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OBJECTIVES: We conducted the first trial to evaluate the effect that fire-needle acupuncture at Neiyingxiang (ExHN 9) in patients with moderate to severe persistent AR. METHODS: This was a randomized, single-center, sham, and placebo-controlled rial. Patients were kept blinded to their group assignment. All participants were equally assigned to the fire-needle acupuncture (FA) treatment group, sham fire-needle acupuncture (SFA) group, or loratadine group. The trial was designed with an acupuncture intervention once a week for 4 weeks and follow-up 4 weeks. The Total Nasal Symptom Scores (TNSS), Total Non-Nasal Symptom Scores (TNNSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Allergic Rhinitis Control Test (ARCT), and total nasal resistance of 150 Pa were evaluated as outcome measures. RESULTS: A total of 180 participants were enrolled, and 175 participants completed the trials. At 2 and 4 weeks, the TNSS, TNNSS, and RQLQ scores of the FA and loratadine groups were significantly lower than those of the SFA group. At 8 weeks, the scores of loratadine group increased compared with the FA group (Cohen's d >0.80, p < 0.01). The ACRT score of the FA treatment group rose gradually. After treatment, the total nasal resistance of the FA group was significantly decreased and was lower than that of the other two groups (Cohen's d >0.80, p < 0.01). CONCLUSION: Fire-needle acupuncture at Neiyingxiang (ExHN 9) is effective for improving nasal allergy symptoms and quality of life in patients with moderate and severe persistent AR, and the duration of its effects is long. LEVEL OF EVIDENCE: 2 Laryngoscope, 2024.
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The placenta is a crucial determinant of fetal survival, growth, and development. Deficiency in placental development directly causes intrauterine growth retardation (IUGR). IUGR can lead to fetal growth restriction and an increase in the mortality rate. The genetic mechanisms underlying IUGR development, however, remain unclear. In the present study, we integrated whole-genome DNA methylation and transcriptomic analyses to determine distinct gene expression patterns in various placental tissues to identify pivotal genes that are implicated with IUGR development. By performing RNA-sequencing analysis, 1487 differentially expressed genes (DEGs), with 737 upregulated and 750 downregulated genes, were identified in IUGR pigs (H_IUGR) compared with that in normal birth weight pigs (N_IUGR) (p < 0.05); furthermore, 77 miRNAs, 1331 lncRNAs, and 61 circRNAs were differentially expressed. The protein-protein interaction network analysis revealed that among these DEGs, the genes GNGT1, ANXA1, and CDC20 related to cellular developmental processes and blood vessel development were the key genes associated with the development of IUGR. A total of 495,870 differentially methylated regions were identified between the N_IUGR and H_IUGR groups, which included 25,053 differentially methylated genes (DMEs); moreover, the overall methylation level was higher in the H_IUGR group than in the N_IUGR group. Combined analysis showed an inverse correlation between methylation levels and gene expression. A total of 1375 genes involved in developmental processes, tissue development, and immune system regulation exhibited methylation differences in gene expression levels in the promoter regions and gene ontology regions. Five genes, namely, ANXA1, ADM, NRP2, SHH, and SMAD1, with high methylation levels were identified as potential contributors to IUGR development. These findings provide valuable insights that DNA methylation plays a crucial role in the epigenetic regulation of gene expression and mammalian development and that DNA-hypermethylated genes contribute to IUGR development in Rongchang pigs.
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Metilação de DNA , Retardo do Crescimento Fetal , Placenta , Animais , Retardo do Crescimento Fetal/genética , Suínos , Feminino , Gravidez , Placenta/metabolismo , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas/genética , Epigênese Genética , MicroRNAs/genética , Transcriptoma/genética , Redes Reguladoras de GenesRESUMO
RATIONALE: In recent decades, the incidence of perennial allergic rhinitis (PAR) has been increasing annually. However, some patients could not achieve adequate symptomatic relief with routine pharmacological treatment. Consequently, there exists an urgent clinical imperative for the development of safe and efficacious treatments with sustained therapeutic impact to ameliorate the symptomatic burden and enhance the quality of life. PATIENT CONCERNS: The patient was a 35-year-old woman. She had suffered moderate and severe refractory PAR for decades and failed to sustain symptom mitigation from regular treatment. DIAGNOSES: Perennial allergic rhinitis. INTERVENTIONS: The patient underwent a 4-week course of fire needle acupuncture at Neiyingxiang, administered weekly, during which all allopathic medication was discontinued. OUTCOMES: The total nasal symptoms score, total non nasal symptoms score, rhinoconjunctivitis quality of life questionnaire, and the total nasal resistance of the patient were decreased after treatment and achieved symptomatic relief. Follow-up conducted 3 months post-treatment revealed enduring symptom relief, with only sporadic nasal congestion elicited by cold stimulus. LESSONS: This case proves that, fire needle acupuncture at Neiyingxiang may be beneficial in treating moderate and severe refractory PAR patient and have a lasting effect.
