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Lipid droplets are important for cancer cell growth and survival. However, the mechanism underlying the initiation of lipid droplet lipolysis is not well understood. We demonstrate here that glucose deprivation induces the binding of choline kinase (CHK) α2 to lipid droplets, which is sequentially mediated by AMPK-dependent CHKα2 S279 phosphorylation and KAT5-dependent CHKα2 K247 acetylation. Importantly, CHKα2 with altered catalytic domain conformation functions as a protein kinase and phosphorylates PLIN2 at Y232 and PLIN3 at Y251. The phosphorylated PLIN2/3 dissociate from lipid droplets and are degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation, and brain tumor growth. In addition, levels of CHKα2 S279 phosphorylation, CHKα2 K247 acetylation, and PLIN2/3 phosphorylation are positively correlated with one another in human glioblastoma specimens and are associated with poor prognosis in glioblastoma patients. These findings underscore the role of CHKα2 as a protein kinase in lipolysis and glioblastoma development.
Assuntos
Colina Quinase/metabolismo , Glioblastoma/enzimologia , Gotículas Lipídicas/enzimologia , Lipólise , Proteínas de Neoplasias/metabolismo , Proteínas Quinases/metabolismo , Acetilação , Linhagem Celular Tumoral , Colina Quinase/genética , Glioblastoma/genética , Humanos , Proteínas de Neoplasias/genética , Proteínas Quinases/genéticaRESUMO
Cancer cells increase lipogenesis for their proliferation and the activation of sterol regulatory element-binding proteins (SREBPs) has a central role in this process. SREBPs are inhibited by a complex composed of INSIG proteins, SREBP cleavage-activating protein (SCAP) and sterols in the endoplasmic reticulum. Regulation of the interaction between INSIG proteins and SCAP by sterol levels is critical for the dissociation of the SCAP-SREBP complex from the endoplasmic reticulum and the activation of SREBPs1,2. However, whether this protein interaction is regulated by a mechanism other than the abundance of sterol-and in particular, whether oncogenic signalling has a role-is unclear. Here we show that activated AKT in human hepatocellular carcinoma (HCC) cells phosphorylates cytosolic phosphoenolpyruvate carboxykinase 1 (PCK1), the rate-limiting enzyme in gluconeogenesis, at Ser90. Phosphorylated PCK1 translocates to the endoplasmic reticulum, where it uses GTP as a phosphate donor to phosphorylate INSIG1 at Ser207 and INSIG2 at Ser151. This phosphorylation reduces the binding of sterols to INSIG1 and INSIG2 and disrupts the interaction between INSIG proteins and SCAP, leading to the translocation of the SCAP-SREBP complex to the Golgi apparatus, the activation of SREBP proteins (SREBP1 or SREBP2) and the transcription of downstream lipogenesis-related genes, proliferation of tumour cells, and tumorigenesis in mice. In addition, phosphorylation of PCK1 at Ser90, INSIG1 at Ser207 and INSIG2 at Ser151 is not only positively correlated with the nuclear accumulation of SREBP1 in samples from patients with HCC, but also associated with poor HCC prognosis. Our findings highlight the importance of the protein kinase activity of PCK1 in the activation of SREBPs, lipogenesis and the development of HCC.
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Carcinoma Hepatocelular/metabolismo , Gluconeogênese , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lipogênese , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Animais , Carcinogênese , Carcinoma Hepatocelular/patologia , Proliferação de Células , Modelos Animais de Doenças , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/química , Camundongos , Camundongos Nus , Oxisteróis/metabolismo , Fosforilação , Prognóstico , Ligação Proteica , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismoRESUMO
EGFR activates phosphatidylinositide 3-kinase (PI3K), but the mechanism underlying this activation is not completely understood. We demonstrated here that EGFR activation resulted in lysine acetyltransferase 5 (KAT5)-mediated K395 acetylation of the platelet isoform of phosphofructokinase 1 (PFKP) and subsequent translocation of PFKP to the plasma membrane, where the PFKP was phosphorylated at Y64 by EGFR. Phosphorylated PFKP binds to the N-terminal SH2 domain of p85α, which is distinct from binding of Gab1 to the C-terminal SH2 domain of p85α, and recruited p85α to the plasma membrane resulting in PI3K activation. PI3K-dependent AKT activation results in enhanced phosphofructokinase 2 (PFK2) phosphorylation and production of fructose-2,6-bisphosphate, which in turn promotes PFK1 activation. PFKP Y64 phosphorylation-enhanced PI3K/AKT-dependent PFK1 activation and GLUT1 expression promoted the Warburg effect, tumor cell proliferation, and brain tumorigenesis. These findings underscore the instrumental role of PFKP in PI3K activation and enhanced glycolysis through PI3K/AKT-dependent positive-feedback regulation.
