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BACKGROUND: Neonates with immature auditory function (eg, weak/absent middle ear muscle reflex) could conceivably be vulnerable to noise-induced hearing loss; however, it is unclear if neonates show evidence of hearing loss following MRI acoustic noise exposure. PURPOSE: To explore the auditory effects of MRI acoustic noise in neonates. STUDY TYPE: Prospective. SUBJECTS: Two independent cohorts of neonates (N = 19 and N = 18; mean gestational-age, 38.75 ± 2.18 and 39.01 ± 1.83 weeks). FIELD STRENGTH/SEQUENCE: T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, single-shot echo-planar imaging-based diffusion-tensor imaging, single-shot echo-planar imaging-based diffusion-kurtosis imaging and T2-weighted fluid-attenuated inversion recovery sequence at 3.0 T. ASSESSMENT: All neonates wore ear protection during scan protocols lasted ~40 minutes. Equivalent sound pressure levels (SPLs) were measured for both cohorts. In cohort1, left- and right-ear auditory brainstem response (ABR) was measured before (baseline) and after (follow-up) MRI, included assessment of ABR threshold, wave I, III and V latencies and interpeak interval to determine the functional status of auditory nerve and brainstem. In cohort2, baseline and follow-up left- and right-ear distortion product otoacoustic emission (DPOAE) amplitudes were assessed at 1.2 to 7.0 kHz to determine cochlear function. STATISTICAL TEST: Wilcoxon signed-rank or paired t-tests with Bonferroni's correction were used to compare the differences between baseline and follow-up ABR and DPOAE measures. RESULTS: Equivalent SPLs ranged from 103.5 to 113.6 dBA. No significant differences between baseline and follow-up were detected in left- or right-ear ABR measures (P > 0.999, Bonferroni corrected) in cohort1, or in DPOAE levels at 1.2 to 7.0 kHz in cohort2 (all P > 0.999 Bonferroni corrected except for left-ear levels at 3.5 and 7.0 kHz with corrected P = 0.138 and P = 0.533). DATA CONCLUSION: A single 40-minute 3-T MRI with equivalent SPLs of 103.5-113.6 dBA did not result in significant transient disruption of auditory function, as measured by ABR and DPOAE, in neonates with adequate hearing protection. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 5.
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This study aimed to investigate the protective effects of PPARγ/CPT-1 regulation on cisplatin-induced cochlear hair cell injury. The viability, apoptosis and mitochondrial membrane potential of cisplatin-induced HEI-OC1 cells were determined by CCK-8 assay, TUNEL and JC-1 staining, respectively. The oxidative stress and lipid metabolism were detected by the assay kits of MDA, ROS, SOD, CAT, TG and FFA. The transfection efficiency of overexpression (OV)-PPARG and OV-CPT1A was examined by RT-qPCR and the expressions of apoptosis- and lipid metabolism-related proteins were detected by western blot. As a result, cisplatin with varying concentrations (5, 10, 30 µM) suppressed the viability, promoted the apoptosis and hindered the mitochondrial function of HEI-OC1 cells, accompanied with up-regulated expressions of Bax and cleaved caspase-3 and down-regulated expression of Bcl-2. The oxidative stress was aggravated and lipid metabolism was inhibited by cisplatin (5, 10, 30 µM) induction, evidenced by the increased levels of MDA, ROS, TG, FFA and the decreased levels of SOD and CAT. Overexpression of PPARG or CPT1A could improve the viability, mitochondrial function, lipid metabolism and suppress the oxidative stress and apoptosis of cisplatin-induced HEI-OC1 cells. In conclusion, up-regulation of PPARG or CPT1A ameliorated cochlear hair cell injury by improving cellular lipid metabolism and inhibiting oxidative stress.
