , Ligandos , Conformación Molecular , Mutación , Unión Proteica , Inhibidores de Proteínas Quinasas/farmacología , Especificidad de la Especie , Relación Estructura-ActividadRESUMEN
The complex interplay between genetic and environmental factors, such as diet and lifestyle, defines the initiation and progression of multifactorial diseases, including cancer, cardiovascular and metabolic diseases, and neurological disorders. Given that most of the studies have been performed in controlled experimental settings to ensure the consistency and reproducibility, the impacts of environmental factors, such as dietary perturbation, on the development of animals with different genotypes and the pathogenesis of these diseases remain poorly understood. By analyzing the cdk8 and cyclin C (cycC) mutant larvae in Drosophila, we have previously reported that the CDK8-CycC complex coordinately regulates lipogenesis by repressing dSREBP (sterol regulatory element-binding protein)-activated transcription and developmental timing by activating EcR (ecdysone receptor)-dependent gene expression. Here we report that dietary nutrients, particularly proteins and carbohydrates, modulate the developmental timing through the CDK8/CycC/EcR pathway. We observed that cdk8 and cycC mutants are sensitive to the levels of dietary proteins and seven amino acids (arginine, glutamine, isoleucine, leucine, methionine, threonine, and valine). Those mutants are also sensitive to dietary carbohydrates, and they are more sensitive to monosaccharides than disaccharides. These results suggest that CDK8-CycC mediates the dietary effects on lipid metabolism and developmental timing in Drosophila larvae.
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Quinasa 8 Dependiente de Ciclina/fisiología , Proteínas de Drosophila/fisiología , Larva/metabolismo , Necesidades Nutricionales/fisiología , Animales , Ciclina C/metabolismo , Ciclina C/fisiología , Quinasa 8 Dependiente de Ciclina/metabolismo , Dieta , Proteínas en la Dieta/metabolismo , Drosophila/embriología , Drosophila/genética , Proteínas de Drosophila/metabolismo , Expresión Génica , Reproducibilidad de los ResultadosRESUMEN
The steroid hormone ecdysone and its receptor (EcR) play critical roles in orchestrating developmental transitions in arthropods. However, the mechanism by which EcR integrates nutritional and developmental cues to correctly activate transcription remains poorly understood. Here, we show that EcR-dependent transcription, and thus, developmental timing in Drosophila, is regulated by CDK8 and its regulatory partner Cyclin C (CycC), and the level of CDK8 is affected by nutrient availability. We observed that cdk8 and cycC mutants resemble EcR mutants and EcR-target genes are systematically down-regulated in both mutants. Indeed, the ability of the EcR-Ultraspiracle (USP) heterodimer to bind to polytene chromosomes and the promoters of EcR target genes is also diminished. Mass spectrometry analysis of proteins that co-immunoprecipitate with EcR and USP identified multiple Mediator subunits, including CDK8 and CycC. Consistently, CDK8-CycC interacts with EcR-USP in vivo; in particular, CDK8 and Med14 can directly interact with the AF1 domain of EcR. These results suggest that CDK8-CycC may serve as transcriptional cofactors for EcR-dependent transcription. During the larval-pupal transition, the levels of CDK8 protein positively correlate with EcR and USP levels, but inversely correlate with the activity of sterol regulatory element binding protein (SREBP), the master regulator of intracellular lipid homeostasis. Likewise, starvation of early third instar larvae precociously increases the levels of CDK8, EcR and USP, yet down-regulates SREBP activity. Conversely, refeeding the starved larvae strongly reduces CDK8 levels but increases SREBP activity. Importantly, these changes correlate with the timing for the larval-pupal transition. Taken together, these results suggest that CDK8-CycC links nutrient intake to developmental transitions (EcR activity) and fat metabolism (SREBP activity) during the larval-pupal transition.