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Neoplasias Encefálicas/enzimologia , Glioblastoma/enzimologia , Glicólise , Fosfatidilinositol 3-Quinases/metabolismo , Fosfofrutoquinase-1 Tipo C/metabolismo , Acetilação , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Classe Ia de Fosfatidilinositol 3-Quinase , Ativação Enzimática , Receptores ErbB/genética , Receptores ErbB/metabolismo , Retroalimentação Fisiológica , Frutosedifosfatos/metabolismo , Glioblastoma/genética , Glioblastoma/patologia , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Humanos , Lisina Acetiltransferase 5/genética , Lisina Acetiltransferase 5/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/genética , Fosfofrutoquinase-1 Tipo C/genética , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo , Fosforilação , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Domínios de Homologia de srcRESUMO
Autophagy is crucial for maintaining cell homeostasis. However, the precise mechanism underlying autophagy initiation remains to be defined. Here, we demonstrate that glutamine deprivation and hypoxia result in inhibition of mTOR-mediated acetyl-transferase ARD1 S228 phosphorylation, leading to ARD1-dependent phosphoglycerate kinase 1 (PGK1) K388 acetylation and subsequent PGK1-mediated Beclin1 S30 phosphorylation. This phosphorylation enhances ATG14L-associated class III phosphatidylinositol 3-kinase VPS34 activity by increasing the binding of phosphatidylinositol to VPS34. ARD1-dependent PGK1 acetylation and PGK1-mediated Beclin1 S30 phosphorylation are required for glutamine deprivation- and hypoxia-induced autophagy and brain tumorigenesis. Furthermore, PGK1 K388 acetylation levels correlate with Beclin1 S30 phosphorylation levels and poor prognosis in glioblastoma patients. Our study unearths an important mechanism underlying cellular-stress-induced autophagy initiation in which the protein kinase activity of the metabolic enzyme PGK1 plays an instrumental role and reveals the significance of the mutual regulation of autophagy and cell metabolism in maintaining cell homeostasis.
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Autofagossomos/enzimologia , Autofagia , Proteína Beclina-1/metabolismo , Neoplasias Encefálicas/enzimologia , Glioblastoma/enzimologia , Fosfoglicerato Quinase/metabolismo , Acetilação , Animais , Autofagossomos/patologia , Proteína Beclina-1/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Classe III de Fosfatidilinositol 3-Quinases/genética , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Glutamina/deficiência , Células HEK293 , Humanos , Camundongos Nus , Acetiltransferase N-Terminal A/genética , Acetiltransferase N-Terminal A/metabolismo , Acetiltransferase N-Terminal E/genética , Acetiltransferase N-Terminal E/metabolismo , Fosfoglicerato Quinase/genética , Fosforilação , Ligação Proteica , Interferência de RNA , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Transfecção , Carga Tumoral , Hipóxia TumoralRESUMO
Overcoming metabolic stress is a critical step in tumor growth. Acetyl coenzyme A (acetyl-CoA) generated from glucose and acetate uptake is important for histone acetylation and gene expression. However, how acetyl-CoA is produced under nutritional stress is unclear. We demonstrate here that glucose deprivation results in AMP-activated protein kinase (AMPK)-mediated acetyl-CoA synthetase 2 (ACSS2) phosphorylation at S659, which exposed the nuclear localization signal of ACSS2 for importin α5 binding and nuclear translocation. In the nucleus, ACSS2 binds to transcription factor EB and translocates to lysosomal and autophagy gene promoter regions, where ACSS2 incorporates acetate generated from histone acetylation turnover to locally produce acetyl-CoA for histone H3 acetylation in these regions and promote lysosomal biogenesis, autophagy, cell survival, and brain tumorigenesis. In addition, ACSS2 S659 phosphorylation positively correlates with AMPK activity in glioma specimens and grades of glioma malignancy. These results underscore the significance of nuclear ACSS2-mediated histone acetylation in maintaining cell homeostasis and tumor development.