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Cisplatino , PPAR gama , Apoptose/genética , Cisplatino/farmacologia , Células Ciliadas Auditivas/metabolismo , Metabolismo dos Lipídeos/genética , Estresse Oxidativo/genética , PPAR gama/genética , PPAR gama/metabolismo , PPAR gama/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Carnitina O-Palmitoiltransferase/metabolismoRESUMO
Background: Thyroid cancer is the most common endocrine malignancy and the fastest growing cancer worldwide. Thyroid cancer has the largest genetic component of all cancers. Previous genome-wide association studies indicated that genetic polymorphism in PCNXL2 is related to thyroid cancer susceptibility in European populations. This study aims to determine the influence of PCNXL2 polymorphisms on thyroid cancer risk in Chinese individuals. Methods: This case-control study identified four polymorphisms in PCNXL2 among 510 thyroid cancer cases and 509 healthy controls. The associations of PCNXL2 polymorphisms with thyroid cancer susceptibility were detected by calculating odds ratios. Multifactor dimensionality reduction was performed to detect the impact of SNP (single nucleotide polymorphism)-SNP interactions on the risk of thyroid cancer. Results: The study showed that rs10910660 in PCNXL2 was related to thyroid cancer susceptibility. Rs12129938 played a protective role in thyroid cancer susceptibility. Stratification analysis indicated that rs10910660 increased thyroid cancer risk at age >45 years. Rs12129938 enhanced susceptibility to thyroid cancer at age >45 years, while this SNP decreased thyroid cancer risk at age ≤45 years. Rs4649295 was associated with lower susceptibility to thyroid cancer at age ≤45 years. An association was observed between rs6424270 and rs12129938 with decreased susceptibility to thyroid cancer in women. Rs10910660 was related to thyroid cancer risk in men. The combination of rs6424270, rs10910660, rs12129938 and rs4649295 was the best model to predict thyroid cancer. Conclusion: This study suggests that PCNXL2 polymorphisms are risk factors for thyroid cancer in the Chinese population.
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Predisposição Genética para Doença , Neoplasias da Glândula Tireoide/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Estudo de Associação Genômica Ampla , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Proteção , Fatores de Risco , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologiaRESUMO
BACKGROUND: Laryngeal carcinoma (LC) is one of common diagnosed head and neck malignancies. Telomere length has been reported involved in malignant transformation and tumorigenesis. We speculate that single nucleotide polymorphisms (SNPs) in telomere length-related gene oligonucleotide/oligosaccharide-binding folds containing 1 (OBFC1) may have an association with LC in Chinese Han male population. METHODS: To prove this hypothesis, we performed a case-control study to analyze the OBFC1 polymorphisms in 172 LC patients and 180 healthy controls. A total of five SNPs (i.e., rs9325507, rs3814220, rs12765878, rs11191865, rs9420707) were selected for further genotyping. RESULTS: There was a significant difference in rs9325507 T allele frequency (OR = 0.88, 95% CI 0.64-1.21, P = 0.036) and rs11191865 A allele frequency (OR = 0.86, 95% CI 0.62-1.18, P = 0.009) between patient and control groups. In addition, the rs9325507 T/C genotype, rs3814220 G/A genotype, rs12765878 C/T genotype and rs11191865 A/G genotype had a lower risk of LC based on the results of logistic regression model analysis. CONCLUSIONS: The results indicate a potential association between OBFC1 and LC risk in Chinese Han male population. Further work is required to confirm these results and explore the mechanisms of these effects.
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Neoplasias Laríngeas/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a Telômeros/genética , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Humanos , Neoplasias Laríngeas/mortalidade , Masculino , Pessoa de Meia-IdadeRESUMO
This study examined the association between hector battifora mesothelial antigen-1 (HBME-1) expression and papillary thyroid carcinoma (PTC). A total of 206 patients were enrolled in the current study including 96 PTC patients and 110 patients with benign thyroid nodules (BTN). Immunohistochemistry (Envision) were performed to assess the expression of HBME-1. Receiver operating characteristic curve (ROC) curves were applied to evaluate the diagnostic tumor node metastasis (TNM) value of HBME-1. Specimens from 96 patients with PTC and 110 patients with BTC were reviewed. HBME-1 was positively immunostained in PTC tissue, which was significantly higher than that in BTN tissues (77.1 vs. 5.77 %, P < 0.05). Immunohistochemistry also identified that HBME-1 expression did not show any statistically significant differences based on gender, age, tumor size, TNM stage, and lymph node metastasis (P > 0.05). Importantly, HBME-1 expression was correlated with infiltration levels and differential levels in PTC (both P < 0.05). HBME-1 was found to have high sensitivity (94.5 %) and specificity (77.08 %) for PTC diagnosis. Moreover, HBME-1 had a high specificity (83.33 %) at identifying the differential levels of PTC, but a low sensitivity (22.92 %). The sensitivity and specificity of HBME-1 identifying the infiltration levels of PTC were, respectively, 72.70 and 72.00 %. HBME-1 was highly expressed in PTC tissues, and HBME-1 can serve as a potential biomarker in the diagnosis of PTC.
