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This case study describes a fatal head injury in a 1-year-old child involved in a motor vehicle accident in Japan. The child, secured in a rear-facing child seat, was a passenger in a car driven by their mother when the offset car-to-car collision occurred. The car rotated counterclockwise before coming to a stop. Despite remaining secured in the child seat, the child suffered severe head trauma, leading to cardiac arrest. Autopsy computed tomography revealed a right open depressed fracture, left head contusion, traumatic subarachnoid hemorrhage, intraventricular hemorrhage, and pneumocephalus. The injury mechanism involved the child's head striking the right headrest, followed by a swing to the left, induced by the initial impact and subsequent rotational movement. This case highlights the importance of age-specific data in understanding pediatric injuries in motor vehicle accidents and improving child seat safety measures.
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Accidentes de Tránsito , Sistemas de Retención Infantil , Humanos , Lactante , Resultado Fatal , Tomografía Computarizada por Rayos X , Masculino , Traumatismos Craneocerebrales , Paro Cardíaco/etiología , Japón , Fractura Craneal Deprimida/diagnóstico por imagen , Hemorragia Subaracnoidea Traumática/diagnóstico por imagen , Hemorragia Subaracnoidea Traumática/etiologíaRESUMEN
Liver cancer, specifically hepatocellular carcinoma (HCC), is a major global health concern due to its high prevalence in many countries [...].
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/patología , Prevalencia , Salud GlobalRESUMEN
Oligonucleotide therapeutics, drugs consisting of 10-50 nucleotide-long single- or double-stranded DNA or RNA molecules that can bind to specific DNA or RNA sequences or proteins, include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), aptamers, and decoys. These oligonucleotide therapeutics could potentially become the third pillar of drug development. In particular, ASOs and siRNAs are advanced tools that are widely used to silence gene expression. They are used in clinical trials, as they have high specificity for target mRNAs and non-coding RNAs and limited toxicity. However, their clinical application remains challenging. Although chemotherapy has benefits, it has severe adverse effects in many patients. Therefore, new modalities for targeted molecular therapy against tumors, including oligonucleotide therapeutics, are required, and they should be compatible with diagnosis using next-generation sequencing. This review provides an overview of the therapeutic uses of ASOs, siRNAs, and miRNAs in clinical studies on malignant tumors. Understanding previous research and development will help in developing novel oligonucleotide therapeutics against malignant tumors.
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MicroARNs , Neoplasias , Anticuerpos , Humanos , MicroARNs/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Oligonucleótidos/farmacología , Oligonucleótidos/uso terapéutico , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/farmacología , Oligonucleótidos Antisentido/uso terapéutico , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , ARN Interferente Pequeño/uso terapéuticoRESUMEN
INTRODUCTION: There are limited reports on the natural history of hen's egg (HE) allergy (HEA) in children <6 years. We aimed to investigate the natural history of HEA in children aged 6-12 years and the factors affecting its tolerance acquisition. METHODS: Using the database in our hospital, a total of 137 patients diagnosed with a definitive immediate-type reaction to HE when they turned 6 years were enrolled, and the natural course of HEA was prospectively examined until patients turned 12 years. Tolerance was defined as being able to pass an oral food challenge to consume a half or whole heated HE or consume heated HE freely without symptoms. Thirty patients (21.9%) who were enrolled for oral immunotherapy and 21 (15.3%) who discontinued follow-up were considered dropouts. Kaplan-Meier estimation was used to evaluate the rate of tolerance. RESULTS: Fifty-five of the 137 patients (40.1%) had a previous HE anaphylaxis history; 61 (44.5%) patients had acquired tolerance to HE by age 12 years; and 25 (18.2%) continued total or partial HE elimination. The estimated acquired tolerance rates by ages 7, 9, and 12 years were 14.6%, 40.8%, and 60.5%, respectively. A previous history of HE anaphylaxis before 6 years of age, reacting to small amounts of heated HE by 6 years of age, and higher ovomucoid-specific immunoglobulin E values at the same age were associated with persistent HEA. CONCLUSION: This study provides important insights into the natural course of HEA beyond early childhood, with the acquisition of HE tolerance continuing throughout the duration of the study.