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Acetato-CoA Ligase/metabolismo , Autofagia , Neoplasias Encefálicas/enzimologia , Núcleo Celular/enzimologia , Glioblastoma/enzimologia , Histonas/metabolismo , Lisossomos/metabolismo , Biogênese de Organelas , Transcrição Gênica , Proteínas Quinases Ativadas por AMP/metabolismo , Acetato-CoA Ligase/genética , Acetilcoenzima A/metabolismo , Acetilação , Transporte Ativo do Núcleo Celular , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Sítios de Ligação , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Núcleo Celular/patologia , Sobrevivência Celular , Metabolismo Energético , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação , Regiões Promotoras Genéticas , Ligação Proteica , Processamento de Proteína Pós-Traducional , Interferência de RNA , Estresse Fisiológico , Transfecção , alfa Carioferinas/genética , alfa Carioferinas/metabolismoRESUMO
This study presents findings indicating that the ferroelectric tunnel junction (FTJ) or resistive random-access memory (RRAM) in one cell can be intentionally selected depending on the application. The HfAlO film annealed at 700 °C shows stable FTJ characteristics and can be converted into RRAM by forming a conductive filament inside the same cell, that is, the process of intentionally forming a conductive filament is the result of defect generation and redistribution, and applying compliance current prior to a hard breakdown event of the dielectric film enables subsequent RRAM operation. The converted RRAM demonstrated good memory performance. Through current-voltage fitting, it was confirmed that the two resistance states of the FTJ and RRAM had different transport mechanisms. In the RRAM, the 1/f noise power of the high-resistance state (HRS) was about ten times higher than that of the low-resistance state (LRS). This is because the noise components increase due to the additional current paths in the HRS. The 1/f noise power according to resistance states in the FTJ was exactly the opposite result from the case of the RRAM. This is because the noise component due to the Poole-Frenkel emission is added to the noise component due to the tunneling current in the LRS. In addition, we confirmed the potentiation and depression characteristics of the two devices and further evaluated the accuracy of pattern recognition through a simulation by considering a dataset from the Modified National Institute of Standards and Technology.
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Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity (p-value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.
Assuntos
Malformações Arteriovenosas , Biomarcadores , Células Endoteliais , MicroRNAs , Fator A de Crescimento do Endotélio Vascular , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/metabolismo , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/diagnóstico , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Masculino , Feminino , Adulto , Hipóxia Celular/genéticaRESUMO
BACKGROUND: Oral potentially malignant disorders (OPMDs) are associated with an increased risk of cancer of the oral cavity including the tongue. The early detection of oral cavity cancers and OPMDs is critical for reducing cancer-specific morbidity and mortality. Recently, there have been studies to apply the rapidly advancing technology of deep learning for diagnosing oral cavity cancer and OPMDs. However, several challenging issues such as class imbalance must be resolved to effectively train a deep learning model for medical imaging classification tasks. The aim of this study is to evaluate a new technique of artificial intelligence to improve the classification performance in an imbalanced tongue lesion dataset. METHODS: A total of 1,810 tongue images were used for the classification. The class-imbalanced dataset consisted of 372 instances of cancer, 141 instances of OPMDs, and 1,297 instances of noncancerous lesions. The EfficientNet model was used as the feature extraction model for classification. Mosaic data augmentation, soft labeling, and curriculum learning (CL) were employed to improve the classification performance of the convolutional neural network. RESULTS: Utilizing a mosaic-augmented dataset in conjunction with CL, the final model achieved an accuracy rate of 0.9444, surpassing conventional oversampling and weight balancing methods. The relative precision improvement rate for the minority class OPMD was 21.2%, while the relative [Formula: see text] score improvement rate of OPMD was 4.9%. CONCLUSIONS: The present study demonstrates that the integration of mosaic-based soft labeling and curriculum learning improves the classification performance of tongue lesions compared to previous methods, establishing a foundation for future research on effectively learning from imbalanced data.