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Terapia por Acupuntura , Acupuntura , Rinite Alérgica Perene , Rinite Alérgica , Feminino , Humanos , Adulto , Qualidade de Vida , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/tratamento farmacológico , Resultado do Tratamento , Rinite Alérgica/terapiaRESUMO
Grain weight is an important determinant of grain yield. However, the underlying regulatory mechanisms for grain size remain to be fully elucidated. Here, we identify a rice mutant grain weight 9 (gw9), which exhibits larger and heavier grains due to excessive cell proliferation and expansion in spikelet hull. GW9 encodes a nucleus-localized protein containing both C2H2 zinc finger (C2H2-ZnF) and VRN2-EMF2-FIS2-SUZ12 (VEFS) domains, serving as a negative regulator of grain size and weight. Interestingly, the non-frameshift mutations in C2H2-ZnF domain result in increased plant height and larger grain size, whereas frameshift mutations in both C2H2-ZnF and VEFS domains lead to dwarf and malformed spikelet. These observations indicated the dual functions of GW9 in regulating grain size and floral organ identity through the C2H2-ZnF and VEFS domains, respectively. Further investigation revealed the interaction between GW9 and the E3 ubiquitin ligase protein GW2, with GW9 being the target of ubiquitination by GW2. Genetic analyses suggest that GW9 and GW2 function in a coordinated pathway controlling grain size and weight. Our findings provide a novel insight into the functional role of GW9 in the regulation of grain size and weight, offering potential molecular strategies for improving rice yield.
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Oryza , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Ubiquitinação , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
Grain size is an important determinant of grain yield in rice. Although dozens of grain size genes have been reported, the molecular mechanisms that control grain size remain to be fully clarified. Here, we report the cloning and characterization of GR5 (GRAIN ROUND 5), which is allelic to SMOS1/SHB/RLA1/NGR5 and encodes an AP2 transcription factor. GR5 acts as a transcriptional activator and determines grain size by influencing cell proliferation and expansion. We demonstrated that GR5 physically interacts with five Gγ subunit proteins (RGG1, RGG2, DEP1, GS3, and GGC2) and acts downstream of the G protein complex. Four downstream target genes of GR5 in grain development (DEP2, DEP3, DRW1, and CyCD5;2) were revealed and their core T/CGCAC motif identified by yeast one-hybrid, EMSA, and ChIP-PCR experiments. Our results revealed that GR5 interacts with Gγ subunits and cooperatively determines grain size by regulating the expression of downstream target genes. These findings provide new insight into the genetic regulatory network of the G protein signaling pathway in the control of grain size and provide a potential target for high-yield rice breeding.
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Oryza , Oryza/metabolismo , Redes Reguladoras de Genes , Grão Comestível/genética , Grão Comestível/metabolismo , Transdução de Sinais , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismoRESUMO
This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.
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Genoma , Modelos Genéticos , Suínos/genética , Animais , Fenótipo , Genômica/métodos , Genótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Mitochondrion is the key respiratory organ and participate in multiple anabolism and catabolism pathways in eukaryote. However, the underlying mechanism of how mitochondrial membrane proteins regulate leaf and grain development remains to be further elucidated. RESULTS: Here, a mitochondria-defective mutant narrow leaf and slender grain 1 (nlg1) was identified from an EMS-treated mutant population, which exhibits narrow leaves and slender grains. Moreover, nlg1 also presents abnormal mitochondria structure and was sensitive to the inhibitors of mitochondrial electron transport chain. Map-based cloning and transgenic functional confirmation revealed that NLG1 encodes a mitochondrial import inner membrane translocase containing a subunit Tim21. GUS staining assay and RT-qPCR suggested that NLG1 was mainly expressed in leaves and panicles. The expression level of respiratory function and auxin response related genes were significantly down-regulated in nlg1, which may be responsible for the declination of ATP production and auxin content. CONCLUSIONS: These results suggested that NLG1 plays an important role in the regulation of leaf and grain size development by maintaining mitochondrial homeostasis. Our finding provides a novel insight into the effects of mitochondria development on leaf and grain morphogenesis in rice.
