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1.
PLoS Pathog ; 19(1): e1011095, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36630443

RESUMO

G-quadruplex (G4) formed by repetitive guanosine-rich sequences plays important roles in diverse cellular processes; however, its roles in viral infection are not fully understood. In this study, we investigated the genome-wide distribution of G4-forming sequences (G4 motifs) in Varicella-Zoster virus (VZV) and found that G4 motifs are enriched in the internal repeat short and the terminal repeat short regions flanking the unique short region and also in some reiteration (R) sequence regions. A high density of G4 motifs in the R2 region was found on the template strand of ORF14, which encodes glycoprotein C (gC), a virulent factor for viral growth in skin. Analyses such as circular dichroism spectroscopy, thermal difference spectra, and native polyacrylamide gel electrophoresis with oligodeoxynucleotides demonstrated that several G4 motifs in ORF14 form stable G4 structures. In transfection assays, gC expression from the G4-disrupted ORF14 gene was increased at the transcriptional level and became more resistant to suppression by G4-ligand treatment. The recombinant virus containing the G4-disrupted ORF14 gene expressed a higher level of gC mRNA, while it showed a slightly reduced growth. This G4-disrupted ORF14 virus produced smaller plaques than the wild-type virus. Our results demonstrate that G4 formation via reiteration sequences suppresses gC expression during VZV infection and regulates viral cell-to-cell spread.


Assuntos
Quadruplex G , Herpesvirus Humano 3/genética , Proteínas do Envelope Viral/genética , Genoma , Dicroísmo Circular
2.
J Med Virol ; 96(3): e29504, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38445794

RESUMO

While most NOD-like receptors (NLRs) are predominately expressed by innate immune cells, NLRC3, an inhibitory NLR of immune signaling, exhibits the highest expression in lymphocytes. The role of NLRC3 or any NLRs in B lymphocytes is completely unknown. Gammaherpesviruses, including human Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV-68), establish latent infection in B lymphocytes, which requires elevated NF-κB. This study shows that during latent EBV infection of human B cells, viral-encoded latent membrane protein 1 (LMP1) decreases NLRC3 transcript. LMP1-induced-NF-κB activation suppresses the promoter activity of NLRC3 via p65 binding to the promoter. Conversely, NLRC3 inhibits NF-κB activation by promoting the degradation of LMP1 in a proteasome-dependent manner. In vivo, MHV-68 infection reduces Nlrc3 transcripts in splenocytes, and Nlrc3-deficient mice show greater viral latency than controls. These results reveal a bidirectional regulatory circuit in B lymphocytes, where viral latent protein LMP1 reduces NLRC3 expression, while NLRC3 disrupts gammaherpesvirus latency, which is an important step for tumorigenesis.


Assuntos
Infecções por Vírus Epstein-Barr , Latência Viral , Animais , Humanos , Camundongos , Herpesvirus Humano 4/genética , NF-kappa B , Linfócitos B , Peptídeos e Proteínas de Sinalização Intercelular
3.
Plant Cell Rep ; 43(7): 164, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38852113

RESUMO

KEY MESSAGE: Hyperspectral features enable accurate classification of soybean seeds using linear discriminant analysis and GWAS for novel seed trait genes. Evaluating crop seed traits such as size, shape, and color is crucial for assessing seed quality and improving agricultural productivity. The introduction of the SUnSet toolbox, which employs hyperspectral sensor-derived image analysis, addresses this necessity. In a validation test involving 420 seed accessions from the Korean Soybean Core Collections, the pixel purity index algorithm identified seed- specific hyperspectral endmembers to facilitate segmentation. Various metrics extracted from ventral and lateral side images facilitated the categorization of seeds into three size groups and four shape groups. Additionally, quantitative RGB triplets representing seven seed coat colors, averaged reflectance spectra, and pigment indices were acquired. Machine learning models, trained on a dataset comprising 420 accession seeds and 199 predictors encompassing seed size, shape, and reflectance spectra, achieved accuracy rates of 95.8% for linear discriminant analysis model. Furthermore, a genome-wide association study utilizing hyperspectral features uncovered associations between seed traits and genes governing seed pigmentation and shapes. This comprehensive approach underscores the effectiveness of SUnSet in advancing precision agriculture through meticulous seed trait analysis.


