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1.
Future Oncol ; 16(25): 1911-1920, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32615044

RESUMO

Aim: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. This study aimed to investigate the role of long noncoding RNA THOR in CRC. Materials & methods: The expression of THOR in 103 cases of CRC tissues and four CRC cell lines was examined by quantitative real-time PCR. Cell counting kit-8 and colony formation assays were applied to detect cell proliferation, and flow cytometry was used for testing cell cycle and apoptosis of CRC. Results: We found that THOR was highly expressed in CRC and correlated with tumor node metastasis stage, histological subtype, tumor size and differentiation and survival in CRC patients. Meanwhile, knockdown of THOR significantly suppressed cell proliferation and cell cycle of CRC, whereas promoted cell apoptosis. Conclusion: Our findings suggest that THOR is an oncogenic long noncoding RNA in CRC and a potential prognostic biomarker for this cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , Adulto , Idoso , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/diagnóstico , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Carga Tumoral
2.
Biochem Biophys Res Commun ; 499(4): 913-919, 2018 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-29626476

RESUMO

Long non-coding RNA (LncRNA) dysregulation is associated with human osteosarcoma (OS) cell progression. Recent studies have characterized a novel but ultra-conserved LncRNA THOR ("Lnc-THOR") as a cancer-specific LncRNA, mediating cell growth. In the current study, we show that Lnc-THOR is expressed in established and primary human OS cells. It is also detected in human OS tissues, but not in the surrounding normal bone tissues. siRNA-induced knockdown or CRSIPR/Cas9-mediated knockout Lnc-THOR significantly inhibited human OS cell survival and proliferation. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) target mRNAs, including IGF2, GLI1 and CD44, were downregulated in Lnc-THOR-silenced OS cells as well. Conversely, forced over-expression of Lnc-THOR enhanced IGF2BP1 target mRNA expression, promoting OS cell survival and proliferation. In vivo, xenograft tumors of Lnc-THOR-knockout U2OS cells grew significantly slower than the control U2OS tumors. Together, these results show that Lnc-THOR expression is essential for human OS cell growth. Lnc-THOR could be a novel therapeutic target and/or diagnosis marker for human OS.


Assuntos
Osteossarcoma/genética , Osteossarcoma/patologia , RNA Longo não Codificante/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Camundongos SCID , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo
3.
Biochem Biophys Res Commun ; 501(3): 661-667, 2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29752937

RESUMO

BACKGROUND: Recent studies have characterized a novel but extremely conserved long non-coding RNA (LncRNA) THOR. THOR directly associates with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to promote mRNA stabilization of key pro-cancerous genes. RESULTS: Here, we show that THOR is expressed in human renal cell carcinoma (RCC) tissues and established/primary human RCC cells. It was not detected in normal renal tissues nor in HK-2 and primary human renal epithelial cells. THOR silencing (by targeted siRNAs) or CRISPR/Cas9 knockout inhibited RCC cell growth, viability and proliferation in vitro. Reversely, forced over-expression of THOR promoted RCC cell survival and proliferation. IGF2BP1-regulated genes, including IGF2, GLI1 and Myc, were downregulated by THOR silencing or knockout, but they were upregulated after THOR over-expression. In vivo, THOR-knockout 786-O tumors grew significantly slower than the control tumors in nude mice. CONCLUSION: THOR expression promotes RCC cell growth in vitro and in vivo. THOR could be a novel and important therapeutic target for human RCC.


Assuntos
Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Animais , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Rim/metabolismo , Rim/patologia , Neoplasias Renais/patologia , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/genética , Células Tumorais Cultivadas
4.
Future Oncol ; 13(23): 2045-2051, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29019414

RESUMO

AIM: We explore the biomarker potential of the TERT hypermethylated oncologic region (THOR) in pancreatic cancer. MATERIALS & METHODS: We assessed the methylation status of THOR using the cancer genome atlas data on the cohort of pancreatic cancer (n = 193 patients). RESULTS: THOR was significantly hypermethylated in pancreatic tumor tissue when compared with the normal tissue used as control (p < 0.0001). Also, THOR hypermethylation could distinguish early stage I disease from normal tissue and was associated with worse prognosis. DISCUSSION:  We found that THOR is hypermethylated in pancreatic tumor tissue when compared with normal tissue and that THOR methylation correlates with TERT expression in tumor samples. CONCLUSION: Our preliminary findings support the diagnostic and prognostic values of THOR in pancreatic cancer.