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Aprendizado Profundo , Neoplasias Bucais , Humanos , Inteligência Artificial , Currículo , LínguaRESUMO
Green ammonia is an efficient, carbon-free energy carrier and storage medium. The ammonia synthesis using green hydrogen requires an active catalyst that operates under mild conditions. The catalytic activity can be promoted by controlling the geometry and electronic structure of the active species. An exsolution process is implemented to improve catalytic activity by modulating the geometry and electronic structure of Ru. Ru nanoparticles exsolved on a BaCe0.9 Y0.1 O3-δ support exhibit uniform size distribution, 5.03 ± 0.91 nm, and exhibited one of the highest activities, 387.31 mmolNH3 gRu -1 h-1 (0.1 MPa and 450 °C). The role of the exsolution and BaCe0.9 Y0.1 O3-δ support is studied by comparing the catalyst with control samples and in-depth characterizations. The optimal nanoparticle size is maintained during the reaction, as the Ru nanoparticles prepared by exsolution are well-anchored to the support with in-plane epitaxy. The electronic structure of Ru is modified by unexpected in situ Ba promoter accumulation around the base of the Ru nanoparticles.
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The study aimed to revalidate the influence of WBCs on chronic disease risk factors and to verify which markers are independently involved in WBC level changes in a Korean population. A total of 80 Korean subjects were divided into three groups, according to the WBC count: mild decrease in WBC, normal WBC, and mild increase in WBC. Fasting blood samples for analyzing biochemical parameters and inflammatory markers were obtained from the subjects, and their body fat composition was evaluated by dual energy x-ray absorptiometry and computed tomography. The WBC levels were related to levels of adiponectin, triglyceride, and insulin, which are associated with the risk of chronic diseases. In the mild increase in WBC group, high-sensitivity C-reactive protein (hs-CRP) and TNF-α levels increased, and s.c. fat area at the first lumbar vertebrae and fourth lumbar vertebrae decreased. The WBC count positively correlated with hs-CRP and TNF-α levels and most of the body fat composition data, evaluated by dual energy x-ray absorptiometry and computed tomography. Notably, hs-CRP and TNF-α levels, fat mass, and visceral-to-s.c. fat area ratio at the first lumbar vertebrae were revealed as independent predictors of WBC level change. Finally, the receiver operating characteristic curve analysis showed that the additional use of body fat composition data with the conventional inflammatory markers reliably enhanced the predictive capacity of WBC level changes. Thus, we suggest that by controlling inflammatory markers and body fat composition, WBC levels can be kept within a range that is safe from the risk of chronic diseases.
Assuntos
Tecido Adiposo/metabolismo , Composição Corporal/fisiologia , Leucócitos/metabolismo , Leucócitos/fisiologia , Adiponectina/metabolismo , Adulto , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Doença Crônica , Feminino , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade , Adulto JovemRESUMO
Histone modifications, such as the frequently occurring lysine succinylation, are central to the regulation of chromatin-based processes. However, the mechanism and functional consequences of histone succinylation are unknown. Here we show that the α-ketoglutarate dehydrogenase (α-KGDH) complex is localized in the nucleus in human cell lines and binds to lysine acetyltransferase 2A (KAT2A, also known as GCN5) in the promoter regions of genes. We show that succinyl-coenzyme A (succinyl-CoA) binds to KAT2A. The crystal structure of the catalytic domain of KAT2A in complex with succinyl-CoA at 2.3 Å resolution shows that succinyl-CoA binds to a deep cleft of KAT2A with the succinyl moiety pointing towards the end of a flexible loop 3, which adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Site-directed mutagenesis indicates that tyrosine 645 in this loop has an important role in the selective binding of succinyl-CoA over acetyl-CoA. KAT2A acts as a succinyltransferase and succinylates histone H3 on lysine 79, with a maximum frequency around the transcription start sites of genes. Preventing the α-KGDH complex from entering the nucleus, or expression of KAT2A(Tyr645Ala), reduces gene expression and inhibits tumour cell proliferation and tumour growth. These findings reveal an important mechanism of histone modification and demonstrate that local generation of succinyl-CoA by the nuclear α-KGDH complex coupled with the succinyltransferase activity of KAT2A is instrumental in histone succinylation, tumour cell proliferation, and tumour development.