Assuntos
Glycine max , Fenótipo , Sementes , Glycine max/genética , Sementes/genética , Sementes/anatomia & histologia , Estudo de Associação Genômica Ampla/métodos , Imageamento Hiperespectral/métodos , Pigmentação/genética , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Aprendizado de Máquina
4.
Int J Mol Sci ; 25(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892434

RESUMO

Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood-immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.


Assuntos
Receptores ErbB , Proteínas Proto-Oncogênicas c-bcl-2 , Pontos Quânticos , RNA Interferente Pequeno , Pontos Quânticos/química , Animais , Receptores ErbB/genética , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Humanos , RNA Interferente Pequeno/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Camundongos , Linhagem Celular Tumoral , Nanopartículas/química , Lipídeos/química , Nanomedicina Teranóstica/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Micelas
5.
Int J Mol Sci ; 25(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38339090

RESUMO

Combining standard surgical procedures with personalized chemotherapy and the continuous monitoring of cancer progression is necessary for effective NSCLC treatment. In this study, we developed liposomal nanoparticles as theranostic agents capable of simultaneous therapy for and imaging of target cancer cells. Copper-64 (64Cu), with a clinically practical half-life (t1/2 = 12.7 h) and decay properties, was selected as the radioisotope for molecular PET imaging. An anti-epidermal growth factor receptor (anti-EGFR) antibody was used to achieve target-specific delivery. Simultaneously, the chemotherapeutic agent doxorubicin (Dox) was encapsulated within the liposomes using a pH-gradient method. The conjugates of 64Cu-labeled and anti-EGFR antibody-conjugated micelles were inserted into the doxorubicin-encapsulating liposomes via a post-insertion procedure (64Cu-Dox-immunoliposomes). We evaluated the size and zeta-potential of the liposomes and analyzed target-specific cell binding and cytotoxicity in EGFR-positive cell lines. Then, we analyzed the specific therapeutic effect and PET imaging of the 64Cu-Dox-immunoliposomes with the A549 xenograft mouse model. In vivo therapeutic experiments on the mouse models demonstrated that the doxorubicin-containing 64Cu-immunoliposomes effectively inhibited tumor growth. Moreover, the 64Cu-immunoliposomes provided superior in vivo PET images of the tumors compared to the untargeted liposomes. We suggest that nanoparticles will be the potential platform for cancer treatment as a widely applicable theranostic system.


Assuntos
Radioisótopos de Cobre , Doxorrubicina , Lipossomos , Neoplasias , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Cobre , Doxorrubicina/uso terapêutico , Doxorrubicina/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Receptores ErbB/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Polietilenoglicóis , Tomografia por Emissão de Pósitrons , Medicina de Precisão
6.
Int J Mol Sci ; 25(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38338667

RESUMO

mRNA vaccines have emerged as a pivotal tool in combating COVID-19, offering an advanced approach to immunization. A key challenge with these vaccines is their need for extremely-low-temperature storage, which affects their stability and shelf life. Our research addresses this issue by enhancing the stability of mRNA vaccines through a novel cationic lipid, O,O'-dimyristyl-N-lysyl aspartate (DMKD). DMKD effectively binds with mRNA, improving vaccine stability. We also integrated phosphatidylserine (PS) into the formulation to boost immune response by promoting the uptake of these nanoparticles by immune cells. Our findings reveal that DMKD-PS nanoparticles maintain structural integrity under long-term refrigeration and effectively protect mRNA. When tested, these nanoparticles containing green fluorescent protein (GFP) mRNA outperformed other commercial lipid nanoparticles in protein expression, both in immune cells (RAW 264.7 mouse macrophage) and non-immune cells (CT26 mouse colorectal carcinoma cells). Importantly, in vivo studies show that DMKD-PS nanoparticles are safely eliminated from the body within 48 h. The results suggest that DMKD-PS nanoparticles present a promising alternative for mRNA vaccine delivery, enhancing both the stability and effectiveness of these vaccines.