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Oryza , Oryza/genética , Membranas Mitocondriais , Folhas de Planta/genética , Mitocôndrias , Grão Comestível/genética , Ácidos Indolacéticos , Proteínas de Membrana/genéticaRESUMO
This study investigates the distribution, structural properties, and potential impacts of oceanic processes on microplastics (MPs) in the Taiwan Strait (TWS) and surrounding seas. With an average of 174 particles/m3, the MP abundance in surface seawater ranged from 84 to 389 particles/m3. MP abundance ranged from 16 to 382 particles/kg in sediments, with a median of 121 particles/kg. Fragment and fiber were the two most frequently detected shapes. These MPs were found to be composed primarily of carbon and oxygen elements at 70-90% levels using energy-dispersive X-ray spectroscopy. Additionally, several examples had trace levels of metallic components. Black was the color that MPs saw the most often out of all the hues. The two main types of polymers are polyester and rayon, and their production is influenced by home sewage discharge and synthetic fiber production. The main routes of MP transport were land source input, riverine input, and oceanic currents. This study showed that salinity affects the distribution of MPs, with high-salinity seawater serving to saturate their presence. On the other hand, upwelling raises MP concentrations by bringing nutrients from the deep to the surface. Furthermore, it has been discovered that the dilution of the Pearl River plume increases the MP prevalence in the region. The South China Sea Warm Current had the highest lateral MPs transport flux (2.1 × 1014 particles/y), which was followed by the Taiwan Strait Current area (1.0 × 1014 particles/y) and the Guangdong coastal areas (8.6 × 1013 particles/y). In sediments, the MP prevalence was inversely correlated with particle size. Flocculation processes probably made it easier for MPs to travel down the water column and deposit themselves on the aquatic substrate. Although the relationship between MPs, total organic carbon, and total organic nitrogen was not correlated, a favorable trend showed that MPs may discreetly contribute to carbon storage in coastal sediment.
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Microplásticos , Poluentes Químicos da Água , Plásticos , Taiwan , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Oceanos e Mares , CarbonoRESUMO
Leaf and panicle are important nutrient and yield organs in rice, respectively. Although several genes controlling lesion mimic leaf and panicle abortion have been identified, a few studies have reported the involvement of a single gene in the production of both the traits. In this study, we characterized a panicle abortion mutant, lesion mimic leaf and panicle apical abortion (lmpa), which exhibits lesions on the leaf and causes degeneration of apical spikelets. Molecular cloning revealed that LMPA encodes a proton pump ATPase protein that is localized in the plasma membrane and is highly expressed in leaves and panicles. The analysis of promoter activity showed that the insertion of a fragment in the promoter of lmpa caused a decrease in the transcription level. Cellular and histochemistry analysis indicated that the ROS accumulated and cell death occurred in lmpa. Moreover, physiological experiments revealed that lmpa was more sensitive to high temperatures and salt stress conditions. These results provide a better understanding of the role of LMPA in panicle development and lesion mimic formation by regulating ROS homeostasis.
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BACKGROUND: Little is known about the changes in allergen sensitization in China secondary to the environmental variations over the past decade. We aimed at investigating the variations in sensitization among asthma and/or rhinitis patients in China between 2008 and 2018. METHODS: This study analyzed cross-sectional data from national surveys conducted in China in 2008 and 2018. After finishing the questionnaire, participants underwent serum specific IgE measurements. A total of 2322 and 2798 patients were enrolled in 2008 and 2018, respectively. The significance of differences in sensitization rates among four regions of China were assessed. Correlation analysis was used to identify the associations of sensitization with climate change and planting of Artemisia desertorum between the two surveys. RESULTS: Compared with 2008, the general sensitization rate to mites significantly increased in 2018, which ranked highest among all tested allergens. Sensitization to pollens, especially Artemisia vulgaris, showed the greatest increase in the north. The annual mean temperature, rainfall and relative humidity in all four regions, and the Artemisia desertorum coverage in the northeastern area, increased significantly in 2018 as compared with 2008. From 2008 to 2018, an increase in Dermatophagoides pteronyssinus sensitization was significantly associated with an increase in relative humidity (r = 0.54, p = 0.037). The increase in A. vulgaris sensitization was significantly associated with the increase in the A. desertorum planting area (r = 0.67, p = 0.006) and with a decrease in rainfall (r = -0.59, p = 0.021). CONCLUSIONS: House dust mites remain the most important allergen in Chinese individuals with asthma and/or rhinitis. Pollen sensitization dramatically increased in northern China. Increases in sensitization to dust mites and Artemisia were related to the increases in humidity and planting area of A. desertorum.