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Alérgenos/inmunología , Hipersensibilidad al Huevo/epidemiología , Hipersensibilidad al Huevo/etiología , Huevos/efectos adversos , Biomarcadores , Niño , Hipersensibilidad al Huevo/diagnóstico , Hipersensibilidad al Huevo/terapia , Femenino , Humanos , Tolerancia Inmunológica , Inmunización , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Estimación de Kaplan-Meier , Masculino , Anamnesis , Evaluación del Resultado de la Atención al Paciente , Pronóstico , Estudios Prospectivos , Vigilancia en Salud PúblicaRESUMEN
PRDI-BF1 and RIZ (PR) domain zinc finger protein 14 (PRDM14), first reported in 2007 to be overexpressed in breast cancer, plays an important role in breast cancer proliferation. Subsequent studies reported that PRDM14 is expressed in embryonic stem cells, primordial germ cells, and various cancers. PRDM14 was reported to confer stemness properties to cancer cells. These properties induce cancer initiation, cancer progression, therapeutic resistance, distant metastasis, and recurrence in refractory tumors. Therefore, PRDM14 may be an ideal therapeutic target for various types of tumors. Silencing PRDM14 expression using PRDM14-specific siRNA delivered through an innovative intravenous drug delivery system reduced the size of inoculated tumors, incidence of distant metastases, and increased overall survival in nude mice without causing adverse effects. Therapeutic siRNA targeting PRDM14 is now being evaluated in a human phase I clinical trial for patients with refractory breast cancer, including triple-negative breast cancer.
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Neoplasias de la Mama , Proteínas de Unión al ADN , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Proteínas de Unión al ADN/metabolismo , Femenino , Humanos , Ratones , Ratones Desnudos , ARN Interferente Pequeño , Proteínas de Unión al ARN/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Dedos de ZincRESUMEN
The accumulation of mutations in cancer driver genes, such as tumor suppressors or proto-oncogenes, affects cellular homeostasis. Disturbances in the mechanism controlling proliferation cause significant augmentation of cell growth and division due to the loss of sensitivity to the regulatory signals. Nowadays, an increasing number of cases of liver cancer are observed worldwide. Data provided by the International Cancer Genome Consortium (ICGC) have indicated many alterations within gene sequences, whose roles in tumor development are not well understood. A comprehensive analysis of liver cancer (virus-associated hepatocellular carcinoma) samples has identified new and rare mutations in B-Raf proto-oncogene (BRAF) in Japanese HCC patients, as well as BRAF V600E mutations in French HCC patients. However, their function in liver cancer has never been investigated. Here, using functional analysis and next generation sequencing, we demonstrate the tumorigenic effect of BRAF V600E on hepatocytes (THLE-2 cell line). Moreover, we identified genes such as BMP6, CXCL11, IL1B, TBX21, RSAD2, MMP10, and SERPIND1, which are possibly regulated by the BRAF V600E-mediated, mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) signaling pathway. Through several functional assays, we demonstrate that BRAF L537M, D594A, and E648G mutations alone are not pathogenic in liver cancer. The investigation of genome mutations and the determination of their impact on cellular processes and functions is crucial to unraveling the molecular mechanisms of liver cancer development.
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Carcinoma Hepatocelular/genética , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Neoplasias Hepáticas/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Hígado/química , Fenotipo , RNA-Seq , Transducción de SeñalRESUMEN
PRDM14 is highly expressed in several cancers but is not detected in normal tissues. It confers cancer stem cell-like properties, including chemoresistance and distant metastasis, to cancer cells. Herein, we aimed to develop a highly effective therapy against advanced stage cancer based on intravenously delivered PRDM14-targeted siRNA. First, we examined PRDM14 expression and gene amplification in breast and pancreatic tumors and cell lines. PRDM14 was expressed in breast cancer, including the triple-negative subtype, and pancreatic cancer. PRDM14 was amplified in 23.8% of patients with PRDM14+ breast cancer. Next, we investigated the inoculated tumor growth and distant metastasis following PRDM14 depletion by administering mice with PRDM14-specific chimeric siRNA combined with a novel branched PEGylated poly-L-ornithine (PLO)-based intravenous drug delivery system, designated PRDM14 unit polyion complex (uPIC) (n = 6/group). Inhibition of PRDM14 expression with PRDM14 uPIC by systemic intravenous injection effectively reduced tumor size and metastasis in vivo, thereby improving survival. Finally, pharmacokinetic/toxicokinetic analyses were performed on PRDM14 uPIC, which was intravenously administered to rats (n = 10-15/group) and cynomolgus monkeys (n = 3-5/group), twice weekly for 4 weeks. This revealed that PRDM14 uPIC was relatively nontoxic and the siRNA exposure in serum was greater than that predicted by the administered dose ratio when delivered as a uPIC. Taken together, our study indicated that PRDM14 uPIC is highly effective in suppressing malignant features of solid cancers and does not cause severe toxicity, making it a promising therapeutic agent for cancer treatment.