Assuntos
Lipossomos , Nanopartículas , Vacinas , Animais , Camundongos , RNA Mensageiro/química , Vacinas de mRNA , Transfecção , Células Apresentadoras de Antígenos , Nanopartículas/química
7.
Eur Eat Disord Rev ; 32(4): 718-730, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38459737

RESUMO

OBJECTIVE: This study examined the effect of cognitive bias modification for interpretation (CBM-I) training in Korean women with eating disorders (EDs). METHOD: Sixty-three women with EDs participated in the study. Participants were randomly assigned to the intervention group where they received six sessions of CBM-I training (n = 31) in addition to treatment-as-usual or were put on a waiting list (n = 32). Participants' interpretation and attention biases, emotion regulation, affect, and ED psychopathology were assessed at baseline, end-of-intervention (4 weeks), and follow-up (8 weeks). RESULTS: Participants who completed the CBM-I training displayed greater reductions in negative interpretation bias (Δη2 = 0.107) and emotion dysregulation (Δη2 = 0.085) with medium to large effect sizes compared to the control group, which were maintained from baseline to follow-up. Disengagement from negative faces and a focus on positive faces was found in the intervention group with a moderate effect size at the end-of-intervention (Δη2 = 0.090). Both intervention and control groups showed improvements in ED psychopathology. Baseline neuroticism was positively correlated with CBM-I effect. DISCUSSION: The results suggest that modifying interpretation bias towards ambiguous social stimuli might be an effective adjuvant treatment to reduce negative expectations of social situations and improve emotion regulation in women with bulimia nervosa and anorexia nervosa.


Assuntos
Terapia Cognitivo-Comportamental , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Feminino , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Adulto , Terapia Cognitivo-Comportamental/métodos , Distância Psicológica , Adulto Jovem , Viés de Atenção , Regulação Emocional , República da Coreia , Resultado do Tratamento
8.
J Virol ; 96(21): e0037122, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36286483

RESUMO

Gammaherpesviruses, including Epstein-Barr virus (EBV), are important human pathogens because they are associated with various tumors. Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional host nuclear protein responsible for poly(ADP-ribosyl)ation (PARylation) of target proteins. While PARP1 acts as a negative regulator that suppresses the lytic replication of gammaherpesviruses, viruses are often equipped with various strategies to overcome PARP1 inhibition. However, the mechanisms of how EBV may modulate a repressive host protein, PARP1, are still elusive. In this study, we found that EBV reactivation induced PARP1 downregulation in EBV-infected cells. EBV DNA polymerase processivity factor EA-D, encoded by the BMRF1 gene, directly interacted with the central automodification domain (AD) of PARP1 and was necessary and sufficient to downregulate PARP1 via K29-linked polyubiquitination. Moreover, knockdown of EA-D in B95.8 cells restored PARP1 levels and abrogated the expression of ZTA (also known as ZEBRA), a switch molecule of the EBV life cycle during reactivation. Interestingly, PARP1 PARylated RTA, another key switch molecule, and decreased RTA transactivation on the promoters of the ZTA, BMRF1, and BMLF1 genes. EA-D alleviated the PARylation of RTA and further enhanced RTA-mediated transactivation of these lytic promoters in reporter assays. Taken together, our results suggest that EBV viral processivity factor plays a key role in facilitating lytic replication by inducing PARP1 degradation via its interaction with the PARP1 AD, which is a highly conserved mechanism among gammaherpesviruses to counteract host repressive activity of PARP1 against viral lytic replication. IMPORTANCE PARP1 acts as a negative regulator of lytic replication in EBV. To successfully enter the reactivation cycle, EBV has developed multiple strategies to counteract the host's repressive mechanisms. In this study, we investigated how EBV manipulated the host repressive factor PARP1 to facilitate lytic replication. The EBV processivity factor EA-D downregulated PARP1 in a proteasome-dependent manner via its direct binding with PARP1 AD. The knockdown of EA-D restored the PARP1 level and inhibited ZTA expression during reactivation. Interestingly, PARP1 PARylated RTA and EA-D reduced the PARylation of RTA, thereby promoting the ZTA promoter activity. These results suggest that EA-D plays a key role in EBV lytic replication by inducing PARP1 degradation in addition to supporting DNA replication as a viral processivity factor. Given that the KSHV processivity factor also induces PARP1 degradation and enhances RTA function, gammaherpesviruses share a conserved molecular mechanism to overcome the inhibitory effects of PARP1, promoting lytic replication.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Humanos , Fator D do Complemento/genética , Infecções por Vírus Epstein-Barr/genética , Regulação Viral da Expressão Gênica , Herpesvirus Humano 4/genética , Regiões Promotoras Genéticas , Replicação Viral/genética , Poli(ADP-Ribose) Polimerases/metabolismo
9.
PLoS Pathog ; 17(1): e1009261, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33508027