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Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Carcinoma/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/metabolismo , Adolescente , Adulto , Carcinoma/patologia , Carcinoma Papilar , Feminino , Humanos , Imuno-Histoquímica/métodos , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/metabolismo , Nódulo da Glândula Tireoide/patologia , Adulto JovemRESUMO
Objective:To explore the clinical value of supine median³ nystagmus in the accurate diagnosis of horizontal semicircular canal benign paroxysmal positional vertigoï¼HC-BPPVï¼. Methods:A total of 187 patients with HC-BPPV admitted to the First Affiliated Hospital of Xi'an Jiaotong University from June 2020 to March 2021 were selected. Among them 42 cases of Cupulolithiasis and 145 cases of Canalithiasis. The nystagmus parameters of patients left and right supine position and supine median³ position were recorded in detail by RART. According to the direction of supine median³ nystagmus, patients were divided into three groups: group Aï¼nystagmus to weak sideï¼, group Bï¼nystagmus to strong sideï¼, group Cï¼negative nystagmusï¼. The canalith repositioning manoeuvresï¼CRMï¼ was carried out by utility of an automatic vestibular function diagnosis and therapy systemï¼SRM-IVï¼. The cure rate of CRM in three groups of HC-BPPV patients was compared, Multivariate logistic regression analysis was performed to analyze the influencing factors of CRM for HC-BPPV. Results:The cure rates of group A, group B and group C were 81.58%, 16.13% and 56.25%, respectively. The difference among the three groups was statistically significant. Then a pairwise comparison of group A, B and C, the difference was statistically significantï¼χ²A-B=40.294,P<0.001,χ²B-C=14.528, P<0.001,χ²A-C=11.606, P=0.001ï¼; the results of multivariate logistic regression analysis showed that the direction of supine median³ nystagmus and BMI were the influencing factors of CRM for HC-BPPV. Conclusion:The direction, intensity and duration of supine median³ nystagmus play an important role in determining the responsibility semicircular canal of HC-BPPV.
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Vertigem Posicional Paroxística Benigna , Canais Semicirculares , Humanos , Vertigem Posicional Paroxística Benigna/diagnóstico , Vertigem Posicional Paroxística Benigna/terapia , Feminino , Masculino , Canais Semicirculares/fisiopatologia , Decúbito Dorsal , Nistagmo Patológico/diagnóstico , Pessoa de Meia-Idade , Testes de Função Vestibular/métodos , Adulto , Modelos LogísticosRESUMO
Cisplatin, which is effective for the treatment of solid tumors, also can induce cochlear hair cell damage. Therefore, this study was intended to explore how Hippo/YAP signaling pathway affects the cochlear hair cell injury by regulating ferroptosis. After cisplatin induction, or LAT1-IN-1 (YAP activator) and verteporfin (YAP inhibitor) treatment or transfection, the viability of HEI-OC1 cells was detected by cell counting kit-8 (CCK-8) assay. The iron level and the levels of oxidative stress markers (ROS, MDA and 4-HNE) were analyzed by iron assay kit, reactive oxygen species (ROS), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) assay kits, respectively. The expression of ferritin light chain (FTL) in HEI-OC1 cells was detected by immunofluorescence and protein expressions of yes associated protein (YAP,) phosphorylated YAP (p-YAP), transferrin receptor (TFRC), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) in HEI-OC1 cells were detected by western blot. The transcription of FTL and TFRC by YAP1 was verified by dual-luciferase reporter assay. The transfection efficiency of small interfering RNA (si-RNA) specific to FTL (siRNA-FTL) and TFRC (siRNA-TFRC) was confirmed by reverse transcriptionquantitative polymerase chain reaction (RTqPCR). As a result, cisplatin inhibited the viability of HEI-OC1 cells by increasing free Fe2+ level and decreasing FTL level. LAT1-IN-1 promoted the viability of cisplatin-induced HEI-OC1 cells by suppressing oxidative stress level, free Fe2+ level, ferroptosis and increasing FTL level, while the effect of verteporfin was the opposite. YAP1 transcriptionally regulated the expression of FTL and TFRC. Inhibition of FTL suppressed the viability of cisplatin-induced HEI-OC1 cells by increasing oxidative stress level, free Fe2+ level, ferroptosis and decreasing FTL level, while the effect of TFRC inhibition was the opposite. In conclusion, YAP1 ameliorated cochlear hair cell injury by upregulating FTL and TFRC to suppress ferroptosis.
