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1.
J Res Adolesc ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717122

RESUMO

In past decades, the positive role of self-control in students' academic success has attracted plenty of scholarly attention. However, fewer studies have examined the link between adolescents' neural development of the inhibitory control system and their academic achievement, especially using a longitudinal approach. Moreover, less is known about the role of parents in this link. Using large-scale longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study (N = 9574; mean age = 9.94 years at baseline, SD = .63; 50% girls), the current study took an integrative biopsychosocial approach to explore the longitudinal link between early adolescents' fronto-striatal connectivity and their academic achievement, with attention to the moderating role of parental warmth. Results showed that weaker intrinsic connectivity between the frontoparietal network and the striatum was associated with early adolescents' worse academic achievement over 2 years during early adolescence. Notably, parental warmth moderated the association between fronto-striatal connectivity and academic achievement, such that weaker fronto-striatal connectivity was only predictive of worse academic achievement among early adolescents who experienced low levels of parental warmth. Taken together, the findings demonstrate weaker fronto-striatal connectivity as a risk factor for early adolescents' academic development and highlight parental warmth as a protective factor for academic development among those with weaker connectivity within the inhibitory control system.

2.
J Fam Psychol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635176

RESUMO

Greater neural similarity between parents and adolescents may reduce adolescent substance use. Among 70 parent-adolescent dyads, we tested a longitudinal path model in which family economic environment is related to adolescent substance use, directly and indirectly through parent-adolescent neural similarity and parental monitoring. Neural similarity was measured as parent-adolescent pattern similarity in functional brain connectivity at Time 1. Parents reported socioeconomic status and parental monitoring at Time 1. Adolescents reported parental monitoring at Time 1 and substance use at Time 2. Higher family socioeconomic status was associated with greater neural similarity. Greater neural similarity was associated with lower adolescent substance use, mediated through greater adolescent-perceived parental monitoring. Parent-adolescent neural similarity may attenuate adolescent substance use by bolstering parental monitoring. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

3.
Int J Mol Sci ; 25(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38612446

RESUMO

Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.


Assuntos
Camellia sinensis , Catequina , Humanos , Metabolismo Secundário , Éxons , Cromossomos Humanos Par 15 , Camellia sinensis/genética , Chá
4.
BMC Sports Sci Med Rehabil ; 16(1): 51, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38378630

RESUMO

BACKGROUND: Cardiac rehabilitation (CR) is recommended for patients with cardiovascular disease. However, the participation and completion rates for hospital-based CR are low, and home-based CR has been suggested as an alternative. This study aimed to develop a home-based CR program and assess the feasibility of the program over a 6-week period in patients with left ventricular dysfunction or a history of myocardial infarction. METHODS: This feasibility study consisted of two phases. The initial phase (Study 1) focused on developing the home-based exercise protocol. Systematic approaches to developing evidence-based home-based exercise intervention were implemented including systematic review, patient surveys, and expert consensus. Study 2 aimed to evaluate the feasibility of a 6-week home-based CR program that was based on the results of Study 1. Study 2 included two exercise education sessions and four telephone counseling sessions. During this stage of the exercise program, the participants exercised on two separate days and their experiences while performing the aerobic and resistance exercises were surveyed. Eight participants participated in Study 1 and 16 participated in Study 2. RESULTS: Participants expressed overall satisfaction with the exercise program in Study 1. Heart rate increased in response to exercise, but this did not correspond with perceived exertion. The aim of the home-based CR exercise program was for participants to achieve exercise goals (≥150 min/week of aerobic type exercises as well as at least twice weekly resistance exercise using own body weights). We aimed to increase compliance and adherence to the home-based CR program. In Study 2, 13 out of 16 participants (81.3%) completed the 6-week home-based CR program, with a participation rate of 100% in both exercise education and phone counseling sessions. Adherence to the home-based exercise protocol was 83.1% and no serious adverse events were observed. At the beginning of the study, only three out of 13 participants (23.1%) met the requirements for both aerobic and resistance exercises, but at the end of the 6-week program, 10 out of 13 participants (76.9%) fulfilled the requirements. CONCLUSION: The exercise program developed in this study was safe and feasible, and the 6-week home-based CR program was feasible for patients with cardiovascular disease without any reported adverse effects.