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Neoplasias de la Mama/terapia , Proteínas de Unión al ADN/antagonistas & inhibidores , Sistemas de Liberación de Medicamentos , Neoplasias Pulmonares/terapia , Nanopartículas/administración & dosificación , Neoplasias Pancreáticas/terapia , ARN Interferente Pequeño/genética , Proteínas de Unión al ARN/antagonistas & inhibidores , Factores de Transcripción/antagonistas & inhibidores , Animales , Apoptosis , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proliferación Celular , Proteínas de Unión al ADN/genética , Femenino , Haplorrinos , Humanos , Inyecciones Intravenosas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Ratones , Nanopartículas/química , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Pronóstico , Proteínas de Unión al ARN/genética , Ratas , Factores de Transcripción/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of Humulus lupulus L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, antiviral, antifungal, antigenotoxic, antiangiogenic, and antimalarial effects as well as strong anticancer activity towards various types of cancer cells. XH acts as a wide ranging chemopreventive and anticancer agent, and its isomer, 8-prenylnaringenin, is a phytoestrogen with strong estrogenic activity. The present review focuses on the bioactivity of XH on various types of cancers and its pharmacokinetics. In this paper, we first highlight, in brief, the history and use of hops and then the chemistry and structure-activity relationship of XH. Lastly, we focus on its prominent effects and mechanisms of action on various cancers and its possible use in cancer prevention and treatment. Considering the limited number of available reviews on this subject, our goal is to provide a complete and detailed understanding of the anticancer effects of XH against different cancers.
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Antineoplásicos Fitogénicos/farmacocinética , Flavonoides/química , Flavonoides/farmacocinética , Humulus , Neoplasias/tratamiento farmacológico , Propiofenonas/química , Propiofenonas/farmacocinética , Animales , Antineoplásicos Fitogénicos/química , Femenino , Humanos , Humulus/química , Humulus/crecimiento & desarrollo , Masculino , Neoplasias/patologíaRESUMEN
Geographically, East Asia had the highest liver cancer burden in 2017. Besides this, liver cancer-related deaths were high in Japan, accounting for 3.90% of total deaths. The development of liver cancer is influenced by several factors, and genetic alteration is one of the critical factors among them. Therefore, the detailed mechanism driving the oncogenic transformation of liver cells needs to be elucidated. Recently, many researchers have focused on investigating the liver cancer genome and identified somatic mutations (MTs) of several transcription factors. In this line, next-generation sequencing of the cancer genome identified that oxidative stress-related transcription factor NRF2 (NFE2L2) is mutated in different cancers, including hepatocellular carcinoma (HCC). Here, we demonstrated that NRF2 DLG motif mutations (NRF2 D29A and L30F), found in Japanese liver cancer patients, upregulate the transcriptional activity of NRF2 in HCC cell lines. Moreover, the transcriptional activity of NRF2 mutations is not suppressed by KEAP1, presumably because NRF2 MTs disturb proper NRF2-KEAP1 binding and block KEAP1-mediated degradation of NRF2. Additionally, we showed that both MTs upregulate the transcriptional activity of NRF2 on the MMP9 promoter in Hepa1-6 and Huh7 cells, suggesting that MT derived gain-of-function of NRF2 may be important for liver tumor progression. We also found that ectopic overexpression of oncogenic BRAF WT and V600E increases the transcriptional activity of NRF2 WT on both the 3xARE reporter and MMP9 promoter. Interestingly, NRF2 D29A and L30F MTs with oncogenic BRAF V600E MT synergistically upregulate the transcription activity of NRF2 on the 3xARE reporter and MMP9 promoter in Hepa1-6 and Huh7 cells. In summary, our findings suggest that MTs in NRF2 have pathogenic effects, and that NRF2 MTs together with oncogenic BRAF V600E MT synergistically cause more aberrant transcriptional activity. The high activity of NRF2 MTs in HCC with BRAF MT warrants further exploration of the potential diagnostic, prognostic, and therapeutic utility of this pathway in HCC.