Assuntos
Biomarcadores Tumorais , Metilação de DNA , Recidiva Local de Neoplasia/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Telomerase/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Pancreáticas/mortalidade , Prognóstico , Regiões Promotoras Genéticas
5.
Occup Med (Lond) ; 65(4): 296-302, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25883217

RESUMO

BACKGROUND: Accurate workplace injury data are useful in the prioritization of prevention strategies. In the UK, physicians report workplace ill-health data within The Health and Occupation Research (THOR) network, including injury case reports. AIMS: To compare workplace injury data reported by occupational physicians (OPs) and general practitioners (GPs) to THOR. METHODS: Injury cases reported by OPs and GPs, reported to THOR between 2006 and 2012 were analysed. Demographics, industrial groups, nature of injury, kind of accident and site of injury were compared. Data on sickness absence for workplace injuries reported by GPs were investigated. RESULTS: In total, 2017 workplace injury cases were reported by OPs and GPs. Males were more likely to sustain a workplace accident than females. Sprains and strains were reported most often, with the upper limbs being affected most frequently. Slips, trips and falls were identified as important causal factors by both OPs and GPs. Psychological injuries also featured in THOR reporting, with a higher proportion reported by OPs (21%) than by GPs (3%). The proportion of people classified as 'unfit' by GPs reduced following the introduction of the 'fit' note. CONCLUSIONS: THOR reports returned by OPs and GPs provide a valuable source of information of workplace injury data, and complement other sources of information, such as the Reporting of Injuries, Diseases and Dangerous Occurrences Regulations and the Labour Force Survey.


Assuntos
Clínicos Gerais/psicologia , Medicina do Trabalho/normas , Projetos de Pesquisa/normas , Local de Trabalho/estatística & dados numéricos , Ferimentos e Lesões , Feminino , Humanos , Indústrias/métodos , Indústrias/estatística & dados numéricos , Masculino , Medicina do Trabalho/métodos , Projetos de Pesquisa/tendências , Inquéritos e Questionários
7.
Stapp Car Crash J ; 67: 78-111, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38662622

RESUMO

THOR-AV 5F, a modified THOR-5F dummy, was designed to represent both upright and reclined occupants in vehicle crashworthiness studies. The dummy was evaluated in four test conditions: a) 25° seatback, 15 km/h, b) 25° seatback, 32 km/h, c) 45° seatback, 15 km/h, d) 45° seatback, 32 km/h. The dummy's biomechanical responses were compared against those of postmortem human subjects (PMHS) tested in the same test conditions. The latest National Highway Traffic Safety Administration (NHTSA) BioRank method was used to provide a biofidelity ranking score (BRS) for each data channel in the tests to assess the dummy's biofidelity objectively. The evaluation was categorized into two groups: restraint system and dummy. In the four test conditions, the restraint system showed good biofidelity with BRS scores of 1.49, 1.47, 1.15, and 1.79, respectively. The THOR-AV 5F demonstrated excellent biofidelity in three test conditions: 25° seatback, 15 km/h (BRS = 0.76); 25° seatback, 32 km/h (BRS = 0.89); and 45° seatback, 32 km/h (BRS = 0.93). In the fourth test condition, 45° seatback, 15 km/h, the dummy demonstrated good biofidelity with a BRS score of 1.06. The dummy demonstrated good durability. No damage was identified with a full inspection conducted after the tests.