5.
Data Brief ; 53: 110140, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38357452

RESUMO

The current dataset aims to support and enhance the research reliability of neuromelanin regions in the brainstem, such as locus coeruleus (LC), by offering raw neuromelanin-sensitive images. The dataset includes raw neuromelanin-sensitive images from 157 healthy individuals (8-64 years old). In addition, leveraging individual neuromelanin-sensitive images, a non-linear neuromelanin-sensitive atlas, generated through an iterative warping process, is included to tackle the common challenge of a limited field of view in neuromelanin-sensitive images. Finally, the dataset encompasses a probabilistic LC atlas generated through a majority voting approach with pre-existing multiple atlas-based segmentations. This process entails warping pre-existing atlases onto individual spaces and identifying voxels with a majority consensus of over 50 % across the atlases. This LC probabilistic atlas can minimize uncertainty variance associated with choosing a specific single atlas.

6.
Transl Neurodegener ; 13(1): 4, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195518

RESUMO

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly and represents a major clinical challenge in the ageing society. Neuropathological hallmarks of AD include neurofibrillary tangles composed of hyperphosphorylated tau, senile plaques derived from the deposition of amyloid-ß (Aß) peptides, brain atrophy induced by neuronal loss, and synaptic dysfunctions. Death-associated protein kinase 1 (DAPK1) is ubiquitously expressed in the central nervous system. Dysregulation of DAPK1 has been shown to contribute to various neurological diseases including AD, ischemic stroke and Parkinson's disease (PD). We have established an upstream effect of DAPK1 on Aß and tau pathologies and neuronal apoptosis through kinase-mediated protein phosphorylation, supporting a causal role of DAPK1 in the pathophysiology of AD. In this review, we summarize current knowledge about how DAPK1 is involved in various AD pathological changes including tau hyperphosphorylation, Aß deposition, neuronal cell death and synaptic degeneration. The underlying molecular mechanisms of DAPK1 dysregulation in AD are discussed. We also review the recent progress regarding the development of novel DAPK1 modulators and their potential applications in AD intervention. These findings substantiate DAPK1 as a novel therapeutic target for the development of multifunctional disease-modifying treatments for AD and other neurological disorders.


Assuntos
Doença de Alzheimer , Idoso , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Proteínas Quinases Associadas com Morte Celular/genética , Peptídeos beta-Amiloides , Sistema Nervoso Central , Emaranhados Neurofibrilares
7.
J Breath Res ; 18(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38176080

RESUMO

When attempts to lose body fat mass frequently fail, breath acetone (BA) monitoring may assist fat mass loss during a low-carbohydrate diet as it can provide real-time body fat oxidation levels. This randomized controlled study aimed to evaluate the effectiveness of monitoring BA levels and providing feedback on fat oxidation during a three-week low-carbohydrate diet intervention. Forty-seven participants (mean age = 27.8 ± 4.4 years, 53.3% females, body mass index = 24.1 ± 3.4 kg m-2) were randomly assigned to three groups (1:1:1 ratio): daily BA assessment with a low-carbohydrate diet, body weight assessment (body scale (BS)) with a low-carbohydrate diet, and low-carbohydrate diet only. Primary outcome was the change in fat mass and secondary outcomes were the changes in body weight and body composition. Forty-five participants completed the study (compliance rate: 95.7%). Fat mass was significantly reduced in all three groups (allP< 0.05); however, the greatest reduction in fat mass was observed in the BA group compared to the BS (differences in changes in fat mass, -1.1 kg; 95% confidence interval: -2.3, -0.2;P= 0.040) and control (differences in changes in fat mass, -1.3 kg; 95% confidence interval: -2.1, -0.4;P= 0.013) groups. The BA group showed significantly greater reductions in body weight and visceral fat mass than the BS and control groups (allP< 0.05). In addition, the percent body fat and skeletal muscle mass were significantly reduced in both BA and BS groups (allP< 0.05). However, no significant differences were found in changes in body fat percentage and skeletal muscle mass between the study groups. Monitoring BA levels, which could have motivated participants to adhere more closely to the low-carbohydrate diet, to assess body fat oxidation rates may be an effective intervention for reducing body fat mass (compared to body weight assessment or control conditions). This approach could be beneficial for individuals seeking to manage body fat and prevent obesity.