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV), which belongs to the gammaherpesvirus subfamily, is associated with the pathogenesis of various tumors. Nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the polymerization of ADP-ribose units on target proteins. In KSHV-infected cells, PARP1 inhibits replication and transcription activator (RTA), a molecular switch that initiates lytic replication, through direct interaction. Thus, for efficient replication, KSHV has to overcome the molecular barrier in the form of PARP1. Previously, we have demonstrated that KSHV downregulates the expression of PARP1 through PF-8, a viral processivity factor. PF-8 induces ubiquitin-proteasome system-mediated degradation of PARP1 via direct physical association and enhances RTA transactivation activity. Here, we showed that dimerization domains of PF-8 are crucial not only for PARP1 interaction and degradation but also for enhancement of the RTA transactivation activity. PF-8 recruited CHFR for the PARP1 degradation. A knockdown of CHFR attenuated the PF-8-induced PARP1 degradation and enhancement of the RTA transactivation activity, leading to reduced KSHV lytic replication. These findings reveal a mechanism by which KSHV PF-8 recruits a cellular E3 ligase to curtail the inhibitory effect of PARP1 on KSHV lytic replication.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Herpesvirus Humano 8/genética , Proteínas Imediatamente Precoces/metabolismo , Proteínas de Neoplasias/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Transativadores/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Virais/metabolismo , Proteínas de Ciclo Celular/genética , Dimerização , Regulação para Baixo , Herpesvirus Humano 8/fisiologia , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas de Neoplasias/genética , Poli(ADP-Ribose) Polimerase-1/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Domínios Proteicos , Proteólise , Transativadores/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas Virais/genética , Replicação Viral
10.
Eur Radiol ; 33(11): 8270-8278, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37322163

RESUMO

OBJECTIVES: This study aimed to investigate whether performing [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in the prone position could reduce [18F]FDG uptake in dependent lungs. METHODS: Patients who underwent [18F]FDG PET/CT in both supine and prone positions from October 2018 to September 2021 were reviewed retrospectively. [18F]FDG uptake of dependent and nondependent lungs was analysed visually and semi-quantitatively. A linear regression analysis was performed to examine the association between the mean standardised uptake value (SUVmean) and the Hounsfield unit (HU). RESULTS: A total of 135 patients (median age, 66 years [interquartile range: 58-75 years]; 80 men) were included. Dependent lungs showed significantly higher SUVmean and HU than nondependent lungs on supine position PET/CT (sPET/CT, 0.59 ± 0.14 vs. 0.36 ± 0.09, p < 0.001; - 671 ± 66 vs. - 802 ± 43, p < 0.001, respectively) and prone position PET/CT (pPET/CT, 0.45 ± 0.12 vs. 0.42 ± 0.08, p < 0.001; - 731 ± 67 vs. - 790 ± 40, p < 0.001, respectively). Linear regression analysis revealed a strong association between the SUVmean and HU in sPET/CT (R = 0.86, p < 0.001) and moderate association in pPET/CT (R = 0.65, p < 0.001). One hundred and fifteen patients (85.2%) had visually discernible [18F]FDG uptake in the posterior lung on sPET/CT, which disappeared on pPET/CT in all but one patient (0.7%, p < 0.001). CONCLUSIONS: [18F]FDG uptake of the lung had moderate-to-strong associations with HU. Gravity-dependent opacity-related [18F]FDG uptake can be effectively reduced on prone position PET/CT. CLINICAL RELEVANCE STATEMENT: Prone position PET/CT effectively reduces gravity-dependent opacity-related [18F]fluorodeoxyglucose uptake in the lung, potentially improving diagnostic accuracy in evaluating nodules in dependent lungs and offering a more accurate assessment of lung inflammation parameters in interstitial lung disease evaluations. KEY POINTS: • The study evaluated whether performing [18F]fluorodeoxyglucose ([18F]FDG) PET/CT could reduce [18F]FDG uptake in lungs. • In prone and supine position PET/CT, the [18F]FDG uptake and Hounsfield unit were moderately to strongly associated. • Prone position PET/CT can reduce gravity-dependent opacity-related [18F]FDG uptake by the posterior lung.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Masculino , Humanos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Decúbito Ventral , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons/métodos
11.
Eur Radiol ; 33(10): 7340-7351, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37522898