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Cisplatino , Ferroptose , Cisplatino/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Verteporfina/farmacologia , Verteporfina/metabolismo , Apoptose , Células Ciliadas Auditivas , RNA Interferente Pequeno/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Thyroid cancer is the most common malignancy of the endocrine system. Circular RNA (circRNA) is recognized as a key regulator of tumorigenesis in papillary thyroid carcinoma (PTC). Here this work focused on the mechanism of circRNA_0003892 (circ_0003892) in PTC progression. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine circ_0003892, microRNA-326 (miR-326) and LIM and SH3 protein 1 (LASP1) mRNA expression levels in PTC tissues and cell lines. Besides, cell counting kit-8 (CCK-8), EdU and transwell assays were conducted to detect the proliferative, migrative and invasive abilities of PTC cells, respectively. B The targeting relationships between miR-326 and circ_0003892 or LASP1 3'-UTR were verified by dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0003892 expression was raised in PTC tissues and cells, which was significantly interrelated with larger tumor size and extrathyroidal extension in PTC sufferers. Overexpression of circ_0003892 significantly promoted the malignant biological behaviors of PTC cells. Additionally, miR-326 was a downstream target of circ_0003892, and miR-326 overexpression weakened the promoting effect of circ_0003892 overexpression on the malignant progression of PTC. MiR-326 specifically inhibited LASP1. Circ_0003892 positively regulated LASP1 expression by targeting miR-326. CONCLUSION: Circ_0003892 up-regulates LASP1 expression and facilitates PTC progression via competitively binding to miR-326.
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MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , RNA Circular/genética , Neoplasias da Glândula Tireoide/genética , Carcinogênese , MicroRNAs/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Proteínas do Citoesqueleto , Proteínas Adaptadoras de Transdução de Sinal , Proteínas com Domínio LIM/genéticaRESUMO
Objective:To evaluate the influence of an additional roll test on the repositioning procedure by SRM-vertigo diagnosis system for horizontal canal benign paroxysmal positional vertigoï¼HC-BPPVï¼. Methods:A total of 713 patients diagnosed with HC-BPPV in Department of Otolaryngology Head and Neck Surgeryï¼the First Affiliated Hospital of Xi'an Jiaotong University from Jan 2020 to Feb 2022 were enrolled. The patients were divided into two groups by hospital card numbers, in which the number is odd were considered as group A, and the number is even were considered as group B. The group A underwent two circles of Barbecue repositioning procedure by SRM-vertigo diagnosis system, while the group B first performed an additional roll test and then underwent two circles of Barbecue repositioning procedure by SRM-vertigo diagnosis system, to observe the cure rate and compare influence of HC-BPPV by an additional roll test. The quality of life and sleep of patients before and one-month after the treatment were assessed by the dizziness handicap inventoryï¼DHIï¼ and the pittsburgh sleep qualityï¼PSQIï¼. Results:The cure rate of group A was 63.21%, and the cure rate of group B was 87.68%ï¼the difference between the two groups was statistically significantï¼P<0.05ï¼; The DHI score of patients after the repositioning was significantly lower than that before the repositioningï¼P<0.05ï¼. The PSQI score after the repositioning was significantly lower than that before the repositioningï¼P<0.05ï¼. The DHI and the PSQI scores after the repositioning were significantly lower than that before the repositioning, with a statistically significant difference ï¼P< 0.05ï¼. The total score of DHI in group B after treatment was lower than that in group A, with a statistically significant differenceï¼P<0.05ï¼. The total score of PSQI in group B after treatment was lower than that in group A, with non-statistically significant difference ï¼P< 0.05ï¼. Conclusion:An additional roll test before the repositioning procedure by SRM-vertigo diagnosis system can significantly improve the cure rate of HC-BPPV, relieve anxiety, and improve the quality of life.