Assuntos
Acidentes de Trânsito , Manequins , Humanos , Fenômenos Biomecânicos , Aceleração , Desenho de Equipamento , Cadáver , Automóveis , Masculino
8.
Life (Basel) ; 13(3)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36983956

RESUMO

(1) Background: A well-established Boron Neutron Capture Therapy (BNCT) facility includes many essential systems, which are the epithermal neutron beam system, on-line monitoring system (OMS), QA/QC (quality assurance or quality control) system, boron concentration (BC) measurement system, and treatment planning system (TPS). Accurate data transmission, monitoring, and deposition among these systems are of vital importance before, during, and after clinical, animal, and cell BNCT irradiation. This work developed a novel integrated platform NeuTHOR Station (NeuTHORS) for BNCT at Tsing Hua Open-pool Reactor (THOR). Apart from the data of the OMS and QA/QC system, the data of BC and TPS can be loaded on NeuTHORS before BNCT clinical, animal, and cell irradiation. (2) Methods: A multi-paradigm computer programming language c# (c sharp) was used to develop the integrated platform NeuTHORS. The design of NeuTHORS is based on the standard procedures of BNCT treatment or experiment at THOR. Moreover, parallel testing with OMS-BNCT (the former OMS) and QA/QC of THOR was also performed for more than 70 times to verify the validation of NeuTHORS. (3) Results: According to the comparisons of the output, NeuTHORS and OMS-BNCT and QA/QC of THOR show very good consistency. NeuTHORS is now installed on an industrial PC (IPC) and successfully performs the monitoring of BNCT Treatment at THOR. Patients' f BC and TPS data are also input into NeuTHORS and stored on IPC through an internal network from BC measurement room and TPS physicist. Therefore, the treatment data of each patient can be instantaneously established after each BNCT treatment for further study on BNCT. NeuTHORS can also be applied on data acquisition for a BNCT-related study, especially for animal or cell irradiation experiments. (4) Conclusions: A novel integrated platform NeuTHOR Station for monitoring BNCT clinical treatment and animal and cell irradiation study has been successfully established at THOR. With this platform, BNCT radiobiology investigations will be efficiently performed and a thorough data storage and analysis system of BNCT treatments or experiments can thus be systematically built up for the further investigation of BNCT at THOR.

9.
Traffic Inj Prev ; 24(1): 56-61, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36374230

RESUMO

OBJECTIVE: The aim of this study was to assess head injury criteria based on their correlation to brain strain in a Finite Element (FE) head model (the KTH Royal Institute of Technology model), by simulation of head kinematics data from frontal and side crash tests with Anthropomorphic Test Devices (ATDs), and from Human Body Model (HBM) accident reconstructions. METHODS: Six Degrees of Freedom (DoF) head kinematic data was extracted from 221 crash tests, consisting of frontal impacts with the THOR-50M ATD, near-side and far-side impacts with the WorldSID-50M ATD, and from 19 FE HBM accident reconstructions. The head injury criteria HIC15, HIP, BrIC, UBrIC, DAMAGE and CIBIC were calculated, and FE head model simulations were conducted using the six DoF kinematics data. The 100th, 99th, and 95th percentile Maximum Principal Strains (MPS) of the brain were extracted and linear regression models with respect to the injury criteria were created. The injury criteria were then evaluated based on the coefficient of determination, R2, and the Normalized Root Mean Square Error (NRMSE) of each regression model. RESULTS: For all the data sets combined and for the WorldSID far-side data, CIBIC had the best goodness of fit, with R2 of 0.76 and 0.85. For frontal impacts with THOR and the combined ATD data set, DAMAGE had highest R2, 0.83 and 0.78, respectively. Injury criteria including translational accelerations were ranked lower, and BrIC were among the three lowest ranked for most data sets evaluated. UBrIC generally ranked after DAMAGE and CIBIC with respect to the goodness of fit but had the lowest NRMSE for all data sets. CONCLUSIONS: The two mass-spring-damper brain surrogate model criteria, DAMAGE and CIBIC, were best in capturing the head model MPS response for both the THOR and WorldSID data sets. BrIC had lower correlation to the head model MPS and performed marginally better than the linear acceleration only criteria for all the data sets combined. This study supports the suitability of DAMAGE and CIBIC as brain injury criteria to be used with THOR-50M and WorldSID-50M in vehicle crash test conditions, as they outperform BrIC.