Assuntos
Acetona , Redução de Peso , Feminino , Humanos , Adulto Jovem , Adulto , Masculino , Testes Respiratórios , Composição Corporal/fisiologia , Peso Corporal , Tecido Adiposo
8.
Investig Clin Urol ; 65(1): 77-83, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38197754

RESUMO

PURPOSE: Infertility affects 10% to 15% of couples, and male factor accounts for 50% of the cases. The relevant male genetic factors, which account for at least 15% of male infertility, include Y-chromosome microdeletions. We investigated clinical data and patterns of Y-chromosome microdeletions in Korean infertile men. MATERIALS AND METHODS: A total of 919 infertile men whose sperm concentration was ≤5 million/mL in two consecutive analyses were investigated for Y-chromosome microdeletion. Among them, 130 infertile men (14.1%) demonstrated Y-chromosome microdeletions. Medical records were retrospectively reviewed. RESULTS: In 130 men with Y-chromosome microdeletions, 90 (69.2%) had azoospermia and 40 (30.8%) had severe oligozoospermia. The most frequent microdeletions were in the azoospermia factor (AZF) c region (77/130, 59.2%), followed by the AZFb+c (30/130, 23.1%), AZFa (8/130, 6.2%), AZFb (7/130, 5.4%), AZFa+b+c (7/130, 5.4%), and AZFa+c (1/130, 0.7%) regions. In men with oligozoospermia, 37 (92.5%) had AZFc microdeletion. Chromosomal abnormalities were detected in 30 patients (23.1%). Higher follicle-stimulating hormone level (23.2±13.5 IU/L vs. 15.1±9.0 IU/L, p<0.001), higher luteinizing hormone level (9.7±4.6 IU/L vs. 6.0±2.2 IU/L, p<0.001), and lower testis volume (10.6±4.8 mL vs. 13.3±3.8 mL, p<0.001) were observed in azoospermia patients compared to severe oligozoospermia patients. CONCLUSIONS: Y-chromosome microdeletion is a common genetic cause of male infertility. Therefore, Y-chromosome microdeletion test is recommended for the accurate diagnosis of men with azoospermia or severe oligozoospermia. Appropriate genetic counseling is mandatory before the use of assisted reproduction technique in men with Y-chromosome microdeletion.


Assuntos
Azoospermia , Infertilidade Masculina , Oligospermia , Masculino , Humanos , Azoospermia/genética , Oligospermia/genética , Estudos Retrospectivos , Sêmen , Infertilidade Masculina/genética , República da Coreia
9.
Sci Rep ; 14(1): 2622, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38297008

RESUMO

Although increase in physical activity is important to improve prognosis of cardiac patients in addition to hospital-based exercise cardiac rehabilitation, their physical activity levels are not properly understood. This study aimed to examine domain- and intensity-specific physical activity in individuals with coronary heart disease (CHD) and compare them with non-CHD individuals. Data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2019 were analyzed, including 1083 CHD patients and 38,532 non-CHD individuals. The inclusion criteria were age 19 years or older and data not missing for CHD information. Before and after propensity score matching (PSM) for age, sex, body mass index, education, household income, alcohol intake, and smoking status, domain (leisure, work, transportation)-and intensity (moderate, vigorous) -specific physical activity participation levels were compared between individuals with and without CHD. Before PSM, CHD individuals were older, less educated, more sedentary, and participated less in PAs compared to non-CHD individuals. After PSM, CHD individuals had similar levels of domain-specific PAs. However, they had higher work-related PA levels (29.7 ± 209.6 vs. 42.1 ± 291.3 min/week p = 0.022) and more sedentary time (487.2 ± 224.2 vs. 514.1 ± 228.7. p = 0.003) than those without CHD. Subgroup analysis revealed lower leisure-related PA in men with CHD (63.5 ± 165.5 vs. 47.3 ± 140.2, p < 0.05) and higher work-related PA in women with CHD (18.9 ± 159.7 vs. 57.1 ± 397.5, p < 0.01). Among those < 65 years of age, individuals with CHD spent more time sedentary than individuals without CHD. CHD individuals are not physically inactive compared with non-CHD individuals who are similar in sociodemographic status and lifestyle. CHD patients' PA levels may have been underestimated.