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Vertigem Posicional Paroxística Benigna , Qualidade de Vida , Humanos , Vertigem Posicional Paroxística Benigna/diagnóstico , Posicionamento do Paciente/métodos , Tontura , Canais SemicircularesRESUMO
Background: Nucleotide excision repair (NER) is pivotal in the development of smoking-related malignancies. Nine core genes (XPA, XPB, XPC, XPD, XPF, XPG, ERCC1, DDB1, and DDB2) are highly involved in the NER process. We combined two phenotypes of NER pathway (NER protein and NER gene mRNA expression) and evaluated their associations with the risks of the head and neck squamous cell carcinomas (HNSCCs) in a Chinese population. Methods: We conducted a case-control study of 337 HNSCC patients and 285 cancer-free controls by measuring the expression levels of nine core NER proteins and NER gene mRNA in cultured peripheral lymphocytes. Results: Compared with the controls, cases had statistically significantly lower protein expression levels of XPA (P < 0.001) and lower mRNA expression levels of XPA and XPB (P = 0.005 and 0.001, respectively). After dividing the subjects by controls' medians of expression levels, we found an association between increased risks of HNSCCs and low XPA protein level (P trend = 0.031), as well as low mRNA levels of XPA and XPB (P trend = 0.024 and 0.001, respectively). Subsequently, we correlated the two phenotypes and found associations between the NER mRNA and protein levels. Finally, the sensitivity of the expanded model with protein and mRNA expression levels, in addition to demographic variables, on HNSCCs risk was significantly improved. Conclusions: Combining two phenotypes of NER pathway may be more effective than the model only including one single phenotype for the assessment of risks of HNSCCs.
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Reparo do DNA , Neoplasias de Cabeça e Pescoço , Estudos de Casos e Controles , China , Neoplasias de Cabeça e Pescoço/genética , Humanos , Fenótipo , RNA Mensageiro/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
Laryngeal squamous cell carcinoma (LSCC) is an aggressive malignancy with highly mortality rate. Long non-coding RNA (lncRNA) AGAP2-AS1 is an identified oncogene in several types of cancers. However, the role of AGAP2-AS1 in LSCC remains unclear. The expression levels of AGAP2-AS1 in LSCC tissues and cell lines were measured using qRT-PCR. AGAP2-AS1 was knocked down in LSCC cells through transfection with siRNA-AGAP2-AS1. Cell proliferation and invasion were detected using MTT and transwell assays. Dual-luciferase reporter gene assay was performed to confirm the interaction with AGAP2-AS1 and downstream genes. Our results showed that AGAP2-AS1 expression was remarkably increased in human LSCC tissues and cell lines. Knockdown of AGAP2-AS1 significantly inhibited the proliferation and invasion of LSCC cells. In addition, AGAP2-AS1 sponged miR-193a-3p and regulated its expression in LSCC cells. Inhibition of miR-193a-3p reversed the effects of AGAP2-AS1 knockdown on LSCC cells. Furthermore, Lysyl oxidase-like 4 (LOXL4) was a target gene of miR-193a-3p and the role of miR-193a-3p was mediated by LOXL4. In conclusion, these findings suggest that knockdown of AGAP2-AS1 inhibited the proliferation and invasion of LSCC cells through regulating the miR-193a-3p/LOXL4 axis.