Assuntos
Lesões Encefálicas , Traumatismos Craniocerebrais , Humanos , Acidentes de Trânsito , Fenômenos Biomecânicos , Cabeça/fisiologia
10.
Accid Anal Prev ; 191: 107185, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37429156

RESUMO

The THOR 5th percentile female dummy (THOR-05F) was evaluated for two seating postures/positions in frontal impacts using a generic automotive seat environment. The conditions included 2 crash pulses: a 15 km/h test that utilized 4.5 g acceleration and a 3-point restraint with 2 kN load limiter, and a 32 km/h test that utilized 9.5 g acceleration and a 3-point restraint with a 4.5 kN load limiter and pretensioner, and two seatback angles: 25°, a nominal upright posture, and 45°, a moderate reclined posture. The BRS scores were calculated using the NHTSA BioRank method. Overall biofidelity rating was consider excellent for both seating postures. This evaluation provides an understanding of the THOR-05F response and biofidelity evaluation of the ATD in two seating postures (nominal and reclined). This is essential in the assessment and development of safety measures in emerging ADS-equipped vehicles.


Assuntos
Acidentes de Trânsito , Postura , Humanos , Feminino , Acidentes de Trânsito/prevenção & controle , Fenômenos Biomecânicos , Aceleração , Postura Sentada
11.
Traffic Inj Prev ; 24(sup1): S16-S22, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37267003

RESUMO

OBJECTIVE: The objective of this study was the quantitative evaluation and comparison of the responses of the Hybrid III 5th percentile female (HIII-05F) and the 5th percentile female Test Device for Human Occupant Restraint (THOR-05F) anthropomorphic test devices (ATDs) subjected to abdominal loading conditions. METHOD: The HIII-05F and THOR-05F were subjected to 3 different abdominal loading conditions: fixed-back belt pull (low compression), fixed-back belt pull (high compression), and free-back rigid bar impact at 6 m/s. The stroke of the impact was controlled to represent injurious and noninjurious loading conditions as observed in the experiments with postmortem human subjects (PMHS). Quantitative comparisons were made between the ATD abdominal force and compression responses and biofidelity corridors obtained from matched-pair PMHS tests under identical loading conditions, using the most recent version of the NHTSA Biofidelity Ranking System (BRS). RESULTS: The overall THOR-05F BRS scores across all tests (BRS score = 1.84) indicated good biofidelity. For the belt loading test conditions, the average BRS scores for both THOR-05F (BRS scores = 1.45 and 1.34) and HIII-05F (BRS scores = 1.42 and 1.01) showed good biofidelity. For the rigid bar loading condition, the THOR-05F (BRS score = 2.74) showed better biofidelity compared to HIII-05F (BRS score = 10.63), with the HIII-05F exhibiting poor performance in this condition. The average pressures recorded by the abdomen pressure twin sensors (APTS) in the current study ranged from 45 to 130 kPa, increasing proportionally with higher stroke and loading rate. CONCLUSIONS: Overall, the THOR-05F BRS scores were better than the HIII-05F BRS scores, which suggests improved biofidelity of the THOR-05F abdomen. The abdominal insert in the HIII-05F did not provide enough room for compression, leading to higher stiffness and occupant motion as observed in the rigid bar tests. Because of practical challenges in measuring abdomen deflection in a soft ATD abdomen component, use of APTS in THOR-05F provides the ability to measure the restraint loading to the abdomen and assess the risk of abdominal injury. With good BRS scores observed in this study for THOR-05F, pressure and other measurements included in the THOR-05F may be used to develop abdominal injury risk functions in the future.