Assuntos
Reabilitação Cardíaca , Doença das Coronárias , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Inquéritos Nutricionais , Inquéritos e Questionários , Exercício Físico , Doença das Coronárias/epidemiologia
10.
Mol Neurobiol ; 61(3): 1794-1806, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37775722

RESUMO

Death-associated protein kinase 1 (DAPK1) is a stress-responsive calcium/calmodulin (CaM)-regulated serine/threonine protein kinase that is actively involved in stress-induced cell death. The dysregulation of DAPK1 has been established in various neurological disorders such as epilepsy, Alzheimer's disease (AD), and Parkinson's disease (PD). Recent research indicates a synaptic localization of DAPK1 in neurons, suggesting a potential role of DAPK1 in modulating synaptic structure and function. However, the key molecules and pathways underlying the influence of DAPK1 on synapses remain elusive. We utilized quantitative proteomic and phosphoproteomic analyses to compare the differences in protein expression and phosphorylation in hippocampal tissues of wild-type (WT) and DAPK1-knockout (KO) mice. Bioinformatic analysis of differentially expressed proteins and phosphoproteins revealed a preferential enrichment of proteins involved in regulating synaptic function, cytoskeletal structure, and neurotransmission. Gene set enrichment analysis (GESA) highlighted altered presynaptic functions including synaptic vesicle priming and glutamate secretion in KO mice. Besides, we observed that proteins with potential phosphorylation motifs of ERK and DAPK1 were overrepresented among the differential phosphoproteins and were highly enriched in neuronal function-related pathways. Furthermore, Western blot analysis validated differences in the expression of several proteins closely associated with presynaptic organization, dendrites and calcium transmembrane transport between KO and WT mice, further corroborating the potential involvement of DAPK1 in the regulation of synaptic functions. Overall, our data provide molecular evidence to elucidate the physiological links between DAPK1 and neuronal functions and help clarify the role of DAPK1 in the pathogenesis of neurodevelopmental and neurodegenerative diseases.


Assuntos
Cálcio , Proteômica , Animais , Camundongos , Proteínas Quinases Associadas com Morte Celular/metabolismo , Hipocampo/metabolismo , Camundongos Knockout , Fosfoproteínas/metabolismo , Sinapses/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-37121398

RESUMO

BACKGROUND: Socioecological factors such as family environment and parenting behaviors contribute to the development of substance use. While biobehavioral synchrony has been suggested as the foundation for resilience that can modulate environmental effects on development, the role of brain similarity that attenuates deleterious effects of environmental contexts has not been clearly understood. We tested whether parent-adolescent neural similarity-the level of pattern similarity between parent-adolescent functional brain connectivity representing the level of attunement within each dyad-moderates the longitudinal pathways in which household chaos (a stressor) predicts adolescent substance use directly and indirectly via parental monitoring. METHODS: In a sample of 70 parent-adolescent dyads, similarity in resting-state brain activity was identified using multipattern connectivity similarity estimation. Adolescents and parents reported on household chaos and parental monitoring, and adolescent substance use was assessed at a 1-year follow-up. RESULTS: The moderated mediation model indicated that for adolescents with low neural similarity, but not high neural similarity, greater household chaos predicted higher substance use over time directly and indirectly via lower parental monitoring. Our data also indicated differential susceptibility in the overall association between household chaos and substance use: Adolescents with low neural similarity exhibited high substance use under high household chaos but low substance use under low household chaos. CONCLUSIONS: Neural similarity acts as a protective factor such that the detrimental effects of suboptimal family environment and parenting behaviors on the development of adolescent health risk behaviors may be attenuated by neural similarity within parent-adolescent bonds.


Assuntos
Poder Familiar , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Fatores de Proteção , Características da Família , Encéfalo
12.
CNS Neurosci Ther ; 30(3): e14432, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37641913

RESUMO

AIMS: The autophagy-lysosomal pathway is important for maintaining cellular proteostasis, while dysfunction of this pathway has been suggested to drive the aberrant intraneuronal accumulation of tau protein, leading to synaptic damage and cognitive impairment. Previous studies have demonstrated that the activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin has a positive impact on cognition and AD-related biomarkers. However, the effect and mechanism of TPRV1 activation on neuronal tau homeostasis remain elusive. METHODS: A mouse model of tauopathy was established by overexpressing full-length human tau in the CA3 area. Mice were fed capsaicin diet (0.0125%) or normal diet for 9 weeks. The cognitive ability, synaptic function, tau phosphorylation levels, and autophagy markers were detected. In vitro, capsaicin-induced alterations in cellular autophagy and tau degradation were characterized using two cell models. Besides, various inhibitors were applied to validate the role of TRPV1-mediated autophagy enhancement in tau clearance. RESULTS: We observed that TRPV1 activation by capsaicin effectively mitigates hippocampal tau accumulation-induced synaptic damages, gliosis, and cognitive impairment in vivo. Capsaicin promotes the degradation of abnormally accumulated tau through enhancing autophagic function in neurons, which is dependent on TRPV1-mediated activation of AMP-activated protein kinase (AMPK) and subsequent inhibition of the mammalian target of rapamycin (mTOR). Blocking AMPK activation abolishes capsaicin-induced autophagy enhancement and tau degradation in neurons. CONCLUSION: Our findings reveal that capsaicin-induced TRPV1 activation confers neuroprotection by restoring neuronal tau homeostasis via modulating cellular autophagy and provides additional evidence to support the potential of TRPV1 as a therapeutic target for tauopathies.