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Carcinoma Hepatocelular/genética , Factor 2 Relacionado con NF-E2/genética , Secuencias de Aminoácidos/genética , Carcinogénesis/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Japón , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Mutación , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/genética , Pronóstico , Regiones Promotoras Genéticas/genética , Transducción de Señal/genéticaRESUMEN
The molecular mechanism underlying embryonic implantation is vital to understand the correct communications between endometrium and developing conceptus during early stages of pregnancy. This study's objective was to determine molecular changes in the uterine endometrial proteome during the preimplantation and peri-implantation between 9 days (9D), 12 days (12D), and 16 days (16D) of pregnant Polish Large White (PLW) gilts. 2DE-MALDI-TOF/TOF and ClueGOTM approaches were employed to analyse the biological networks and molecular changes in porcine endometrial proteome during maternal recognition of pregnancy. A total of sixteen differentially expressed proteins (DEPs) were identified using 2-DE gels and MALDI-TOF/TOF mass spectrometry. Comparison between 9D and 12D of pregnancy identified APOA1, CAPZB, LDHB, CCT5, ANXA4, CFB, TTR upregulated DEPs, and ANXA5, SMS downregulated DEPs. Comparison between 9D and 16D of pregnancy identified HP, APOA1, ACTB, CCT5, ANXA4, CFB upregulated DEPs and ANXA5, SMS, LDHB, ACTR3, HP, ENO3, OAT downregulated DEPs. However, a comparison between 12D and 16D of pregnancy identified HP, ACTB upregulated DEPs, and CRYM, ANXA4, ANXA5, CAPZB, LDHB, ACTR3, CCT5, ENO3, OAT, TTR down-regulated DEPs. Outcomes of this study revealed key proteins and their interactions with metabolic pathways involved in the recognition and establishment of early pregnancy in PLW gilts.
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Implantación del Embrión/fisiología , Endometrio/metabolismo , Preñez/metabolismo , Proteínas/metabolismo , Animales , Femenino , Embarazo , Proteínas/análisis , Reproducibilidad de los Resultados , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , PorcinosRESUMEN
Ionizing radiation is a risk factor for myeloid neoplasms including myelodysplastic syndromes (MDS), and atomic bomb survivors have been shown to have a significantly higher risk of MDS. Our previous analyses demonstrated that MDS among these survivors had a significantly higher frequency of complex karyotypes and structural alterations of chromosomes 3, 8, and 11. However, there was no difference in the median survival time between MDS among survivors compared with those of de novo origin. This suggested that a different pathophysiology may underlie the causative genetic aberrations for those among survivors. In this study, we performed genome analyses of MDS among survivors and found that proximally exposed patients had significantly fewer mutations in genes such as TET2 along the DNA methylation pathways, and they had a significantly higher rate of 11q deletions. Among the genes located in the deleted portion of chromosome 11, alterations of ATM were significantly more frequent in proximally exposed group with mutations identified on the remaining allele in 2 out of 5 cases. TP53, which is frequently mutated in therapy-related myeloid neoplasms, was equally affected between proximally and distally exposed patients. These results suggested that the genetic aberration profiles in MDS among atomic bomb survivors differed from those in therapy-related and de novo origin. Considering the role of ATM in DNA damage response after radiation exposure, further studies are warranted to elucidate how 11q deletion and aberrations of ATM contribute to the pathogenesis of MDS after radiation exposure.
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Supervivientes a la Bomba Atómica , Síndromes Mielodisplásicos , Aberraciones Cromosómicas , Humanos , Síndromes Mielodisplásicos/etiología , Síndromes Mielodisplásicos/genética , Factores de Riesgo , SobrevivientesRESUMEN
Coronavirus disease 2019 (COVID-19) is spreading worldwide and poses an imminent threat to public health. We encountered 2 cases of COVID-19 with progression resulting in severe respiratory failure and improvement without any specific treatment. To examine the course of infection, we performed reverse-transcription (RT) polymerase chain reaction assay with serum specimens, and serum SARS-CoV-2 RNA was detected in both cases when body temperature increased and respiratory status deteriorated. We, then examined, retrospectively and prospectively, the clinical course during hospitalization by performing serial examinations of serum SARS-CoV-2 RNA status. The findings from our cases suggest that not only is detection of viremia useful as a predictive marker of severity, but also serial serum SARS-CoV-2 RNA results can be helpful for predicting the clinical course.