Assuntos
Traumatismos Abdominais , Acidentes de Trânsito , Humanos , Feminino , Cadáver , Abdome/fisiologia , Restrição Física , Fenômenos Biomecânicos , Manequins
12.
Traffic Inj Prev ; 24(3): 208-212, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36943173

RESUMO

OBJECTIVE: This study presents a comparison of the Test Device for Human Occupant Restraint (THOR) 50M and Hybrid III (HIII) 50M anthropomorphic test device (ATD) geometries and rear impact head and neck biofidelity to each other and to postmortem human surrogate (PMHS) data to evaluate the usefulness of the THOR in rear impact testing. METHODS: Both ATDs were scanned in a seated position on a rigid bench seat. A series of rear impact sled tests with the rigid bench seat with no head restraint support were conducted with a HIII-50M at 16 and 24 kph. Tests at each speed were performed twice with the THOR-50M to allow an assessment of the repeatability of the THOR-50M. A comparison of the test results from THOR-50M testing were made to the results of a previous study that included PMHS. Rear impact sled tests with both ATDs in a modern seat were then conducted at 40 kph. RESULTS: The THOR-50M head was 48.4 mm rearward and 60.1 mm higher than the HIII-50M head when seated in the rigid bench seat. In the repeated rigid bench testing at 16 and 24 kph, the THOR-50M head longitudinal and vertical accelerations, upper neck moment, and overall kinematics showed good test-to-test repeatability. In the rigid bench tests, the THOR-50M neck experienced flexion prior to extension in the 16 kph tests, where the neck of the HIII only experienced extension. At 24 kph both ATDs only experienced extension. The THOR-50M head displaced more rearward at both test velocities. The rigid bench tests show that the THOR-50M neck allows for more extension motion or articulation than the HIII-50M neck. The rigid bench test also shows that the head longitudinal and vertical accelerations, angular head kinematics, and upper neck moments were reasonably comparable between the ATDs. The THOR-50M results were closer to the average of the PMHS results than the HIII-50-M results, with the exception of the upper neck. In the 40 kph tests, with a modern seat design, the THOR-50M resulted in more deformation of the seatback with greater head restraint loading than the HIII-50M. The THOR-50M head backset distance was less. CONCLUSION: This study provides insight into the differences and similarities between the THOR and the HIII-50M ATD geometries, instrumentation responses, and kinematics, as well as the repeatability of the THOR-50M in rear impacts testing. The overall geometries of the THOR-50M and the HIII-50M are similar. The seated head position of the THOR-50M is slightly further rearward and higher than the HIII-50M. The results indicate that the THOR-50M matches the PMHS results more closely than the HIII-50M and may have improved neck biofidelity in rear impact testing. The results indicate that the studied THOR-50M responses are repeatable within expected test-to-test variations in rear impacts. Early data suggest that the THOR-50M can be used in rear impact testing, though a more complete understanding of the THOR-50M differences to the HIII ATDs will allow for better correlation to the existing body of HIII rear impact testing.


Assuntos
Acidentes de Trânsito , Restrição Física , Humanos , Cadáver , Cabeça/fisiologia , Aceleração , Fenômenos Biomecânicos , Manequins
13.
Cancers (Basel) ; 14(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36139544

RESUMO

BACKGROUND: Although DNA methylation in the gene promoters usually represses gene expression, the TERT hypermethylated oncological region (THOR) located 5' of the hTERT gene is hypermethylated when hTERT is expressed in diverse cancer types, including urothelial cancer (UC). METHODS: Comprehensive MeDIP and DNA methylation array analyses complemented by the technically independent method of bisulfite genomic sequencing were applied on pathologically reviewed and classified urothelial carcinoma specimens and healthy urothelial tissue samples to reveal the methylation status of THOR in detail. RESULTS: The detailed DNA methylation profiles reveal the exact positions of differentially methylated CpG dinucleotides within THOR in urothelial cancer and provide evidence ofa diverging role of methylation of these CpGs in the regulation of hTERT. In particular, our data suggest a regulating mechanism in which THOR methylation acts on hTERT expression through epigenetic silencing of the lncRNA hTERT antisense promoter-associated (hTAPAS), which represses hTERT. CONCLUSIONS: These findings precisely define the most differentially methylated CpGs of THOR in early urothelial cancer, enabling optimal design of Methylation-Specific PCR (MSPCR) primers to reliably probe these methylation differences for diagnostic and prognostic purposes. In addition, this strategy presents a prime example that is also applicable to many other malignancies. Finally, the first evidence for the underlying epigenetic mechanism regulating hTERT expression through the methylation status of THOR is provided.