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Histona Acetiltransferases/metabolismo , Histonas/metabolismo , Complexo Cetoglutarato Desidrogenase/metabolismo , Acetilcoenzima A/metabolismo , Acil Coenzima A/metabolismo , Animais , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células , Cristalografia por Raios X , Feminino , Regulação da Expressão Gênica , Histona Acetiltransferases/química , Histona Acetiltransferases/genética , Histonas/química , Humanos , Lisina/metabolismo , Camundongos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Neoplasias/enzimologia , Neoplasias/metabolismo , Neoplasias/patologia , Ligação Proteica , Domínios Proteicos , Sítio de Iniciação de Transcrição , Tirosina/genética , Tirosina/metabolismoRESUMO
BACKGROUND: Surgical management for chondrosarcoma of the temporomandibular joint (TMJ) is challenging due to the anatomical location involving the facial nerve and the functional joint. The purpose of this case series was to analyze the largest number of TMJ chondrosarcoma cases reported from a single institution and to review the literature about chondrosarcoma involving the TMJ. METHODS: Ten TMJ chondrosarcoma patients at Seoul National University Dental Hospital were included in this study. Radiographic features, surgical approaches, histopathologic subtypes, and treatment modalities were evaluated. All case reports of TMJ chondrosarcoma published in English from 1954 to 2021 were collected under PRISMA guidelines and comprehensively reviewed. RESULTS: The lesions were surgically resected in all 10 patients with efforts to preserve facial nerve function. Wide excision including margins of normal tissue was performed to ensure adequate resection margins. All TMJs were reconstructed with a metal condyle except one, which was reconstructed with vascularized costal bone. At last follow-up, all patients were still alive, and there had been no recurrence. Among 47 cases (patients from the literature and our cases), recurrence was specified in 43 and occurred in four (9.5%). CONCLUSIONS: For surgical management of TMJ chondrosarcoma, wide excision must consider preservation of the facial nerve. Reconstruction using a metal condyle prosthesis and a vascularized free flap is reliable. A more conservative surgical approach correlates with a favorable prognosis for facial nerve recovery. Nevertheless, wide excision is imperative to prevent tumor recurrence. In cases in which the glenoid fossa is unaffected by the tumor, it is deemed unnecessary to reconstruct the glenoid fossa within an oncological setting.
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Neoplasias Ósseas , Condrossarcoma , Retalhos de Tecido Biológico , Humanos , Recidiva Local de Neoplasia/cirurgia , Condrossarcoma/cirurgia , Margens de Excisão , Neoplasias Ósseas/cirurgiaRESUMO
The purpose of this study was to classify and characterize facial asymmetry (FA) phenotypes in adult patients with unilateral cleft lip and palate (UCLP) and skeletal class III malocclusion. The samples comprised 52 adult UCLP patients (36 men and 16 women; mean age, 22.43 y) who had undergone orthognathic surgery for correction of class III malocclusion. After measurement of 22 cephalometric parameters in posteroanterior cephalograms taken 1 month before orthognathic surgery, principal component analysis was performed to obtain 5 representative parameters [deviation (mm) of ANS (ANS-dev), maxillary central incisor contact point (Mx1-dev), and menton (Me-dev); cant (degree) of the maxillary anterior occlusal plane (MxAntOP-cant) and mandibular border (MnBorder-cant)]. K-means cluster analysis was conducted using these representative parameters. The differences in cephalometric parameters among the clusters were statistically analyzed. The FA phenotypes were classified into 4 types: No-cant-and-No-deviation type (cluster-4, n=16, 30.8%); MxMn-cant-MxMn-dev to the cleft-side type (cluster-3, n=4, 7.7%); Mx-cant-Mn-shift to the cleft-side type (cluster-2, n=15, 28.8%); and Mn-cant-Mn-dev to the noncleft-side type (cluster-1, n=17, 32.7%). Asymmetry in the maxilla and/or mandible were observed in 70% of patients. One third of patients (cluster-2 and cluster-3; sum, 36.5%) exhibited significant cant of MxAntOP induced by cleft and cant or shift of the mandible to the cleft side. Another one third of patients (cluster-1, 32.7%) demonstrated significant deviation and cant of the mandible to the noncleft-side despite cleft in the maxilla. This FA phenotype classification might be a basic guideline for diagnosis and treatment planning for UCLP patients.