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Ciclina C/metabolismo , Quinasa 8 Dependiente de Ciclina/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/crecimiento & desarrollo , Drosophila/metabolismo , Receptores de Esteroides/metabolismo , Animales , Animales Modificados Genéticamente , Ciclina C/genética , Quinasa 8 Dependiente de Ciclina/genética , Proteínas de Unión al ADN/metabolismo , Drosophila/genética , Proteínas de Drosophila/genética , Ecdisteroides/biosíntesis , Femenino , Privación de Alimentos , Regulación de la Expresión Génica , Larva/crecimiento & desarrollo , Larva/metabolismo , Mutación , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Colorectal cancer is a common malignant tumor with high incidence affecting the digestive system. This study aimed to identify the key genes relating to prognosis of colorectal cancer and to construct a prognostic model for its risk evaluation. Gene expression profiling of colorectal cancer patients, GSE17537, was downloaded from Gene Expression Omnibus database (GEO). A total of 55 samples from patients ranging from stages 1 to 4 were available. Differentially expressed genes were screened, with which single factor survival analysis was performed to identify the response genes. Interacting network and KEGG enrichment analysis of responsive genes were performed to identify key genes. In return, Fisher enrichment analysis, literature mining, and Kaplan-Meier analysis were used to verify the effectiveness of the prognostic model. The 20-gene model generated in this study posed significant influences on the prognoses (P = 9.691065e-09). Significance was verified via independent dataset GSE38832 (P = 9.86581e-07) and GSE17536 (P = 2.741e-08). The verified effective 20-gene model could be utilized to predict prognosis of patients with colorectal cancer and would contribute to post-operational treatment and follow-up strategies. J. Cell. Biochem. 118: 3675-3685, 2017. © 2017 Wiley Periodicals, Inc.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Bases de Datos Genéticas , Regulación Neoplásica de la Expresión Génica , Modelos Genéticos , Neoplasias Colorrectales/metabolismo , HumanosRESUMEN
BACKGROUND: Feminization of animals derived from areas polluted by endocrine disrupting chemicals (EDCs) has been observed in all classes of vertebrates. However, feminization of artificially reared offspring by feeding of specific living organisms has never been reported. METHODS: Different food (including Limnodilus spp collected from the wild) and time treatment were applied to southern catfish. In addition, EDCs in Limnodilus spp., an annelid worm collected from wild contaminated small streams, was detected by LC-MS (Liquid chromatography-mass spectrometry). Serum estradiol-17ß and vitellogenin (VTG) levels and gonadal Sf1, Dmrt1, Foxl2, Cyp19a1a expression levels in the catfish were measured through Estradiol/VTG EIA Kit and real-time PCR. RESULTS: Here we report that feeding of Limnodilus spp. resulted in complete feminization of southern catfish, which has a 1:1 sex ratio in wild conditions. Furthermore, HPLC analysis showed that the extraction of Limnodilus spp. contained EDCs, including bisphenol A (BPA), diethylstilbestrol (DES), 4-tert-octylphenol (4-t-OP) and 4-nonylphenol (4-NP), which were further confirmed by LC-MS. Feeding southern catfish using commercial diets sprayed with EDCs cocktail also resulted in 100% female, whereas the control fish displayed approximate 1:1 sex ratio. Limnodilus spp. fed fish displayed similar serum estradiol-17ß and VTG levels and gonadal Sf1, Dmrt1, Foxl2, Cyp19a1a expression levels to those of female control. CONCLUSION: These results demonstrated that EDCs in Limnodilus spp. cause southern catfish feminization by affecting aromatase expression and endogenous estrogen level. This is the first report showing that feeding of any living organism resulted in complete feminization of a vertebrate.
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Anélidos/química , Bagres , Disruptores Endocrinos/análisis , Feminización/inducido químicamente , Contaminación Química del Agua/efectos adversos , Animales , Cromatografía Liquida , Disruptores Endocrinos/efectos adversos , Femenino , Gónadas/metabolismo , Gónadas/patología , Masculino , Espectrometría de Masas , Diferenciación Sexual , Vitelogeninas/sangreRESUMEN
PURPOSE: This study aimed to evaluate the factors associated with bilateral papillary thyroid carcinoma (PTC) and lateral cervical lymph node metastasis (LLNM) in patients with suspicious unilateral PTC. METHODS: This study analyzed patients with suspicious unilateral PTC who were enrolled in a university hospital between 2016 and 2019 in Zhejiang, China. Using logistic regression, the study examined the factors associated with bilateral PTC and LLNM in demographic data, anthropometric measurements, lifestyle factors, medical history, preoperative diagnostic tests, and histopathological factors. RESULTS: A total of 256 patients, with a mean age of 49 years, were enrolled. Bilateral PTC was associated with multifocality (aOR: 5.069, 95% CI: 2.440-10.529, P < 0.001), and contralateral nodule in the upper (aOR: 9.073, 95% CI: 2.111-38.985, P = 0.003) and middle (aOR: 9.926, 95% CI: 2.683-36.717, P < 0.001). LLNM was positively associated with bilateral PTC (aOR, 4.283, 95% CI: 1.378-13.308, p = 0.012), male (aOR, 3.377, 95% CI: 1.205-9.461, P = 0.021), upper location of carcinoma (aOR, 3.311, 95% CI: 1.091-10.053, p = 0.035), and punctate echogenic foci (aOR, 3.309, 95% CI: 1.165-9.394, P = 0.025). Contralateral maximal nodule in the upper (aOR: 0.098, 95% CI: 0.015-0.628, p = 0.014), middle (aOR: 0.114, 95% CI: 0.033-0.522, p < 0.001), and lower (aOR, 0.028, 95% CI: 0.003-0.276, P = 0.002) location were inversely associated with LLNM. CONCLUSION: Upper and middle location of contralateral nodule and tumor multifocality predicted the risk bilateral PTC. Bilateral PTC, male, upper tumor location, punctate echogenic foci and contralateral nodule location in the entire lobes were independent predictors for LLNM.