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Crown roots are essential for plants to obtain water and nutrients, perceive environmental changes, and synthesize plant hormones. In this study, we identified and characterized short crown root 8 (scr8), which exhibited a defective phenotype of crown root and vegetative development. Temperature treatment showed that scr8 was sensitive to temperature and that the mutant phenotypes were rescued when grown under low temperature condition (20 °C). Histological and EdU staining analysis showed that the crown root formation was hampered and that the root meristem activity was decreased in scr8. With map-based cloning strategy, the SCR8 gene was fine-mapped to an interval of 126.4 kb on chromosome 8. Sequencing analysis revealed that the sequence variations were only found in LOC_Os08g14850, which encodes a CC-NBS-LRR protein. Expression and inoculation test analysis showed that the expression level of LOC_Os08g14850 was significantly decreased under low temperature (20 °C) and that the resistance to Xanthomonas oryzae pv. Oryzae (Xoo) was enhanced in scr8. These results indicated that LOC_Os08g14850 may be the candidate of SCR8 and that its mutation activated the plant defense response, resulting in a crown root growth defect.
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Organogênese Vegetal/genética , Oryza/genética , Doenças das Plantas/genética , Proteínas de Plantas/genética , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas/genética , Mutação/genética , Oryza/crescimento & desenvolvimento , Oryza/microbiologia , Fenótipo , Doenças das Plantas/microbiologia , Plantas Geneticamente Modificadas/genética , Temperatura , Xanthomonas/genética , Xanthomonas/patogenicidadeRESUMO
BACKGROUND: Allergic rhinitis (AR) is a common allergic disease. It affects people worldwide and traditional Chinese medicine is becoming popular among AR patients because it has a definite clinical effect and there are few adverse reactions. Lung qi deficiency and cold syndrome (LQDCS) is a frequent type of AR, and the Chinese herbal medicine bimin decoction (BMD) is prescribed for it. This study compared the clinical efficacy of BMD for AR patients with LQDCS to the conventional medicine loratadine and fluticasone nasal spray. METHODS: The study was an open-label non-inferiority randomized controlled trial. A total of 108 AR patients with LQDCS aged 19 to 60 were randomly allocated in a 1:1 ratio to the BMD group or the control group by the central computer system in Beijing Hospital of Traditional Chinese Medicine from January 2017 to April 2018. In total, 98 participants completed the study (BMD group n = 51 and control group n = 47). Patients in the BMD group received BMD while those in the control group received fluticasone nasal spray and loratadine tablets for 4 weeks. The primary outcome was the change in the Total Nasal Symptom Score (TNSS) between the baseline and the end of treatment. Changes in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal resistance, and acoustic rhinometry parameters were secondary outcomes. All side effects due to the treatments were recorded. RESULTS: After the 4-week treatment, the total TNSS was significantly reduced in both groups compared to the baseline (P < 0.05). No significant between-groups differences were observed for changes in TNSS scores [- 0.298 (95% confidence interval -0.640 to 0.140)], which was within the defined non-inferiority margin. RQLQ in both groups decreased significantly (P < 0.001) from baseline, though a more obvious reduction was observed for the BMD group (P < 0.001). There were no significant differences in nasal resistance, nasal volume, or nasal minimum cross-sectional area between groups after treatment (P > 0.05). CONCLUSIONS: These findings indicate that BMD helps relieve the symptoms of perennial AR and improves rhinitis-related quality of life. Our study indicates that BMD is non-inferior to loratadine tablets and fluticasone nasal spray for AR patients with LQDCS. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-16010063. Registered on 2 December 2016.