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Neoplasias de Cabeça e Pescoço , MicroRNAs , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína-Lisina 6-Oxidase/genética , Proteína-Lisina 6-Oxidase/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumors in the world. Genetic variants have an important role in HNSCC progression. Our study is aimed at exploring the relationship between MIR17HG polymorphisms and HNSCC risk in the Chinese Han population. METHODS: We recruited 537 HNSCC cases and 533 healthy subjects to detect the correlation of six polymorphisms in MIR17HG with HNSCC susceptibility. The associations were evaluated by computing odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression analysis. RESULTS: Our study revealed that rs7336610 (OR 1.77, 95%CI = 1.09-2.86, and p = 0.021) and rs1428 (OR 1.73, 95%CI = 1.07-2.81, and p = 0.025) are strongly associated with increased susceptibility to HNSCC in men. Besides, rs17735387 played a crucial protective role in stage III/IV HNSCC patients (OR 0.34, 95%CI = 0.12-0.95, and p = 0.040) compared with stage I/II. CONCLUSION: Our study firstly indicated that MIR17HG polymorphisms are significantly associated with HNSCC susceptibility, which suggests that MIR17HG has a potential role in the occurrence of HNSCC.
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Povo Asiático/genética , Etnicidade/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Frequência do Gene/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Probabilidade , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
BACKGROUND: Papillary thyroid cancer (PTC) is the cardinal histologic type of thyroid cancer, which is the most prevalent kind of endocrine malignancy. The expression of IL-6 is found higher in thyroid carcinoma (THCA) samples than paired normal tissues based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue expression (GTEx) database. In this study, we aimed to investigate the association between interleukin-6 (IL-6) polymorphisms and the PTC risk. METHODS: A case-control study was designed using the following data: 241 PTC patients and 463 healthy controls. Five single nucleotide polymorphisms (SNPs) in IL-6 were selected and genotyped using Agena MassARRAY technology. RESULTS: Our results revealed that SNP rs1800796 was associated with an increased PTC risk in co-dominant model (p = 0.042) and dominant model (p = 0.027). Rs1524107 was also a risk factor for PTC susceptibility in co-dominant model (p = 0.003), dominant model (p = 0.002) and log-additive model (p = 0.044). Moreover, rs2066992 significantly increased the PTC risk in co-dominant model and dominant model (p = 0.011, p = 0.009, respectively). Additionally, rs2069837 variant elevated the PTC risk based on dominant model (p = 0.041). In silico analysis, GTEx results for rs1800796, rs1524107 and rs2066992 variants are known to be associated with IL-6 gene expression. Using HaploReg, we found rs1800796, rs1524107 and rs2066992 in LD with functional importance. CONCLUSION: Our study indicates that IL-6 variants may be a risk factor involved in the pathogenesis and development of PTC.
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Predisposição Genética para Doença , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Câncer Papilífero da Tireoide/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de RiscoRESUMO
The original version of this Article contained errors in the author affiliations. Affiliation 2 incorrectly read 'Department of Neurology, The First Hospital of Jilin University, Changchun 130021 Jilin Province, China.'Affiliation 5 incorrectly read 'Department of Otolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061 Shanxi Province, China'Affiliation 9 incorrectly read 'State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.'This has now been corrected in both the PDF and HTML versions of the Article.
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A definitive pre-mortem diagnosis of prion disease depends on brain biopsy for prion detection currently and no validated alternative preclinical diagnostic tests have been reported to date. To determine the feasibility of using skin for preclinical diagnosis, here we report ultrasensitive serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC) assays of skin samples from hamsters and humanized transgenic mice (Tg40h) at different time points after intracerebral inoculation with 263K and sCJDMM1 prions, respectively. sPMCA detects skin PrPSc as early as 2 weeks post inoculation (wpi) in hamsters and 4 wpi in Tg40h mice; RT-QuIC assay reveals earliest skin prion-seeding activity at 3 wpi in hamsters and 20 wpi in Tg40h mice. Unlike 263K-inoculated animals, mock-inoculated animals show detectable skin/brain PrPSc only after long cohabitation periods with scrapie-infected animals. Our study provides the proof-of-concept evidence that skin prions could be a biomarker for preclinical diagnosis of prion disease.