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Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , ARN Viral/sangre , Insuficiencia Respiratoria/diagnóstico , Viremia/diagnóstico , Adulto , Anciano , Betacoronavirus/genética , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Humanos , Masculino , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/virología , ARN Viral/aislamiento & purificación , Insuficiencia Respiratoria/sangre , Insuficiencia Respiratoria/virología , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores de Tiempo , Viremia/complicaciones , Viremia/virologíaRESUMEN
PURPOSE: Our previous studies demonstrated that mature adipocyte-derived dedifferentiated fat (DFAT) cells possess similar multipotency as mesenchymal stem cells. Here, we examined the immunoregulatory potential of DFAT cells in vitro and the therapeutic effect of DFAT cell transplantation in a mouse inflammatory bowel disease (IBD) model. METHODS: The effect of DFAT cell co-culture on T cell proliferation and expression of immunosuppression-related genes in DFAT cells were evaluated. To create IBD, CD4+CD45RBhigh T cells were intraperitoneally injected into SCID mice. One week later, DFAT cells (1 × 105, DFAT group) or saline (Control group) were intraperitoneally injected. Subsequently bodyweight was measured every week and IBD clinical and histological scores were evaluated at 5 weeks after T cell administration. RESULTS: The T cell proliferation was inhibited by co-cultured DFAT cells in a cell density-dependent manner. Gene expression of TRAIL, IDO1, and NOS2 in DFAT cells was upregulated by TNFα stimulation. DFAT group improved IBD-associated weight loss, IBD clinical and histological scores compared to Control group. CONCLUSION: DFAT cells possess immunoregulatory potential and the cell transplantation promoted recovery from colon damage and improved clinical symptoms in the IBD model. DFAT cells could play an important role in the treatment of IBD.
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Adipocitos/metabolismo , Adipocitos/trasplante , Desdiferenciación Celular/fisiología , Trasplante de Células/métodos , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/terapia , Animales , Técnicas de Cultivo de Célula , Proliferación Celular , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB CRESUMEN
PRDM (PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) homologous domain-containing) transcription factors are a group of proteins that have a significant impact on organ development. In our study, we assessed the role of Prdm3 in neurogenesis and the mechanisms regulating its expression. We found that Prdm3 mRNA expression was induced during neurogenesis and that Prdm3 gene knockout caused premature neuronal differentiation of the P19 cells and enhanced the growth of non-neuronal cells. Interestingly, we found that Gata6 expression was also significantly upregulated during neurogenesis. We further studied the regulatory mechanism of Prdm3 expression. To determine the role of GATA6 in the regulation of Prdm3 mRNA expression, we used a luciferase-based reporter assay and found that Gata6 overexpression significantly increased the activity of the Prdm3 promoter. Finally, the combination of retinoic acid receptors α and ß, along with Gata6 overexpression, further increased the activity of the luciferase reporter. Taken together, our results suggest that in the P19 cells, PRDM3 contributed to neurogenesis and its expression was stimulated by the synergism between GATA6 and the retinoic acid signaling pathway.
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Diferenciación Celular/genética , Proteína del Locus del Complejo MDS1 y EV11/genética , Neurogénesis/genética , Neuronas/metabolismo , Animales , Eliminación de Gen , Regulación del Desarrollo de la Expresión Génica/genética , Humanos , Ratones , Regiones Promotoras Genéticas , ARN Mensajero/genética , Transducción de Señal , Factores de Transcripción/genética , Tretinoina/metabolismoRESUMEN
NF-E2-related factor 2 (NRF2) is a basic leucine zipper transcription factor, a master regulator of redox homeostasis regulating a variety of genes for antioxidant and detoxification enzymes. NRF2 was, therefore, initially thought to protect the liver from oxidative stress. Recent studies, however, have revealed that mutations in NRF2 cause aberrant accumulation of NRF2 in the nucleus and exert the upregulation of NRF2 target genes. Moreover, among all molecular changes in hepatocellular carcinoma (HCC), NRF2 activation has been revealed as a more prominent pathway contributing to the progression of precancerous lesions to malignancy. Nevertheless, how its activation leads to poor prognosis in HCC patients remains unclear. In this review, we provide an overview of how aberrant activation of NRF2 triggers HCC development. We also summarize the emerging roles of other NRF family members in liver cancer development.