RESUMO

OBJECTIVES: To investigate the predictability of synthetic relaxometry for neurodevelopmental outcomes in premature infants and to evaluate whether a combination of relaxation times with clinical variables or qualitative MRI abnormalities improves the predictive performance. METHODS: This retrospective study included 33 premature infants scanned with synthetic MRI near or at term equivalent age. Based on neurodevelopmental assessments at 18-24 months of corrected age, infants were classified into two groups (no/mild disability [n = 23] vs. moderate/severe disability [n = 10]). Clinical and MRI characteristics associated with moderate/severe disability were explored, and combined models incorporating independent predictors were established. Ultimately, the predictability of relaxation times, clinical variables, MRI findings, and a combination of the two were evaluated and compared. The models were internally validated using bootstrap resampling. RESULTS: Prolonged T1-frontal/parietal and T2-parietal periventricular white matter (PVWM), moderate-to-severe white matter abnormality, and bronchopulmonary dysplasia were significantly associated with moderate/severe disability. The overall predictive performance of each T1-frontal/-parietal PVWM model was comparable to that of individual MRI finding and clinical models (AUC = 0.71 and 0.76 vs. 0.73 vs. 0.83, respectively; p > 0.27). The combination of clinical variables and T1-parietal PVWM achieved an AUC of 0.94, sensitivity of 90%, and specificity of 91.3%, outperforming the clinical model alone (p = 0.049). The combination of MRI finding and T1-frontal PVWM yielded AUC of 0.86, marginally outperforming the MRI finding model (p = 0.09). Bootstrap resampling showed that the models were valid. CONCLUSIONS: It is feasible to predict adverse outcomes in premature infants by using early synthetic relaxometry. Combining relaxation time with clinical variables or MRI finding improved prediction. CLINICAL RELEVANCE STATEMENT: Synthetic relaxometry performed during the neonatal period may serve as a biomarker for predicting adverse neurodevelopmental outcomes in premature infants. KEY POINTS: • Synthetic relaxometry based on T1 relaxation time of parietal periventricular white matter showed acceptable performance in predicting adverse outcome with an AUC of 0.76 and an accuracy of 78.8%. • The combination of relaxation time with clinical variables and/or structural MRI abnormalities improved predictive performance of adverse outcomes. • Synthetic relaxometry performed during the neonatal period helps predict adverse neurodevelopmental outcome in premature infants.


Assuntos
Encéfalo , Recém-Nascido Prematuro , Recém-Nascido , Lactente , Humanos , Encéfalo/diagnóstico por imagem , Estudos Retrospectivos , Estudos de Viabilidade , Imageamento por Ressonância Magnética
12.
J Korean Med Sci ; 38(24): e191, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37337810

RESUMO

BACKGROUND: Korea's aging population has raised several challenges, especially concerning healthcare costs. Consequently, this study evaluated the association of frailty transitions with healthcare utilization and costs for older adults aged 70 to 84. METHODS: This study linked the frailty status data of the Korean Frailty and Aging Cohort Study to the National Health Insurance Database. We included 2,291 participants who had frailty measured by Fried Frailty phenotype at baseline in 2016-2017 and follow-up in 2018-2019. We conducted a multivariate regression analysis to determine the association between their healthcare utilization and costs by frailty transition groups. RESULTS: After 2 years, changes from "pre-frail" to "frail" (Group 6) and "frail" to "pre-frail" (Group 8) were significantly associated with increased inpatient days (P < 0.001), inpatient frequency (P < 0.001), inpatient cost (P < 0.001 and P < 0.01, respectively), and total healthcare cost (P < 0.001) than "robust" to "robust" (Group 1) older adults. A transition to frailty from "pre-frail" to "frail" (Group 6) resulted in a $2,339 total healthcare cost increase, and from "frail" to "pre-frail" (Group 8), a $1,605, compared to "robust" to "robust" older adults. CONCLUSION: Frailty among community-dwelling older adults is economically relevant. Therefore, it is crucial to study the burden of medical expenses and countermeasures for older adults to not only provide appropriate medical services but also to prevent the decline in their living standards due to medical expenses.