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Fenda Labial , Fissura Palatina , Má Oclusão Classe III de Angle , Feminino , Humanos , Fenda Labial/cirurgia , Assimetria Facial/cirurgia , Fissura Palatina/cirurgia , Análise de Componente Principal , Estudos Retrospectivos , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , Maxila/cirurgia , CefalometriaRESUMO
The purpose of this study was to classify the skeletal phenotypes of adult patients with skeletal class III (C-III) malocclusion and unilateral or bilateral cleft lip and palate using principal component analysis and cluster analysis. The samples consisted of 81 adult C-III patients with cleft lip and palate (CLP) who underwent orthognathic surgery (OGS) or distraction osteogenesis (59 males and 22 females; 50 unilateral cleft lip and palate and 31 bilateral cleft lip and palate; mean age when lateral cephalograms were taken, 22.2±4.6 y). Thirteen angular and one ratio cephalometric variables were measured. Using 4 representative variables obtained from principal component analysis (SNA, SNB, Gonial angle, and Bjork sum), K-means cluster analysis was performed to classify the phenotypes. Then, statistical analysis was conducted to characterize the differences in the variables among the clusters. Five clusters were obtained from 3 groups: severely retrusive maxilla and moderately retrusive mandible group: cluster-1 (23.5%, severely hyperdivergent pattern), cluster-4 (27.2%, moderately hyperdivergent pattern), and cluster-5 (11.1%, normodivergent pattern); moderately retrusive maxilla and normal mandible group: cluster-2 (30.9%, normodivergent pattern); normal maxilla and moderately protrusive mandible group: cluster-3 (7.4%, normodivergent pattern). Although skeletal phenotypes were diverse, distribution of sex and cleft type did not differ among 5 clusters ( P >0.05). Sixty-two percent of cleft patients showed a severely retrusive maxilla and moderately retrusive mandible (cluster-1, cluster-4, and cluster-5), which indicated that these are the main cause of skeletal C-III malocclusion in CLP patients who were treated with OGS. Therefore, it is necessary to consider presurgical orthodontic treatment and surgical planning based on the skeletal phenotypes of CLP patients.
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Fenda Labial , Fissura Palatina , Má Oclusão Classe III de Angle , Masculino , Feminino , Humanos , Adulto , Fenda Labial/cirurgia , Fenda Labial/complicações , Fissura Palatina/cirurgia , Fissura Palatina/complicações , Análise de Componente Principal , Má Oclusão Classe III de Angle/cirurgia , Má Oclusão Classe III de Angle/etiologia , Mandíbula/cirurgia , Maxila/cirurgia , CefalometriaRESUMO
INTRODUCTION: Monitoring metabolic biomarkers could be utilized as an effective tool for the early detection of gastric cancer (GC) risk. OBJECTIVE: We aimed to discover predictive serum biomarkers for GC and investigate biomarker-related metabolism. METHODS: Subjects were randomly selected from the Korean Cancer Prevention Study-II cohort and matched by age and sex. We analyzed baseline serum samples of 160 subjects (discovery set; control and GC occurrence group, 80 each) via nontargeted screening. Identified putative biomarkers were validated in baseline serum samples of 140 subjects (validation set; control and GC occurrence group, 70 each) using targeted metabolites analysis. RESULTS: The final analysis was conducted on the discovery set (control, n = 52 vs. GC occurrence, n = 50) and the validation set (control, n = 43 vs. GC occurrence, n = 44) applying exclusion conditions. Eighteen putative metabolite sets differed between two groups found on nontargeted metabolic screening. We focused on fatty acid-related energy metabolism. In targeted analysis, levels of decanoyl-L-carnitine (p = 0.019), L-carnitine (p = 0.033), and citric acid (p = 0.025) were significantly lower in the GC occurrence group, even after adjusting for age, sex, and smoking status. Additionally, L-carnitine and citric acid were confirmed to have an independently significant relationship to GC development. Notably, alkaline phosphatase showed a significant correlation with these two biomarkers. CONCLUSION: Changes in serum L-carnitine and citric acid levels that may result from alterations of fatty-acid-related energy metabolism are expected to be valuable biomarkers for the early diagnosis of GC risk.