Assuntos
Antineoplásicos , Disfunção Cognitiva , Animais , Humanos , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Capsaicina/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Mamíferos/metabolismo , Proteínas tau/metabolismo , Canais de Cátion TRPV/metabolismo
13.
Subst Use Misuse ; 59(1): 79-89, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37936270

RESUMO

BACKGROUND AND OBJECTIVES: Use of psychotropic substances in childhood has been associated with both impulsivity and other manifestations of poor executive function as well as escalation over time to use of progressively stronger substances. However, how this relationship may start in earlier childhood has not been well explored. Here, we investigated the neurobehavioral correlates of daily caffeinated soda consumption in preadolescent children and examined whether caffeinated soda intake is associated with a higher risk of subsequent alcohol initiation. METHODS: Using Adolescent Brain Cognitive Development study data (N = 2,092), we first investigated cross-sectional relationships between frequent caffeinated soda intake and well-known risk factors of substance misuse: impaired working memory, high impulsivity, and aberrant reward processing. We then examined whether caffeinated soda intake at baseline predicts more alcohol sipping at 12 months follow-up using a machine learning algorithm. RESULTS: Daily consumption of caffeinated soda was cross-sectionally associated with neurobehavioral risk factors for substance misuse such as higher impulsivity scores and lower working memory performance. Furthermore, caffeinated soda intake predicted a 2.04 times greater likelihood of alcohol sipping after 12 months, even after controlling for rates of baseline alcohol sipping rates. CONCLUSIONS: These findings suggest that previous linkages between caffeine and substance use in adolescence also extend to younger initiation, and may stem from core neurocognitive features thought conducive to substance initiation.


Assuntos
Bebidas , Bebidas Gaseificadas , Adolescente , Humanos , Criança , Bebidas/efeitos adversos , Cafeína , Fatores de Risco
14.
Int J Mol Sci ; 24(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38003448

RESUMO

Alzheimer's disease (AD) is a complex multifactorial disorder that poses a substantial burden on patients, caregivers, and society. Considering the increased aging population and life expectancy, the incidence of AD will continue to rise in the following decades. However, the molecular pathogenesis of AD remains controversial, superior blood-based biomarker candidates for early diagnosis are still lacking, and effective therapeutics to halt or slow disease progression are urgently needed. As powerful genetic regulators, microRNAs (miRNAs) are receiving increasing attention due to their implications in the initiation, development, and theranostics of various diseases, including AD. In this review, we summarize miRNAs that directly target microtubule-associated protein tau (MAPT), amyloid precursor protein (APP), and ß-site APP-cleaving enzyme 1 (BACE1) transcripts and regulate the alternative splicing of tau and APP. We also discuss related kinases, such as glycogen synthase kinase (GSK)-3ß, cyclin-dependent kinase 5 (CDK5), and death-associated protein kinase 1 (DAPK1), as well as apolipoprotein E, that are directly targeted by miRNAs to control tau phosphorylation and amyloidogenic APP processing leading to Aß pathologies. Moreover, there is evidence of miRNA-mediated modulation of inflammation. Furthermore, circulating miRNAs in the serum or plasma of AD patients as noninvasive biomarkers with diagnostic potential are reviewed. In addition, miRNA-based therapeutics optimized with nanocarriers or exosomes as potential options for AD treatment are discussed.