Assuntos
Fragilidade , Humanos , Idoso , Estudos de Coortes , Idoso Fragilizado , Aceitação pelo Paciente de Cuidados de Saúde , República da Coreia , Avaliação Geriátrica
13.
Genomics ; 114(4): 110432, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35843383

RESUMO

Soyasaponin is a type of glycoside such as steroids, steroidal alkaloids or triterpenes, which enhance the body immunity. In order to efficiently identify genes and markers related to the soyasaponin, we used a 180K Axiom® SoyaSNP array and whole genome resequencing data from the Korean soybean core collection. As a result of conducting GWAS for group A soyasaponin (Aa and Ab derivatives), 16 significant common markers associated with Aa and Ab derivatives were mapped to chromosome 7, and three candidate genes including Glyma.07g254600 were detected. The functional haplotypes for candidate genes showed that Aa and Ab contents were mainly determined by alleles of AX-90322128, the marker of Glyma.07g254600. In addition, 14 novel SNPs variants closely associated with Aa and Ab derivatives were discovered for Glyma.07g254600. Therefore, the results of this study that identified soyasaponin-associated markers and useful genes utilizing various genomic information could provide insight into functional soybean breeding.


Assuntos
Glycine max , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla/métodos , Melhoramento Vegetal , Locos de Características Quantitativas , Glycine max/genética
14.
Nano Lett ; 22(15): 6375-6382, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35877544

RESUMO

Spatiotemporal pH monitoring of single living cells across rigid cell and organelle membranes has been challenging, despite its significance in understanding cellular heterogeneity. Here, we developed a mechanically robust yet tolerably thin nanowire waveguide that enables in situ monitoring of pH dynamics at desired cellular compartments via direct optical communication. By chemically labeling fluorescein at one end of a poly(vinylbenzyl azide) nanowire, we continuously monitored pH variations of different compartments inside a living cell, successfully observing organelle-exclusive pH homeostasis and stimuli-selective pH regulations. Importantly, it was demonstrated for the first time that, during the mammalian cell cycle, the nucleus displays pH homeostasis in interphase but a tidal pH curve in the mitotic phase, implying the existence of independent pH-regulating activities by the nuclear envelope. The rapid and accurate local pH-reporting capability of our nanowire waveguide would be highly valuable for investigating cellular behaviors under diverse biological situations in living cells.


Assuntos
Nanofios , Animais , Núcleo Celular , Concentração de Íons de Hidrogênio , Mamíferos
15.
Int J Mol Sci ; 24(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37175665

RESUMO

Autoimmune neuroinflammatory diseases are a group of disorders resulting from abnormal immune responses in the nervous system, causing inflammation and tissue damage. The interleukin (IL) family of cytokines, especially IL-1, IL-6, and IL-17, plays a critical role in the pathogenesis of these diseases. IL-1 is involved in the activation of immune cells, production of pro-inflammatory cytokines, and promotion of blood-brain barrier breakdown. IL-6 is essential for the differentiation of T cells into Th17 cells and has been implicated in the initiation and progression of neuroinflammation. IL-17 is a potent pro-inflammatory cytokine produced by Th17 cells that plays a crucial role in recruiting immune cells to sites of inflammation. This review summarizes the current understanding of the roles of different interleukins in autoimmune neuroinflammatory diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, neuromyelitis optica, and autoimmune encephalitis, and discusses the potential of targeting ILs as a therapeutic strategy against these diseases. We also highlight the need for further research to better understand the roles of ILs in autoimmune neuroinflammatory diseases and to identify new targets for treating these debilitating diseases.