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Neoplasias Gástricas , Fosfatase Alcalina , Biomarcadores , Carnitina , Ácido Cítrico , Humanos , Metabolômica , República da Coreia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismoRESUMO
Legumes are rich sources of essential nutrients, and their potential health benefits were reported in many studies. Several studies showed a positive effect of legumes on obesity, but randomised clinical trials are limited in the Korean population. The present intervention study investigated the impact of legumes on body weight in obese Korean subjects. A total of 400 participants (BMI ≥ 25 kg/m2) were randomised into two groups. The legume-enriched diet (LD) group replaced one-third of their refined rice consumption with legumes three times per day as a carbohydrate source. In contrast, the usual diet (UD) group consumed their UD. The mean weight loss at 12 weeks was 2·87 (sem 0·21) kg and 0·17 (sem 0·11) kg in the LD and UD, respectively, which was significantly different between the groups (P < 0·001). HDL-cholesterol and adiponectin levels were increased, and levels of glucose, insulin, TAG, and 8-epi-PGF2α and the homoeostasis model assessment of insulin resistance (IR) index value decreased at 12 weeks compared with baseline in the LD. The consumption of legumes may accelerate weight loss accompanied by regulation of adiponectin and 8-epi-PGF2α in obese subjects. In particular, legumes seemed to induce significant changes in BMI by increasing adiponectin in females. Additionally, increases in plasma adiponectin due to greater substantial weight loss may be related to the improvement in IR.
Assuntos
Fabaceae , Resistência à Insulina , Adiponectina , Glicemia , Índice de Massa Corporal , Feminino , Humanos , Fator de Crescimento Placentário , Prostaglandinas F , Redução de Peso/fisiologiaRESUMO
BACKGROUND: Discoidin domain receptor 1 (DDR1), a member of receptor tyrosine kinase, has been implicated in tumor progression. However, the function and underlying mechanism of DDR1 in lung adenocarcinoma (LUAD) progression is unclear. Thus, we explored the molecular regulatory mechanism of DDR1 in the migration of LUAD. METHODS: Transwell assays, wound healing assays and xenograft tumor assays were performed to study the function of DDR1 in the progression of LUAD. Immunoblotting and quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression levels of genes. Co-immunoprecipitation (co-IP) assays were performed to detect the interaction between DDR1 and AKT. Immunofluorescence and immunohistochemistry assays were used to determine the expression level of proteins in cells and tissues, respectively. RESULTS: DDR1 expression was significantly higher in LUAD tissues than in normal lung tissues, and the level of DDR1 was inversely correlated with prognosis in patients. We found that DDR1 promoted the migration and invasion of LUAD cells in vitro. Furthermore, ectopic expression of DDR1 in LUAD cells altered EMT-related markers expression. Importantly, the DDR1 protein interacted with AKT and phosphorylated AKT. The AKT inhibitor MK2206 interrupted Snail upregulation in DDR1-overexpressing LUAD cells. Finally, our study revealed that depletion of DDR1 attenuated LUAD cell migration in a tumor xenograft mouse model. CONCLUSION: Our findings uncovered that a high abundance of DDR1 increased the migration and invasion capability of LUAD cells via the AKT/Snail signaling axis and indicated that DDR1 could be a potential target for treating LUAD.
Assuntos
Adenocarcinoma de Pulmão , Receptor com Domínio Discoidina 1 , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-akt , Fatores de Transcrição da Família Snail , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Receptor com Domínio Discoidina 1/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética , Fatores de Transcrição da Família Snail/genéticaRESUMO
BACKGROUND: SARS-CoV-2 rapid antigen test can supplement the nucleic acid amplification method. METHODS: We calculated the sensitivity and specificity of the GenBody COVID-19 antigen assay using 155 nasopharyngeal specimens. RESULTS: The sensitivity in samples with their respective cycle thresholds varied from 33.3% to 100%; the sensitivity of the antigen assay was inferior to that of the gold standard polymerase chain reaction test. CONCLUSIONS: Considering the relatively fast speed of the antigen test and high sensitivity at a low cycle threshold value indicating a high viral load, the GenBody COVID-19 antigen test can be an easy and quick measure for detecting SARS-CoV-2 in individuals with high viral loads.