Assuntos
Doença de Alzheimer , MicroRNAs , Humanos , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Secretases da Proteína Precursora do Amiloide/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo , Fosforilação , Peptídeos beta-Amiloides/metabolismo
15.
Arch Pharm Res ; 46(11-12): 882-896, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37804415

RESUMO

Breast cancer is one of the major malignancies in women, and most related deaths are due to recurrence, drug resistance, and metastasis. The expression of the mouse double minute 2 (MDM2) oncogene is upregulated in breast cancer; however, its regulatory mechanism has yet to be fully elucidated. Herein, we identified the tumor suppressor death-associated protein kinase 1 (DAPK1) as a novel MDM2 regulator by unbiased peptide library screening. DAPK1 is directly bound to MDM2 and phosphorylates it at Thr419. DAPK1-mediated MDM2 phosphorylation promoted its protein degradation via the ubiquitin-proteasome pathway, resulting in upregulated p53 expression. DAPK1 overexpression, but not its kinase activity-deficient form, decreased colony formation and increased doxorubicin-induced cell death; however, DAPK1 knockdown produced the opposite effects in human breast cancer cells. In a xenograft tumorigenesis assay, DAPK1 overexpression significantly reduced tumor formation, whereas inhibition of DAPK1 kinase activity reduced its antitumorigenic effect. Finally, DAPK1 expression was negatively correlated with MDM2 levels in human breast cancer tissues. Thus, these results suggest that DAPK1-mediated MDM2 phosphorylation and its protein degradation may contribute to its antitumorigenic function in breast cancer.


Assuntos
Neoplasias da Mama , Proteína Supressora de Tumor p53 , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proteínas Quinases Associadas com Morte Celular/metabolismo , Fosforilação , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo
16.
Food Sci Anim Resour ; 43(5): 914-937, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37701750

RESUMO

The objective of this study was to establish a multi-residue quantitative method for the analysis of anthelmintic and antiprotozoal drugs in various livestock products (beef, pork, and chicken) using ultra-high-performance liquid chromatography-tandem mass spectrometry. Each compound performed validation at three different levels i.e., 0.5, 1, and 2× the maximum residue limit according to the CODEX guidelines (CAC/GL 71-2009). This study was conducted according to the modified quick, easy, cheap, effective, rugged, and safe procedure. The matrix-matched calibrations gave correlation coefficients >0.98, and the obtained recoveries were in the range of 60.2%-119.9%, with coefficients of variation ≤32.0%. Furthermore, the detection and quantification limits of the method were in the ranges of 0.03-3.2 and 0.1-9.7 µg/kg, respectively. Moreover, a survey of residual anthelmintic and antiprotozoal drugs was also carried out in 30 samples of beef, pork, and chicken collected in Korea. Toltrazuril sulfone was detected in all three samples. Thus, our results indicated that the developed method is suitable for determining the anthelmintic and antiprotozoal drug contents in livestock products.

17.
Investig Clin Urol ; 64(5): 489-494, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37668205

RESUMO

PURPOSE: We compared semen quality and sperm DNA fragmentation in cancer patients who underwent sperm banking and controls who underwent sperm cryopreservation for assisted reproductive technology (ART). MATERIALS AND METHODS: A total of 132 men, 65 cancer patients and 67 controls, were prospectively enrolled and performed sperm cryopreservation for fertility preservation from May 2019 to February 2021. Sperm quality was determined by measuring semen volume, sperm concentration, sperm motility, and sperm DNA fragmentation index (DFI). Sperm quality and sperm DFI were compared in cancer patients and controls. RESULTS: The major cancers of the 65 cancer patients were leukemia (26.2%), testicular cancer (23.1%), and lymphoma (20.0%). Sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls. Sperm DFI was significantly higher in cancer patients than in controls (24.32%±15.69% vs. 19.11%±11.63%; p=0.033). After excluding 8 cancer patients who received chemotherapy before sperm banking, sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls, but there was no significant difference in sperm DFI for cancer patients and controls (23.14%±12.79% vs. 19.11%±11.63%; p=0.069). CONCLUSIONS: Sperm quality was lower in cancer patients than in controls. There was no difference in the sperm DFI of cancer patients prior to chemotherapy and men presenting for sperm cryopreservation for ART. We recommend that all men who are planning cancer therapy should be offered sperm banking prior to gonadotoxic chemotherapy as a standard of fertility preservation.