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Metástasis Linfática , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Masculino , Persona de Mediana Edad , Femenino , Nódulo Tiroideo/patología , Nódulo Tiroideo/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/diagnóstico por imagen , Metástasis Linfática/patología , Cáncer Papilar Tiroideo/patología , Adulto , Cuello/patología , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Anciano , China/epidemiología , Factores de RiesgoRESUMEN
Aim: This study aimed to identify molecular markers associated with papillary thyroid cancer (PTC) and investigate the therapeutic potential of targeted nanoscale drugs. Materials & methods: We analyzed the effects of circICA1 and miR-486-3p on B-CPAP cells' proliferation, apoptosis, migration and invasion. The regulation of the miR-486-3p/SERPINA1 axis was explored using quantitative real-time reverse transcription PCR and western blot analyses for metastasis. In vivo, we evaluated the effects of hyperbranched polyamidoamine-RGD peptide/si-circICA1 on PTC growth and metastasis. Results: Enhanced miR-486-3p expression inhibits B-CPAP cells' proliferation and invasion. si-circICA1 delivered via hyperbranched polyamidoamine-RGD peptide nanoparticles shows potential for treating metastasis in PTC. Conclusion: This study identifies key molecular mechanisms underlying PTC invasiveness and suggests a promising therapeutic strategy for PTC using targeted nanoscale drugs.
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MicroARNs , Oligopéptidos , Poliaminas , Neoplasias de la Tiroides , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Invasividad Neoplásica/genética , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Cáncer Papilar Tiroideo/tratamiento farmacológico , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Proliferación Celular , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , alfa 1-Antitripsina/metabolismoRESUMEN
Instead of employing telomerases to safeguard chromosome ends, dipteran species maintain their telomeres by transposition of telomeric-specific retrotransposons (TRs): in Drosophila , these are HeT-A , TART , and TAHRE . Previous studies have shown how these TRs create tandem repeats at chromosome ends, but the exact mechanism controlling TR transcription has remained unclear. Here we report the identification of multiple subunits of the transcription cofactor Mediator complex and transcriptional factors Scalloped (Sd, the TEAD homolog in flies) and E2F1-Dp as novel regulators of TR transcription and telomere length in Drosophila . Depletion of multiple Mediator subunits, Dp, or Sd increased TR expression and telomere length, while over-expressing E2F1-Dp or knocking down the E2F1 regulator Rbf1 (Retinoblastoma-family protein 1) stimulated TR transcription, with Mediator and Sd affecting TR expression through E2F1-Dp. The CUT&RUN analysis revealed direct binding of CDK8, Dp, and Sd to telomeric repeats. These findings highlight the essential role of the Mediator complex in maintaining telomere homeostasis by regulating TR transcription through E2F1-Dp and Sd, revealing the intricate coupling of TR transcription with the host cell-cycle machinery, thereby ensuring chromosome end protection and genomic stability during cell division.
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Increasing concerns about hair loss affect people's quality of life. Recent studies have found that sympathetic nerves play a positive role in regulating hair follicle stem cell activity to promote hair growth. However, no study has investigated sympathetic innervation of transplanted follicles. Rat vibrissa follicles were extracted and implanted under the dorsal skin of BALB/c-nu/nu mice using one of two types of follicles: (1) intact follicles, where transplants included bulbs, and (2) upper follicles, where transplants excluded bulbs. Follicular samples were collected for hematoxylin and eosin staining, immunofluorescence staining for tyrosine hydroxylase (TH, a sympathetic marker) and enzyme-linked immunosorbent assays. At 37 days after implantation in both groups, follicles had entered anagen, with the growth of long hair shafts; tyrosine-hydroxylase-positive nerves were innervating follicles (1.45-fold); and norepinephrine concentrations (2.03-fold) were significantly increased compared to 5 days, but did not return to normal. We demonstrate the survival of intact and upper follicle xenografts and the partial restoration of sympathetic reinnervations of both transplanted follicles.