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Carcinogénesis/genética , Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Proteína 1 Asociada A ECH Tipo Kelch/genética , Neoplasias Hepáticas/genética , Factor 2 Relacionado con NF-E2/genética , Activación Transcripcional , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Redes Reguladoras de Genes , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Mutación , Factor 2 Relacionado con NF-E2/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Pronóstico , Transducción de Señal , Análisis de SupervivenciaRESUMEN
BACKGROUND: Cochineal dyes are used as additives in various foods for the purpose of red coloration. On the other hand, although it has been reported as a causative agent of immediate allergy, most of them are adult women. We report a case of an 8-year-old boy who developed a cochineal allergy.Current disease history: He has been suffering from atopic dermatitis, bronchial asthma, and food allergies since childhood. At the age of seven, he experienced an unknown anaphylaxis reaction twice. When he was 8 years old, he ate a frankfurter containing hypoallergenic cochineal for the first time; cold sweat, intraoral discomfort, respiratory distress, and urticaria appeared throughout the body. His skin prick tests were positive, with a result of 2+to frankfurter and cochineal dyes (color value 0.1 and 0.01). In the immunoblot assay, binding of IgE antibody was observed with CC38K (the main component of cochineal) and a protein of approximately 80-200 kDa in the high molecular weight region. DISCUSSION: We report a case of anaphylaxis with hypoallergenic cochineal onset in a school-age boy.
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Anafilaxia/inducido químicamente , Carmín/efectos adversos , Hipersensibilidad a los Alimentos , Urticaria/inducido químicamente , Niño , Femenino , Humanos , Masculino , Pruebas CutáneasRESUMEN
PRDM14 is overexpressed in various cancers and can regulate cancer phenotype under certain conditions. Inhibiting PRDM14 expression in breast and pancreatic cancers has been reported to reduce cancer stem-like phenotypes, which are associated with aggressive tumor properties. Therefore, PRDM14 is considered a promising target for cancer therapy. To develop a pharmaceutical treatment, the mechanism and interacting partners of PRDM14 need to be clarified. Here, we identified the proteins interacting with PRDM14 in triple-negative breast cancer (TNBC) cells, which do not express the three most common types of receptor (estrogen receptors, progesterone receptors, and HER2). We obtained 13 candidates that were pulled down with PRDM14 in TNBC HCC1937 cells and identified them by mass spectrometry. Two candidates-glucose-regulated protein 78 (GRP78) and heat shock protein 90-α (HSP90α)-were confirmed in immunoprecipitation assay in two TNBC cell lines (HCC1937 and MDA-MB231). Surface plasmon resonance analysis using GST-PRDM14 showed that these two proteins directly interacted with PRDM14 and that the interactions required the C-terminal region of PRDM14, which includes zinc finger motifs. We also confirmed the interactions in living cells by NanoLuc luciferase-based bioluminescence resonance energy transfer (NanoBRET) assay. Moreover, HSP90 inhibitors (17DMAG and HSP990) significantly decreased breast cancer stem-like CD24- CD44+ and side population (SP) cells in HCC1937 cells, but not in PRDM14 knockdown HCC1937 cells. The combination of the GRP78 inhibitor HA15 and PRDM14 knockdown significantly decreased cell proliferation and SP cell number in HCC1937 cells. These results suggest that HSP90α and GRP78 interact with PRDM14 and participate in cancer regulation.
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Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas Represoras/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Proteínas de Unión al ADN , Chaperón BiP del Retículo Endoplásmico , Femenino , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Espectrometría de Masas , Dominios Proteicos , Mapeo de Interacción de Proteínas , Proteínas de Unión al ARN , Proteínas Represoras/química , Resonancia por Plasmón de Superficie , Factores de TranscripciónRESUMEN
Programmed cell death ligand 1 (PD-L1) is expressed on both tumor and tumor-infiltrating nonmalignant cells in lymphoid malignancies. The programmed cell death 1 (PD-1)/PD-L1 pathway suppresses host antitumor responses, although little is known about the significance of PD-1/PD-L1 expression in the tumor microenvironment. To investigate the clinicopathological impact of PD-L1 expression in adult T-cell leukemia/lymphoma (ATLL), we performed PD-L1 immunostaining in 135 ATLL biopsy samples. We observed 2 main groups: 1 had clear PD-L1 expression in lymphoma cells (nPD-L1(+), 7.4% of patients), and the other showed minimal expression in lymphoma cells (nPD-L1(-), 92.6%). Within the nPD-L1(-) group, 2 subsets emerged: the first displayed abundant PD-L1 expression in nonmalignant stromal cells of the tumor microenvironment (miPD-L1(+), 58.5%) and the second group did not express PD-L1 in any cell (PD-L1(-), 34.1%). nPD-L1(+) ATLL (median survival time [MST] 7.5 months, 95% CI [0.4-22.3]) had inferior overall survival (OS) compared with nPD-L1(-) ATLL (MST 14.5 months, 95% CI [10.1-20.0]) (P = .0085). Among nPD-L1(-) ATLL, miPD-L1(+) ATLL (MST 18.6 months, 95% CI [11.0-38.5]) showed superior OS compared with PD-L1(-) ATLL (MST 10.2 months, 95% CI [8.0-14.7]) (P = .0029). The expression of nPD-L1 and miPD-L1 maintained prognostic value for OS in multivariate analysis (P = .0322 and P = .0014, respectively). This is the first report describing the clinicopathological features and outcomes of PD-L1 expression in ATLL. More detailed studies will disclose clinical and biological significance of PD-L1 expression in ATLL.