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Antialérgicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Fluticasona/uso terapêutico , Loratadina/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Adulto , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obstrução Nasal , Sprays Nasais , Qualidade de Vida , Espirro/efeitos dos fármacos , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Allergen-specific immunotherapy (AIT) is an effective treatment for allergic rhinitis (AR). During the course of AIT, many biomarkers in body fluids change. It is necessary to find effective indicators of AIT. OBJECTIVE: To examine levels of salivary immunoglobulin A, E, and G4 (IgA, IgE, and IgG4, respectively) specific to Dermatophagoides pteronyssinus (Dp-IgA, Dp-IgE, and Dp-IgG4, respectively) and their changes in AR patients undergoing subcutaneous immunotherapy (SCIT). METHODS: This study included 82 patients with AR sensitized only to Dp and 14 healthy controls. Among patients with AR, 30 patients were not treated with specific immunotherapy (group A), while the remainder (n = 52) received house dust mite SCIT in the up-dosing phase (n = 27; group B) or the maintenance treatment phase (n = 25; group C). Dp-IgA, Dp-IgE, and Dp-IgG4 levels in the saliva were measured using the enzyme-linked immunosorbent assay. Clinical symptoms, concomitant medication, and the Rhinoconjunctivitis Quality of Life Questionnaire score were recorded and correlated with immunoglobulin levels. RESULTS: Salivary Dp-IgG4 and Dp-IgA levels were significantly lower in AR patients than in healthy controls ( P < .001 for both), while Dp-IgE levels were significantly higher ( P < .001). SCIT resulted in sustained increases in Dp-IgG4 and Dp-IgA in the maintenance phase compared to the up-dosing phase ( P < .001 for both), whereas Dp-IgE only increased in the up-dosing phase ( P = .004, P < .0125). There was no correlation between the different salivary immunoglobulins and clinical scores during SCIT. CONCLUSIONS: This study shows that allergen-specific IgE levels are increased in the saliva of sensitized patients, suggesting that measuring salivary IgE testing should be further considered for the diagnosis of AR. Moreover, allergen-specific IgA and IgG4 in the saliva, which may play protective roles against allergy, may serve as objective indicators for evaluating treatment response to SCIT. However, none of the immunoglobulin reflects subjective symptoms.
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Antígenos de Dermatophagoides/uso terapêutico , Biomarcadores/metabolismo , Dessensibilização Imunológica/métodos , Imunoglobulina A/metabolismo , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Rinite Alérgica/terapia , Saliva/metabolismo , Adolescente , Adulto , Idoso , Animais , Antígenos de Dermatophagoides/imunologia , Criança , Dermatophagoides pteronyssinus/imunologia , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Rinite Alérgica/imunologia , Adulto JovemRESUMO
OBJECTIVE: To show that Stat3 played a key role in the G1 to S phase transition in laryngocarcinoma cells. METHOD: Human laryngocarcinoma cell lines Hep-2 were transfected with Stat3 antisense oligonucleotide mediated by liposome, MTT assay was used to measure the proliferation, flow cytometry was applied to analyze the cell cycle, and the expressions of Stat3, phosphorylation specific Stat3 (tyrosine705), CyclinD1, Cyclin E, CDK2, CDK4, CDK6, p21 and p27 were detected by western blot. RESULT: Hep-2 laryngocarcinoma cell lines expressed constitutively activated Stat3. Antisense oligonucleotide which directed blocked up the translation site resulted in growth inhibition, downregulation of Stat3, p-Stat3, Cyclins and CDKs, and upregulation of p21 and p27. CONCLUSION: Our findings suggested that Stat3 played an important role in the G1 to S phase transition in laryngocarcinoma cells, Stat3 orchestrated cell cycle by regulating the balance between CDK/Cyclin complex and CKI.