Assuntos
Análise do Sêmen , Neoplasias Testiculares , Humanos , Masculino , Motilidade dos Espermatozoides , Fragmentação do DNA , Sêmen , Criopreservação , Espermatozoides
18.
J Cogn Neurosci ; 35(10): 1557-1569, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37584586

RESUMO

The locus coeruleus (LC) is a brainstem region associated with broad neural arousal because of norepinephrine production, but it has increasingly been associated with specific cognitive processes. These include sustained attention, with deficits associated with various neuropsychological disorders. Neural models of attention deficits have focused on interrupted dynamics between the salience network (SAL) with the frontoparietal network, which has been associated with task-switching and processing of external stimuli, respectively. Conflicting findings for these regions suggest the possibility of upstream signaling leading to attention dysfunction, and recent research suggests LC involvement. In this study, resting-state functional connectivity and behavioral performance on an attention task was examined within 584 individuals. Analysis revealed significant clusters connected to LC activity in the SAL. Given previous findings that attention deficits may be caused by SAL network switching dysfunctions, findings here further suggest that dysfunction in LC-SAL connectivity may impair attention.


Assuntos
Locus Cerúleo , Imageamento por Ressonância Magnética , Humanos , Locus Cerúleo/diagnóstico por imagem , Tronco Encefálico , Vias Neurais/diagnóstico por imagem , Nível de Alerta
19.
Biomed Pharmacother ; 166: 115383, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37643483

RESUMO

The functional complexity of the central nervous system (CNS) is unparalleled in living organisms. It arises from neural crest-derived cells that migrate by the exact route, leading to the formation of a complex network of neurons and glial cells. Recent studies have shown that novel crosstalk exists between the Notch1 and Nrf2 pathways and is associated with many neurological diseases. The Notch1-Nrf2 axis may act on nervous system development, and the molecular mechanism has recently been reported. In this review, we summarize the essential structure and function of the CNS. The significance of interactions between signaling pathways and between developmental processes like proliferation, apoptosis and migration in ensuring the correct development of the CNS is also presented. We primarily focus on research concerning possible mechanism of interaction between Notch1 and Nrf2 and the functions of Notch1-Nrf2 in neurons. There may be a direct interaction between Notch1 and NRF2, which is closely related to the crosstalk that occurs between them. The significance and potential applications of the Notch1-Nrf2 axis in abnormal development of the nervous system are been highlighten. We also discuss the molecular mechanisms by which the Notch1-Nrf2 axis controls the apoptosis, antioxidant pathway and differentiation of neurons to modulate the development of the nervous system. This information will lead to a better understanding of Notch1-Nrf2 axis signaling pathways in the nervous system and may facilitate the development of new therapeutic strategies.


Assuntos
Sistema Nervoso Central , Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Neuroglia , Neurônios
20.
J Neurosci ; 43(33): 5936-5943, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37400252

RESUMO

Despite a recent surge in research examining parent-child neural similarity using fMRI, there remains a need for further investigation into how such similarity may play a role in children's emotional adjustment. Moreover, no prior studies explored the potential contextual factors that may moderate the link between parent-child neural similarity and children's developmental outcomes. In this study, 32 parent-youth dyads (parents: M age = 43.53 years, 72% female; children: M age = 11.69 years, 41% female) watched an emotion-evoking animated film while being scanned using fMRI. We first quantified how similarly emotion network interacts with other brain regions in responding to the emotion-evoking film between parents and their children. We then examined how such parent-child neural similarity is associated with children's emotional adjustment, with attention to the moderating role of family cohesion. Results revealed that higher parent-child similarity in functional connectivity pattern during movie viewing was associated with better emotional adjustment, including less negative affect, lower anxiety, and greater ego resilience in youth. Moreover, such associations were significant only among families with higher cohesion, but not among families with lower cohesion. The findings advance our understanding of the neural mechanisms underlying how children thrive by being in sync and attuned with their parents, and provide novel empirical evidence that the effects of parent-child concordance at the neural level on children's development are contextually dependent.SIGNIFICANCE STATEMENT What neural processes underlie the attunement between children and their parents that helps children thrive? Using a naturalistic movie-watching fMRI paradigm, we find that greater parent-child similarity in how emotion network interacts with other brain regions during movie viewing is associated with youth's better emotional adjustment including less negative affect, lower anxiety, and greater ego resilience. Interestingly, these associations are only significant among families with higher cohesion, but not among those with lower cohesion. Our findings provide novel evidence that parent-child shared neural processes to emotional situations can confer benefits to children, and underscore the importance of considering specific family contexts in which parent-child neural similarity may be beneficial or detrimental to children's development, highlighting a crucial direction for future research.


Assuntos
Ajustamento Emocional , Emoções , Humanos , Feminino , Adolescente , Adulto , Criança , Masculino , Ansiedade , Encéfalo/diagnóstico por imagem , Relações Pais-Filho
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