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Bioensaio/métodos , Proteínas PrPSc/análise , Scrapie/diagnóstico , Pele/patologia , Animais , Anticorpos Monoclonais/imunologia , Biomarcadores/análise , Encéfalo/patologia , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Humanos , Mesocricetus , Camundongos , Camundongos Transgênicos , Proteínas PrPSc/imunologia , Proteínas PrPSc/patogenicidade , Scrapie/patologiaRESUMO
As an important metabolic enzyme, it is necessary to investigate the genetic polymorphisms of CYP2J2 among healthy Tibetan individuals. Genetic polymorphisms of CYP2J2 could affect enzyme activity and lead to differences among individual responses to drugs.We sequenced the whole gene of CYP2J2 in 100 unrelated, healthy Tibetan volunteers from the Tibet Autonomous Region and screened for genetic variants in the promoters, introns, exons, and the 3'-UTR regions.We detected 4 novel genetic polymorphisms of the CYP2J2 gene. The allelic frequencies of CYP2D6*1 and *7 were 0.955 and 0.045, respectively. CYP2D6*1/*7 decreased the activity of CYP2J2 and was expressed in 9% of the sample population.Our results provided basic data about CYP2J2 polymorphisms in a Tibetan population, suggested that the enzymatic activities of CYP2J2 might be different within the ethnic group, and offered a theoretical basis for individualized medical treatment and drug genomics studies.
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Sistema Enzimático do Citocromo P-450/genética , Etnicidade/genética , Regiões 3' não Traduzidas , Citocromo P-450 CYP2J2 , Éxons , Feminino , Frequência do Gene , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Tibet/epidemiologiaRESUMO
Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is transmissible through iatrogenic routes due to abundant infectious prions [misfolded forms of the prion protein (PrPSc)] in the central nervous system (CNS). Some epidemiological studies have associated sCJD risk with non-CNS surgeries. We explored the potential prion seeding activity and infectivity of skin from sCJD patients. Autopsy or biopsy skin samples from 38 patients [21 sCJD, 2 variant CJD (vCJD), and 15 non-CJD] were analyzed by Western blotting and real-time quaking-induced conversion (RT-QuIC) for PrPSc Skin samples from two patients were further examined for prion infectivity by bioassay using two lines of humanized transgenic mice. Western blotting revealed dermal PrPSc in one of five deceased sCJD patients and one of two vCJD patients. However, the more sensitive RT-QuIC assay detected prion seeding activity in skin from all 23 CJD decedents but not in skin from any non-CJD control individuals (with other neurological conditions or other diseases) during blinded testing. Although sCJD patient skin contained ~103- to 105-fold lower prion seeding activity than did sCJD patient brain tissue, all 12 mice from two transgenic mouse lines inoculated with sCJD skin homogenates from two sCJD patients succumbed to prion disease within 564 days after inoculation. Our study demonstrates that the skin of sCJD patients contains both prion seeding activity and infectivity, which raises concerns about the potential for iatrogenic sCJD transmission via skin.
Assuntos
Síndrome de Creutzfeldt-Jakob/patologia , Príons/patogenicidade , Pele/patologia , Idoso , Animais , Bioensaio , Encéfalo/patologia , Modelos Animais de Doenças , Feminino , Humanos , Técnicas In Vitro , Masculino , Camundongos Transgênicos , Pessoa de Meia-Idade , Doenças Priônicas/patologiaRESUMO
Prion protein (PrP) has proven to bind amyloid beta (Aß) oligomers with high affinity, changing our understanding of both prion diseases (PD) and Alzheimer's disease (AD) at the molecular and phenotypic levels, although the latter currently lacks sufficient attentions. Transgenic mice expressing anchorless PrP developed unusual diseases reminiscent of AD with tremendous amyloid plaque formation. In this review, we described two interesting observations at the phenotypic level. First, common pathogenic mutations of the PRNP gene in Gerstmann-Sträussler-Scheinker (GSS) syndrome were clustered at PrP95-105. Meanwhile, all nonsense PRNP mutations that generated soluble PrP 95-105 exhibited phenotypes with abundant amyloid formations. We speculate that PrP-Aß oligomers binding might be the underlying mechanism of the predominant amyloid phenotypes. Second, soluble PrP-Aß oligomer complexes might exist in the extracellular space at the beginning of both PD and AD and subserve an initial neuroprotective function. Thus, the diseases would only present after long-term accumulation. This might be the central common pathogenic event of both PD and AD.