Assuntos
Doenças Autoimunes , Doenças Neuroinflamatórias , Humanos , Interleucina-17 , Interleucina-6 , Interleucinas , Inflamação/tratamento farmacológico , Citocinas , Células Th17 , Interleucina-1/uso terapêutico
16.
Int J Mol Sci ; 24(4)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36835486

RESUMO

Soybean seeds consist of approximately 40% protein and 20% oil, making them one of the world's most important cultivated legumes. However, the levels of these compounds are negatively correlated with each other and regulated by quantitative trait loci (QTL) that are controlled by several genes. In this study, a total of 190 F2 and 90 BC1F2 plants derived from a cross of Daepung (Glycine max) with GWS-1887 (G. soja, a source of high protein), were used for the QTL analysis of protein and oil content. In the F2:3 populations, the average protein and oil content was 45.52% and 11.59%, respectively. A QTL associated with protein levels was detected at Gm20_29512680 on chr. 20 with a likelihood of odds (LOD) of 9.57 and an R2 of 17.2%. A QTL associated with oil levels was also detected at Gm15_3621773 on chr. 15 (LOD: 5.80; R2: 12.2%). In the BC1F2:3 populations, the average protein and oil content was 44.25% and 12.14%, respectively. A QTL associated with both protein and oil content was detected at Gm20_27578013 on chr. 20 (LOD: 3.77 and 3.06; R2 15.8% and 10.7%, respectively). The crossover to the protein content of BC1F3:4 population was identified by SNP marker Gm20_32603292. Based on these results, two genes, Glyma.20g088000 (S-adenosyl-l-methionine-dependent methyltransferases) and Glyma.20g088400 (oxidoreductase, 2-oxoglutarate-Fe(II) oxygenase family protein), in which the amino acid sequence had changed and a stop codon was generated due to an InDel in the exon region, were identified.


Assuntos
Glycine max , Locos de Características Quantitativas , Glycine max/genética , Proteínas de Plantas/genética , Sementes/metabolismo , Glicina/metabolismo
17.
Psychooncology ; 31(3): 470-477, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34668264

RESUMO

OBJECTIVE: Patients with breast cancer receiving neoadjuvant chemotherapy are at increased risk of poor health-related quality of life (HRQOL). This study examined clinical caseness on depression and anxiety mediate the relationship between resilience and HRQOL in patients with breast cancer. METHODS: A total of 193 patients with breast cancer undergoing neoadjuvant chemotherapy completed questionnaires including the Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy-Breast before the first session (T0), before the start of the last session (T1), and 6 months after the end (T2) of chemotherapy. Mediation analyses using a bootstrapping method was performed. RESULTS: The indirect effect (IE) through T1 depression was significant (IE through depression = 0.043, 95% confidence interval [CI] [0.002-0.090]), while IE through T1 anxiety was not significant (IE through anxiety = 0.037, 95% CI [-0.010-0.097]) in the association between T0 resilience and T2 HRQOL. CONCLUSIONS: Clinical caseness on HADS depression subscale during chemotherapy was a mediating factor of the relationship between resilience before chemotherapy and HRQOL after chemotherapy in patients with breast cancer receiving neoadjuvant chemotherapy. Depression during chemotherapy in patients with breast cancer may be a target symptom of screening and intervention to maintain the HRQOL after chemotherapy. Also, patients with low resilience are more likely to develop depression during chemotherapy, and clinicians should carefully monitor whether depression occurs in these patients with low resilience.


Assuntos
Neoplasias da Mama , Qualidade de Vida , Ansiedade/psicologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Depressão/psicologia , Feminino , Humanos , Qualidade de Vida/psicologia , Inquéritos e Questionários
18.
Neuroradiology ; 64(2): 381-392, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34382095