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Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Leucemia-Linfoma de Células T del Adulto/patología , Células del Estroma/metabolismo , Microambiente Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Leucemia-Linfoma de Células T del Adulto/metabolismo , Leucemia-Linfoma de Células T del Adulto/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Células del Estroma/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND: Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses the ability to proliferate effectively and the potential to differentiate into multiple linages of mesenchymal tissue; similar to adipose-derived stem cells (ASCs). The purpose of this study is to examine the effects of DFAT cell transplantation on cartilage repair in a rat model of osteochondral defects. METHODS: Full-thickness osteochondral defects were created in the knees of Sprague-Dawley rats bilaterally. Cartilage-like micromass pellets were prepared from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently transplanted into the affected right knee of these rats. Defects in the left knee were used as a control. Macroscopic and microscopic changes of treated and control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To observe the transplanted cells, sectioned femurs were immunostained for GFP and type II collagen. RESULTS: DFAT cells formed micromass pellets expressing characteristics of immature cartilage in vitro. In the DFAT cell-transplanted limbs, the defects were completely filled with white micromass pellets as early as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted limbs compared to those of the control limbs. The modified O'Driscol histological scores for the DFAT cell-transplanted limbs were significantly higher than those of the control limbs at corresponding time points. GFP-positive DAFT cells were detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post-operation. CONCLUSIONS: Transplantation of DFAT cell-derived micromass pellets contribute to cartilage repair in a rat osteochondral defect model. DFAT cell transplantation may be a viable therapeutic strategy for the repair of osteochondral injuries.
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Adipocitos/trasplante , Cartílago Articular/lesiones , Cartílago Articular/cirugía , Trasplante de Células/métodos , Animales , Cartílago Articular/patología , Diferenciación Celular , Modelos Animales de Enfermedad , Inmunohistoquímica , Articulación de la Rodilla/patología , Articulación de la Rodilla/cirugía , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
The purpose of the current study was to examine the influence of single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-δ (PPAR-δ), PPAR-γ, and α2 isoforms of the catalytic subunit of AMP-activated protein kinase (PRKAA2) on the extent of changes in anthropometric indices and blood measurements through exercise-centered lifestyle intervention in middle-aged men. A total of 109 Japanese middle-aged male subjects (47.0 ± 0.4 years) participated in the baseline health checkup, 6-month exercise-centered lifestyle intervention, and second checkup conducted several months after the subject completed the intervention. The body mass index (BMI), waist circumference, and clinical measurements, including hemoglobin Alc (HbA1c), triglyceride (TG), alanine aminotransferase (ALT), and γ-glutamyl-transpeptidase (γ-GTP), were measured at the baseline and second checkup. The three SNPs of PPAR-δ A/G (rs2267668), PPAR-γ C/G (rs1801282), and PRKAA2 A/G (rs1418442) were determined. Blunted responses in the reduction in the BMI and waist circumference were observed in A/A carriers of PPAR-δ SNP compared with G allele carriers (all p < 0.05). The A/A carriers also displayed less-marked improvements in HbA1c, TG, ALT, and γ-GTP (all p < 0.05). The current results suggest that A/A carriers of PPAR-δ SNP (rs2267668) may enjoy fewer beneficial effects of exercise-centered lifestyle intervention on anthropometric indices and blood measurements.