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Fibroma/cirugía , Neoplasias Cardíacas/cirugía , Válvula Tricúspide/cirugía , Disnea/etiología , Ecocardiografía , Fibroma/complicaciones , Fibroma/diagnóstico por imagen , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/diagnóstico por imagen , Humanos , Hallazgos Incidentales , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/patología , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/etiologíaRESUMEN
OBJECTIVE: To establish an extracorporeal circulation (ECC) rat model, and evaluate the inflammatory response and organ injury induced in the model. METHODS: SD rats were anesthetized and cannulated from right common carotid artery to left femoral vein to establish the bypass of extracorporeal circulation. Then the rats were randomly divided into ECC group and sham group. The rats in ECC group were subjected to extracorporeal circulation for 2 hours and then rest for 2 hours, while the rats in sham group were only observed for 4 hours without extracorporeal circulation. After that, blood routine examination, blood gas analysis, the measurement of pro-inflammatory factors in bronchoalveolar lavage fluid and lung tissue were performed to evaluate the lung injury induced by ECC. Circulating endothelial cells were also calculated by flow cytometry to assess the vascular endothelial injury. RESULTS: At 2 hours after ECC, red blood cell counts in both groups kept normal, while leukocyte and neutrophil counts, plasmatic tumor necrosis factor-a level and neutrophil elastase level, circulating endothelial cells in the rats of ECC group were significantly higher than those in sham group. Tumor necrosis factor-alpha in bronchoalveolar lavage fluid and water content in lung of the ECC rats were also significantly higher, while the oxygenation index was significantly lower. Neutrophil infiltration was also observed in lung tissues with increased thickness of alveolar membrane in ECC group. CONCLUSION: The ECC model established from right common carotid artery to left femoral vein in our study can successfully induce systemic inflammatory response, and acute lung injury associated with inflammation.
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Circulación Extracorporea/efectos adversos , Modelos Animales , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Lesión Pulmonar Aguda/etiología , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Thyroid cancer is one of the most common endocrine malignancies. It is necessary to discover more effective molecular targets for the treatment of thyroid cancer. The results of immunohistochemical staining, qPCR and Western blot indicated that the expression of SYT7 in thyroid cancer tissues and cells was higher than that in paracarcinoma tissues and normal thyroid cells. Through cell function testing experiments, it was found that SYT7 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis, while SYT7 overexpression had the opposite effect. Similarly, SYT7 downregulation also suppressed tumor growth in vivo. HMGB3 was confirmed to be the downstream gene of SYT7 by GeneChip and Ingenuity Pathway Analysis. Besides, through UbiBrowser database predictions and Co-IP assays, we found that SYT7 interacted with BRCA1 to inhibit HMGB3 ubiquitination and thus upregulated the protein level of HMGB3. Similar to SYT7, HMGB3 was significantly upregulated in thyroid cancer. HMGB3 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis. Furthermore, HMGB3 knockdown restored the promotion of cell proliferation and migration caused by SYT7 overexpression. SYT7 and HMGB3 were upregulated in thyroid cancer, and SYT7 regulated the expression of HMGB3 through BRCA1-mediated ubiquitination of HMGB3 to promote thyroid cancer progression.
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Proteína HMGB3 , MicroARNs , Neoplasias de la Tiroides , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteína HMGB3/genética , Proteína HMGB3/metabolismo , Humanos , MicroARNs/genética , Sinaptotagminas/genética , Sinaptotagminas/metabolismo , Neoplasias de la Tiroides/genética , UbiquitinaciónRESUMEN
BACKGROUND: Increasing evidence suggests that a close interaction of Kupffer cells with T cells plays a central role in concanavalin A-induced hepatic injury in mice, but the underlying mechanisms remain obscure. The present study aimed to determine the relative roles of Th1 and Th17 type responses in concanavalin A-induced hepatic injury in mice, and to investigate whether or not Kupffer cells contribute to hepatic injury via a Th1 or Th17 type response-dependent pathway. METHODS: Immune-mediated hepatic injury was induced in C57BL/6 mice by intravenous injection of concanavalin A. Kupffer cells were inactivated by pretreatment with gadolinium chloride 24 hours before the concanavalin A injection. The interferon-gamma (IFN-gamma) and interleukin-17 (IL-17) pathways were blocked by specific neutralizing antibodies. Hepatic injury was assessed using serum transferase activity and pathological analysis. Expression of inflammatory cytokines within the liver was detected by real-time polymerase chain reaction and immunohistochemistry. RESULTS: Neutralization of IFN-gamma significantly attenuated concanavalin A-induced hepatic injury. However, neutralization of IL-17 failed to suppress the injury. Inactivation of Kupffer cells by gadolinium chloride pretreatment protected against concanavalin A-induced injury and significantly reduced hepatic cytokine levels including TNF-alpha, IL-6 and IFN-gamma but not IL-17. CONCLUSION: Our findings suggest that Kupffer cells contribute to concanavalin A-induced hepatic injury via a Th1 type response-dependent pathway and production of inflammatory cytokines including TNF-alpha, IL-6 and IFN-gamma.