RESUMO

PURPOSE: To validate the use of synthetic magnetic resonance imaging (SyMRI) volumetry by comparing with child-optimized SPM 12 volumetry in 3 T pediatric neuroimaging. METHODS: In total, 106 children aged 4.7-18.7 years who underwent both synthetic and 3D T1-weighted imaging and had no abnormal imaging/neurologic findings were included for the SyMRI vs. SPM T1-only segmentation (SPM T1). Forty of the 106 children who underwent an additional 3D T2-weighted imaging were included for the SyMRI vs. SPM multispectral segmentation (SPM multi). SPM segmentation using an age-appropriate atlas and inverse-transforming template-space intracranial mask was compared with SyMRI segmentation. Volume differences between SyMRI and SPM T1 were plotted against age to evaluate the influence of age on volume difference. RESULTS: Measurements derived from SyMRI and two SPM methods showed excellent agreements and strong correlations except for the CSF volume (CSFV) (intraclass correlation coefficients = 0.87-0.98; r = 0.78-0.96; relative volume difference other than CSFV = 6.8-18.5% [SyMRI vs. SPM T1] and 11.3-22.7% [SyMRI vs. SPM multi]). Dice coefficients of all brain tissues (except CSF) were in the range 0.78-0.91. The Bland-Altman plot and age-related volume difference change suggested that the volume differences between the two methods were influenced by the volume of each brain tissue and subject's age (p < 0.05). CONCLUSION: SyMRI and SPM segmentation results were consistent except for CSFV, which supports routine clinical use of SyMRI-based volumetry in pediatric neuroimaging. However, caution should be taken in the interpretation of the CSF segmentation results.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Criança , Humanos , Imageamento Tridimensional , Neuroimagem
19.
J Chem Ecol ; 48(2): 207-218, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35006526

RESUMO

The bean bug, Riptortus pedestris, is a polyphagous insect that feeds primarily on leguminous plants, especially soybean (Glycine max). Although the bean bug is an economically important pest of soybean, little is known about how the insect locates soybean fields. In this study, we examined the electroantennogram responses of R. pedestris to soybean volatiles and examined the behavioral responses of the adult bean bugs. R. pedestris adults were attracted more to their host-plant soybean, even when physical contact was absent, than to air or a non-host plant. Accordingly, we hypothesized that R. pedestris can recognize soybean through a plant's volatile organic compounds (VOCs). Five VOCs were identified from intact soybean plants at the vegetative stage: (Z)-3-hexen-1-ol, (Z)-3-hexenyl acetate, 4-ethylbenzaldehyde, α-farnesene, and methyl salicylate. Response spectra of the antennae to these volatiles clearly showed that both male and female R. pedestris can detect soybean volatiles. The adult bean bugs did not show behavioral orientation to any individual compounds but showed significant orientation to a particular blend of synthetic soybean volatiles when tested under laboratory conditions. In the field, this soybean volatile blend did not significantly attract the bean bugs, but it did interact synergistically with the aggregation pheromone to attract the bean bugs. These results highlight the role of host plant volatiles in the sensory ecology of R. pedestris and help explain colonization pattern of the bean bugs in soybean fields.


Assuntos
Fabaceae , Heterópteros , Compostos Orgânicos Voláteis , Animais , Heterópteros/fisiologia , Feromônios , Glycine max , Compostos Orgânicos Voláteis/farmacologia
20.
Exp Cell Res ; 407(2): 112815, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34496296

RESUMO

Although the incidence rates of head and neck squamous cell carcinoma (HNSCC) associated with human papilloma virus (HPV) infection have recently been on the rise, the underlying mechanism of its tumorigenesis remains largely unknown. Here, we investigated whether HNSCC cells with high expression of integrin alpha 6 (ITGα6), one of the HPV receptors, have a preference during HPV infection. In addition, we examined the gain or loss of function of the ITGα6 gene in HPV + ve HNSCC cells, as well as its prognostic value in patients with HNSCC. HPV pseudovirus was found to be more infective, with HNSCC cells featuring an overexpressed ITGα6 gene compared to the control cells. Overexpression and suppression of ITGα6 respectively increases and decreases stemness phenotypes of HPV + ve HNSCC cells. Furthermore, ITGα6 can regulate stemness by partially mediating AKT pathway in HPV + ve HNSCC cells. Finally, patients with HPV + ve HNSCC had a poor prognosis in cases of elevated ITGα6 expression; however, the expression levels of ITGα6 did not influence the survival rates of HPV-negative HNSCC patients. In conclusion, ITGα6 can serve as a potential therapeutic target for HPV + ve HNSCC cancer-like stem cells (CSCs).


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/patologia , Integrina alfa6/metabolismo , Células-Tronco Neoplásicas/patologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Integrina alfa6/genética , Camundongos , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/virologia , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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