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Fase G1 , Neoplasias Laríngeas/metabolismo , Fase S , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Humanos , Neoplasias Laríngeas/patologia , Fator de Transcrição STAT3/genética , TransfecçãoRESUMO
OBJECTIVE: To evaluate the expression and clinical significance of Endostatin, vascular endothelial growth factor (VEGF) and fibroblast growth factor basic-2 (FGF-2) in the laryngeal squamous cell carcinoma (LSCC). METHODS: The expression of Endostatin, VEGF and FGF-2 in 50 specimens of LSCC, 40 specimens of para-carcinoma and 10 specimens of normal laryngeal tissues were examined by Flow cytometry. RESULTS: Compared with para-carcinoma and normal laryngeal tissues, the expression level and positive rate of Endostatin, VEGF, FGF-2 in LSCC were different in statistics (P < 0.05); the expression level and positive rate of endostatin, VEGF, FGF-2 in LSCC are obviously higher than those in para-carcinoma and normal laryngeal tissues. The expression level and positive rate of Endostatin, VEGF, FGF-2 were no difference in statistics between para-carcinoma and normal laryngeal tissues (P > 0.05). The expression level and positive rate of Endostatin, VEGF, FGF-2 in LSCC were associated with lymphoid metastasis and clinical stage, not associated with age, sex and clinical group. CONCLUSIONS: Endostatin, VEGF and FGF-2 play important role in the incidence, development and prognosis of the LSCC.
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Carcinoma de Células Escamosas/metabolismo , Endostatinas/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Neoplasias Laríngeas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PrognósticoRESUMO
OBJECTIVE: To study the mechanism of STAT3 antisense oligonucleotide (STAT3 AS-ON) in combination with DDP in the treatment of laryngeal cancer. METHODS: STAT3 AS-ON, DDP, or STAT3 AS-ON + DDP was added into culture media. The expression and phosphorylation levels of STAT3 protein in Hep-2 cells were measured by Western Blot. The expression of Cyclin D1 and Bcl-xL was also detected by Western Blot. The cell proliferation was assayed by methyl thiazolyl tetrazolium (MTT). Flow cytometry was performed to analyze the cell cycle and apoptosis. RESULTS: STAT3 was highly expressed and phosphorylated in Hep-2 cells. Transfection of STAT3 AS-ON suppressed the expression and phosphorylation levels of STAT3 protein. Forty-eight hours after transfection, the proliferation of Hep-2 cells was inhibited in a dose-dependent manner. Inhibitory effects appeared at 24 h after transfection of STAT3 AS-ON, and became more obvious after 36 h. Seventy-two hours after transfection, the rate of apoptosis in STAT3 AS-ON + DDP group, DDP group, STAT3 AS-ON group, STAT3 S-ON group, lipidosome group and control group was 32.9%, 13.5%, 28.1%, 3.2%, 2.4%, 1.8% respectively. After the treatment of Hep-2 cells with STAT3 AS-ON and DDP for 72 h, the ratio of G1 phase was up-regulated from 55.7% to 74.9%, while that of S phase was own-regulate from 33.6% to 6.9%. CONCLUSIONS: STAT3 AS-ON and DDP could suppress the growth of laryngeal cancer cells and induce significant apoptosis of laryngeal cancer cells. Combined use of them had a synergic effect, obviously inhibiting the activation of STAT3 signaling transduction pathway of laryngeal cancer cells. Selective inhibition of specific signaling pathway may provide a new therapeutic approach for treating laryngeal cancers.
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Carcinoma de Células Escamosas/metabolismo , Neoplasias Laríngeas/metabolismo , Oligonucleotídeos Antissenso/farmacologia , Fator de Transcrição STAT3/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Oligonucleotídeos Antissenso/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , TransfecçãoRESUMO
OBJECTIVE: To investigate the expression of STAT3 and P-STAT3 and the relationship between P-STAT3 and various clinical pathological characteristics in human laryngeal carcinoma. METHOD: The expression of STAT3 and its activated form P-STAT3 in tumor tissues from 50 radically resected specimens of laryngeal carcinoma and 10 normal laryngeal tissues was detected by immunohistochemical staining. RESULT: The rate of protein expression of STAT3 and P-STAT3 in laryngeal carcinoma were 36/50 (72.0%) and 29/50 (58.0%) respectively, which were significantly higher than that in normal group (P < 0.01). The positive rate of P-STAT3 was closely related to the clinical stage and lymph node metastasis (P < 0.05). The expression STAT3 in laryngeal carcinoma was located in the cytoplasm of carcinoma cells, while P-STAT3 was located in the cell nucleus. CONCLUSION: STAT3 and PSTAT3 were overexpressed in human laryngeal carcinoma. Activation of STAT3 was significantly related to the clinical stage and lymph node metastasis. The expression of STAT3 can be used as a significant parameter in predicting the biological behaviour of laryngeal carcinoma.