14.
Clin Epigenetics ; 14(1): 178, 2022 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-36529814

RESUMO

BACKGROUND: Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of death among women worldwide. Early BC is potentially curable, but the mortality rates still observed among BC patients demonstrate the urgent need of novel and more effective diagnostic and therapeutic options. Limitless self-renewal is a hallmark of cancer, governed by telomere maintenance. In around 95% of BC cases, this process is achieved by telomerase reactivation through upregulation of the human telomerase reverse transcriptase (hTERT). The hypermethylation of a specific region within the hTERT promoter, termed TERT hypermethylated oncological region (THOR) has been associated with increased hTERT expression in cancer. However, its biological role and clinical potential in BC have never been studied to the best of our knowledge. Therefore, we aimed to investigate the role of THOR as a biomarker and explore the functional impact of THOR methylation status in hTERT upregulation in BC. RESULTS: THOR methylation status in BC was assessed by pyrosequencing on discovery and validation cohorts. We found that THOR is significantly hypermethylated in malignant breast tissue when compared to benign tissue (40.23% vs. 12.81%, P < 0.0001), differentiating malignant tumor from normal tissue from the earliest stage of disease. Using a reporter assay, the addition of unmethylated THOR significantly reduced luciferase activity by an average 1.8-fold when compared to the hTERT core promoter alone (P < 0.01). To further investigate its biological impact on hTERT transcription, targeted THOR demethylation was performed using novel technology based on CRISPR-dCas9 system and significant THOR demethylation was achieved. Cells previously demethylated on THOR region did not develop a histologic cancer phenotype in in vivo assays. Additional studies are required to validate these observations and to unravel the causality between THOR hypermethylation and hTERT upregulation in BC. CONCLUSIONS: THOR hypermethylation is an important epigenetic mark in breast tumorigenesis, representing a promising biomarker and therapeutic target in BC. We revealed that THOR acts as a repressive regulatory element of hTERT and that its hypermethylation is a relevant mechanism for hTERT upregulation in BC.


Assuntos
Neoplasias da Mama , Telomerase , Humanos , Feminino , Telomerase/genética , Telomerase/metabolismo , Metilação de DNA , Neoplasias da Mama/genética , Epigênese Genética , Biomarcadores/metabolismo
15.
Med Oncol ; 39(12): 207, 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175594

RESUMO

The long noncoding RNA (lncRNA) THOR is highly conserved and expressed in various human cancer tissues, although its potential role and underlying mechanism in endometrial cancer (EC) remain unknown. This study aims to explore THOR's biological function and molecular mechanism in EC progression. THOR expression in EC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR) and in situ hybridization (ISH). THOR expression based on The Cancer Genome Atlas (TCGA) and clinical sample analyses was significantly higher in EC tissues than normal tissues, and higher THOR levels were closely associated with poor overall survival in EC. Additionally, a positive correlation between ISH-detected THOR expression and pathological grade was observed. CCK-8, colony formation, and transwell migration and invasion assays revealed that THOR significantly enhances the proliferation, migration, and invasion abilities of EC cells. Moreover, IGF2BP1 protein expression and ERK and AKT protein phosphorylation levels in EC cells increased significantly with THOR overexpression in EC cells. In conclusion, our findings suggest that THOR promotes EC cell growth and invasion, and IGF2BP1-mediated AKT and ERK signaling pathways activation might be involved. Clinically, THOR is significantly expressed in EC, and high THOR expression correlates with poor prognosis, making it a potential prognostic marker for EC.


Assuntos
Neoplasias do Endométrio , RNA Longo não Codificante , Neoplasias do Endométrio/genética , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Sincalida
16.
Healthcare (Basel) ; 10(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36360488