Assuntos
COVID-19 , SARS-CoV-2 , Antígenos Virais/genética , COVID-19/diagnóstico , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: We investigate the performance of new hydrophobic diffractive multifocal intraocular lenses (IOL) with hydroxyethyl methacrylate (HEMA) and compare their optical quality, contrast sensitivity, and subjective photic phenomena. METHODS: Medical records of patients who underwent routine simple cataract surgery and insertion of an existing multifocal IOL (TFNT, TF group) or a new multifocal IOL (CNWT, CN group) were retrospectively reviewed. Clinical data was collected 2 months postoperatively and included optical quality analysis system (OQAS) indices, contrast sensitivity, and subjective degrees of photic phenomena. RESULTS: One hundred thirty-five eyes of 135 patients were included (CN group, 71; TF group, 64). There was no significant difference between the two groups in the visual acuity and defocus curve. The indices of OQAS did not show a significant difference between groups. Contrast sensitivity was significantly better in the CN group at all degrees, including the area under the log contrast sensitivity function (p = 0.01). The subjective photic phenomena survey showed better results for the CN group, with the proportion of patients reporting no photic phenomena as 9.9% and 3.1% in the CN and TF groups, respectively. The proportion of patients who reported severe photic phenomena was 11.3% in the CN group and 25.0% in the TF group. Although the follow-up period was only 2 months, glistening, surface scattering, and posterior capsule opacity were not observed in any patient. CONCLUSIONS: The new multifocal IOL with HEMA is safe, and provides stable visual acuity as well as superior contrast sensitivity and lower subjective photic phenomena, over the prior IOL.
Assuntos
Lentes Intraoculares , Lentes Intraoculares Multifocais , Facoemulsificação , Sensibilidades de Contraste , Humanos , Implante de Lente Intraocular/métodos , Metacrilatos , Estudos Prospectivos , Desenho de Prótese , Pseudofacia , Estudos RetrospectivosRESUMO
Background: A combination of the reduction mammoplasty technique and breast reconstruction allows surgeons to lift ptotic breasts through local flaps and skin reduction during surgery for breast cancer. This study presents a reliable course for the combination of partial and skin or nipple-sparing mastectomy with reduction-reconstruction surgery. Methods: Fifty-seven patients underwent a partial mastectomy before reduction mammoplasty of both breasts during the same time period between 2014 and 2021 at our institution and thirteen patients underwent skin or nipple-sparing mastectomy, breast reconstruction with an extended latissimus dorsi flap or silicone implant, and aesthetic reduction mammoplasty of the contralateral breast during the same time period. Additional photos were obtained preoperatively, immediately after the operation, and at one, three, six, and twelve months postoperatively. Patient satisfaction was evaluated preoperatively and postoperatively and postoperative complications were noted. Results: Among the patients who underwent a partial mastectomy, the mean age was 45.18 ± 11.05 years, the mean body mass index (BMI) was 26.74 ± 3.53 kg/m2, and the mean preoperative right and left breast volumes were 663.85 (±28.12) cc and 664.34 (±37.13) cc, respectively, and the mean excised mass weight was 177.74 (±213.93) g. Among the patients who underwent a skin-sparing mastectomy, the mean age was 51.62 ± 8.96 years, the mean BMI was 26.91 ± 4.34 kg/m2, and the mean preoperative right and left breast volumes were 624.17 (±98.52) cc and 562.31 (±80.81) cc, respectively, and the mean excised mass weight was 618.05 (±338.17) g. Four patients (5.3%) in the partial mastectomy group had fat necrosis. The mean patient satisfaction score was higher postoperatively in both groups. Conclusion: Patients with breast cancer and large and/or ptotic breasts can successfully undergo reduction mammoplasty for both breasts immediately following partial mastectomy and nipple or skin-sparing mastectomy.