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Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Concanavalina A/toxicidad , Macrófagos del Hígado/fisiología , Células TH1/inmunología , Células Th17/inmunología , Animales , Femenino , Gadolinio/farmacología , Interferón gamma/biosíntesis , Interleucina-17/biosíntesis , Ratones , Ratones Endogámicos C57BLRESUMEN
Endo-beta-1,4-D-glucanases (EGases) are a widespread and vital group of glycosyl hydrolases that generally break the beta-1,4-glucosyl linkages. Studies of plant EGases have mainly been concentrated on vegetative growth, while little is currently known about their role in reproductive processes. Using the GUS reporter aided analysis of promoter activities, we identified the expression patterns of two putative Arabidopsis EGases genes (At3g43860 and At4g39000) whose promoters conferred specific localization of the GUS activity in reproductive organs. We found that At3g43860, which is similar to KOR in its protein structural organization, is expressed in mature pollen and the pollen tube, implying that it may have a role in pollen and pollen tube growth. At4g39000 was found to be activated in the developing ovules and seeds, especially at the micropylar end of the inner integuments and nucellus in a proximal-distal pattern. Our results suggested that the two EGases play specific roles in Arabidopsis sexual reproduction.
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Proteínas de Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Celulasa/genética , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Arabidopsis/enzimología , Análisis de Secuencia por Matrices de Oligonucleótidos , Polen/enzimología , Polen/genética , Regiones Promotoras Genéticas , Reproducción/genética , Semillas/enzimología , Semillas/genéticaRESUMEN
PURPOSE: The relationship between large thyroid nodules and the risk of malignancy is controversial. This study aimed to examine the relationship between thyroid nodule size and the risk of malignancy of maximal thyroid nodules ≥2 cm and the risk of accompanied by occult thyroid carcinoma. METHODS: This was a retrospective study of patients who underwent near-total or total thyroidectomy for thyroid nodules from January 2016 to January 2019 at the First Affiliated Hospital,Zhejiang University School of Medicine. Clinical, biochemical, and pathological characteristics were examined for association with malignancy using univariable, multivariable, and receiver operating characteristic curve analyses. RESULTS: Finally, 367 patients (277 females (75.5%) and 90 males (24.5%)) with a mean age of 49.0±13.5 years were included. Multivariable logistic regression analysis showed that age (OR=0.959, 95% CI: 0.939-0.979, P<0.001), Hashimoto's thyroiditis (OR=2.437, 95% CI: 1.162-5.112, P=0.018), the diameter of maximal nodule (small) (OR=0.706, 95% CI: 0.541-0.919, P=0.010), and punctate echogenic foci (OR=2.837, 95% CI: 1.598-5.286, P<0.001) were independently associated with malignancy. Of 223 patients who had non-suspicious malignant nodules (TI-RADS <4), 12.7% (n=29) patients showed malignancy at postoperative pathology. Only age was associated with occult PTC in the univariable analyses (OR=0.962, 95% CI: 0.934-0.991, P=0.011). When TPOAb was used as a continuous variable for statistical analysis, it showed a significant difference in the ROC curve, and the results showed TPOAb >31.4 mIU/L was more associated with occult PTC (P=0.006). A predictive model including four independent risk factors of malignancy showed an optimal discriminatory accuracy (area under the curve, AUC) of 0.783 (95% CI=0.732-0.833). CONCLUSION: Relatively young age (<54.5 years), Hashimoto's thyroiditis, the diameter of the maximal nodule, and punctate echogenic foci were independently associated with thyroid malignancy in patients with maximal thyroid nodules ≥2 cm. Young age (<54.5 years) and TPOAb >31.4 mIU/L were associated with occult PTC.