RESUMO

The healthcare environment presents a large volume of personal and sensitive patient data that needs to be available and secure. Information and communication technology brings a new reality to healthcare, promoting improvements, agility and integration. Regarding high-level and complex decision-making scenarios, the Brazilian Navy (BN), concerning its healthcare field, is seeking to provide better management of its respective processes in its hospital facilities, allowing accurate control of preventive and curative medicine to members who work or have served there in past years. The study addresses the understanding, structure and clarifying variables related to the feasibility of technological updating and installing of a Hospital Information System (HIS) for BN. In this scenario, through interviews and analysis of military organization business processes, criteria and alternatives were established based on multi-criteria methodology as a decision aid. As methodological support for research and data processing, THOR 2 and PROMETHEE-SAPEVO-M1 methods were approached, both based on the scenarios of outranking alternatives based on the preferences established by the stakeholders in the problem. As a result of the methodological implementation, we compare the two implemented methods in this context, exposing the Commercial Software Purchase and Adoption of Free Software, integrated into Customization by the Marine Studies Foundation, as favorable actions to be adopted concerning HIS feasibility. This finding generates a comprehensive discussion regarding the BN perspective and changes in internal development in the military environment, prospecting alignment to the culture of private organizations in Information Technology for healthcare management. In the end, we present some conclusions concerning the study, exploring the main points of the decision-making analysis and for future research.

17.
Stapp Car Crash J ; 66: 143-173, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37733824

RESUMO

In order to evaluate the THOR-50M as a front impact Anthropomorphic Test Device (ATD) for vehicle safety design, the ATD was compared to the H3-50M in matching vehicle crash tests for 20 unique vehicle models from 2 vehicle manufacturers. For the belted driver condition, a total of fifty-four crash tests were investigated in the 56.3 km/h (35 mph) front rigid barrier impact condition. Four more tests were compared for the unbelted driver and right front passenger at 40.2 km/h (25 mph) in the flat frontal and 30-degree right oblique rigid barrier impact conditions. The two ATDs were also evaluated for their ability to predict injury risk by comparing their fleet average injury risk to Crash Investigation Sampling System (CISS) accident data for similar conditions. The differences in seating position and their effect on ATD responses were also investigated. This study showed that the belted THOR-50M injury responses were higher than the H3-50M by 25%-180%, in all reported ATD responses, except chest acceleration. For one unbelted condition, the THOR-50M reported 200%-300% higher neck responses than the H3-50M, primarily due to head contact to the roof structure in a mid-sized sedan. The THOR-50M overpredicted the injury risk based on chest deflection compared to the CISS accident data by at least a factor of 4 times. The THOR-50M also overpredicted the injury risk based on BrIC by at least a factor of 10 times. Future work is needed to investigate these overpredictions with respect to ATD construction, injury risk curves, and seating procedures.


Assuntos
Aceleração , Automóveis , Manequins , Humanos , Masculino , Acidentes de Trânsito
18.
JTCVS Open ; 11: 265-271, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35664693

RESUMO

Objectives: The coronavirus disease 2019 (COVID-19) pandemic negatively impacted cardiothoracic (CT) surgery, with changes in clinical, academic, and personal responsibilities. We hypothesized that the pandemic may disproportionately impact female academic CT surgeons, accentuating preexisting sex disparities. This study assessed sex differences in authorship of 2 major CT surgery journals during the early part of the COVID-19 pandemic. Methods: All accepted submissions to The Annals of Thoracic Surgery and The Journal of Thoracic and Cardiovascular Surgery between April and August of 2019 and the same period in 2020 were reviewed. Article type and author characteristics were obtained from the journals. Author sex was predicted using a validated multinational database (Genderize.io) and verified with authors' institutional and public professional profiles. Results: In total, 1106 submissions were accepted during the 2019 period, whereas 900 articles (18.6% decrease) were accepted during the same period in 2020. Original research articles comprised 33.3% of the 2019 articles but only 4.9% of the 2020 articles. Female authors contributed to 39.3% (23.1% original research and 16.2% nonoriginal articles) and 29.4% (3.3% original research and 26.1% nonoriginal articles) of articles during the 2019 and 2020 periods, respectively. This represents a marked change in the type of articles that female authors contributed to. Conclusions: Early on during the COVID-19 pandemic, the type of articles accepted, and authorship demographic changed. There was a decrease in contribution of female-authored CT surgery articles submitted to both journals, especially for original research. Future research will elucidate the long-term impact of the pandemic on sex disparities in academic productivity.

19.
Traffic Inj Prev ; 22(sup1): S155-S158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34686084

RESUMO

OBJECTIVE: Anthropomorphic test devices (ATD) are used in crashworthiness studies to advance safety in automotive, military, aviation, and other environments. The Test Device for Human Occupant Restraint (THOR) is an advancement over the widely used Hybrid III ATD. The female version THOR-05F is different from the male as it is not a scaled-down version of the male, and it is based on the recognition that the cervical spines (necks) of females have a different response than males. The objective of this study is to evaluate its response at dynamic rates of loading and compare it with previous postmortem human surrogate (PMHS) responses under sagittal plane bending. METHODS: The head/neck assembly was separated from the thorax, and a lower neck plate was attached to the head/neck assembly to mount the preparation to the frame of an electro-hydraulic testing device. A custom upper neck interface plate was attached to a novel angular displacement test device that converted the linear motion of the vertical electrohydraulic piston to moment loading at the occipital condyle joint. The neck was preconditioned by applying a sinusoidal 10-degree flexion-extension cycle for 90 s and then three repeat dynamic tests at a target rate of 90 Nm/s. Flexion and extension tests were performed with and without the front and rear neck cables of the THOR-05F neck. Targets were fixed to the upper neck adapter plate, occipital condyle joint, mid-spine aluminum puck, and lower neck adapter plate. The targets' three-dimensional positions were measured using a seven-camera optical motion capture system. Upper neck load cell and occipital condyle potentiometer data were sampled at 20 kHz, and loading rates were determined by calculating the sagittal moment slope between 15% and 85% of the signal. RESULTS: The mean occipital condyle angle versus sagittal moment response from the 12 tests (three tests each with and without cables and under flexion and extension) are given in the body of the manuscript. With and without cables, the loading rates for flexion tests were 89.3 ± 0.5 Nm/s and 86.3 ± 0.4 Nm/s, and for extension tests they were 90.8 ± 1.2 Nm/s and 88.0 ± 1.5 Nm/s. The average peak sagittal moments were 34.2 ± 0.3 Nm and 30.3 ± 0.2 Nm for flexion and 50.6 ± 0.3 Nm and 47.0 ± 0.3 Nm for extension tests. The mean peak occipital condyle angles were 23.5 ± 0.2 deg and 25.3 ± 0.1 deg for flexion and 22.7 ± 0.2 deg and 25.8 ± 0.1 deg for extension. CONCLUSION: Using the angular motion as a basis and comparing it with the previously conducted PMHS tests, the THOR-05F neck has approximately twice the stiffness of the human under sagittal plane bending.


Assuntos
Acidentes de Trânsito , Pescoço , Fenômenos Biomecânicos , Cadáver , Feminino , Cabeça/fisiologia , Humanos , Masculino , Pescoço/fisiologia
20.
Front Microbiol ; 12: 672910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093493

RESUMO

Microbial communities are essential for human and environmental health, often forming complex interaction networks responsible for driving ecosystem processes affecting their local environment and their hosts. Disturbances of these communities can lead to loss of interactions and thereby important ecosystem functionality. The research on what drives interactions in microbial communities is still in its infancy, and much information has been gained from the study of model communities. One purpose of using these model microbial communities is that they can be cultured under controlled conditions. Yet, it is not well known how fluctuations of abiotic factors such as temperature affect their interaction networks. In this work, we have studied the effect of temperature on interactions between the members of the model community THOR, which consists of three bacterial species: Pseudomonas koreensis, Flavobacterium johnsoniae, and Bacillus cereus. Our results show that the community-intrinsic properties resulting from their interspecies interactions are highly dependent on incubation temperature. We also found that THOR biofilms had remarkably different abundances of their members when grown at 11, 18, and 25°C. The results suggest that the sensitivity of community interactions to changes in temperature is influenced, but not completely dictated, by different growth rates of the individual members at different temperatures. Our findings likely extend to other microbial communities and environmental parameters. Thus, temperature could affect community stability and may influence diverse processes including soil productivity, bioprocessing, and disease suppression. Moreover, to establish reproducibility between laboratories working with microbial model communities, it is crucial to ensure experimental stability, including carefully managed temperature conditions.

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