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BACKGROUND: Schisandra chinensis, an ancient member of the most basal angiosperm lineage which is known as the ANITA, is a fruit-bearing vine with the pharmacological effects of a multidrug system, such as antioxidant, anti-inflammatory, cardioprotective, neuroprotective, anti-osteoporosis effects. Its major bioactive compound is represented by lignans such as schisandrin. Molecular characterization of lignan biosynthesis in S. chinensis is of great importance for improving the production of this class of active compound. However, the biosynthetic mechanism of schisandrin remains largely unknown. RESULTS: To understand the potential key catalytic steps and their regulation of schisandrin biosynthesis, we generated genome-wide transcriptome data from three different tissues of S. chinensis cultivar Cheongsoon, including leaf, root, and fruit, via long- and short-read sequencing technologies. A total of 132,856 assembled transcripts were generated with an average length of 1.9 kb and high assembly completeness. Overall, our data presented effective, accurate gene annotation in the prediction of functional pathways. In particular, the annotation revealed the abundance of transcripts related to phenylpropanoid biosynthesis. Remarkably, transcriptome profiling during fruit development of S. chinensis cultivar Cheongsoon revealed that the phenylpropanoid biosynthetic pathway, specific to coniferyl alcohol biosynthesis, showed a tendency to be upregulated at the postfruit development stage. Further the analysis also revealed that the pathway forms a transcriptional network with fruit ripening-related genes, especially the ABA signaling-related pathway. Finally, candidate unigenes homologous to isoeugenol synthase 1 (IGS1) and dirigent-like protein (DIR), which are subsequently activated by phenylpropanoid biosynthesis and thus catalyze key upstream steps in schisandrin biosynthesis, were identified. Their expression was increased at the postfruit development stage, suggesting that they may be involved in the regulation of schisandrin biosynthesis in S. chinensis. CONCLUSIONS: Our results provide new insights into the production and accumulation of schisandrin in S. chinensis berries and will be utilized as a valuable transcriptomic resource for improving the schisandrin content.
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Lignanas , Schisandra , Antioxidantes , Frutas/química , Frutas/genética , Lignanas/análise , TranscriptomaRESUMO
OBJECTIVE: To investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based prospective longitudinal study enrolled 109 patients with AD. All patients with AD were evaluated at 3-month intervals to investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. OUTCOME MEASURE: The main outcome measure was time-to-progression from AD to incident psychosis. The thickness or volume of medial temporal lobe structures (i.e., the hippocampus, entorhinal cortex, and parahippocampus) were measured using magnetic resonance imaging and the Freesurfer automated segmentation pipeline at baseline. RESULTS: Multivariate Cox proportional hazards regression analysis revealed that a decreased cortical thickness or volume of medial temporal region was associated with a higher risk of incident psychosis in patients with AD. The hazard ratios for decreased cortical thickness of the left entorhinal cortex and decreased cortical volume of the right hippocampus were 4.291 (95% confidence interval [CI], 1.196-15.384) and 2.680 [(CI, 1.003-1.196]), respectively. CONCLUSION: Our study revealed that decreased cortical thickness or volume of medial temporal sub-regions is a risk factor for incident psychosis in patients with AD. A careful assessment of the thickness or volume of the medial temporal lobe structures in AD may improve early detection and intervention of psychosis in AD.
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Doença de Alzheimer , Transtornos Psicóticos , Lobo Temporal , Doença de Alzheimer/complicações , Humanos , Incidência , Estudos Longitudinais , Imageamento por Ressonância Magnética , Tamanho do Órgão , Estudos Prospectivos , Transtornos Psicóticos/epidemiologia , Fatores de Risco , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologiaRESUMO
AIM: Categorical syndromes such as schizophrenia could be a combination of many continuous mental structure phenotypes including several personality development/degeneration dimensions. This study investigated the heritability and familiality of symptom check list (SCL) psychopathologic dimensions in Korean schizophrenia linkage disequilibrium families. METHOD: We recruited 204 probands (with schizophrenia) with their parents and siblings whenever possible. We used the SCL questionnaire to measure psychopathologic dimensions. The heritability of symptomatic dimensions in 543 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Psychopathologic dimensions in the 543 family members were compared with those in 307 healthy unrelated controls to measure familiality on using analysis of variance (ANOVA) analysis. RESULTS: Five of the nine SCL variables were significantly heritable and were included in the subsequent analyses. The three groups (control, unaffected first-degree relative, schizophrenia patient) were found to be significantly different with regard to the expected order of average group scores for all heritable dimensions. CONCLUSION: Aberrations in several symptomatic dimensions could contribute to the complexity of schizophrenia syndrome as a result of genetic-environment coaction or interaction in spite of some limitations (recruited family, phenotyping).
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Povo Asiático/psicologia , Família/psicologia , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIM: The purpose of this study was to determine whether regionally distributed medial temporal cortex thickness (or hippocampal volume) and frontal lobe volume are independently associated with the onset of Alzheimer's disease (AD) with psychosis. METHODS: We identified 26 AD patients with psychosis (AD+P) and 48 AD patients without psychosis (AD-P) from the Memory Impairment Clinic at Pusan National University Hospital in South Korea. They were matched for age, gender, duration of AD, and Clinical Dementia Rating sum of box score. All participants met the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for probable AD. Psychosis was diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of AD. All participants underwent 3-T magnetic resonance imaging, and 3-D magnetization-prepared rapid gradient echo sequence was acquired for each. The FreeSurfer version 5.1 software package was used to analyze cortical thickness and volume on 3-D T1 -weighted images. anova was used to investigate the differences in cortical thickness and the volume of the total frontal cortex, total temporal cortex, and subregions of the medial temporal cortex between groups after age, gender, years of education, Clinical Dementia Rating sum of box score, duration of AD, and total intracranial volume were controlled for. Furthermore, we added the total frontal volume as an additional variable to investigate whether the association between the medial temporal cortex and AD+P is independent of the frontal cortex. RESULTS: We found that both left and right hippocampal volume were smaller in AD+P than in AD-P. In particular, there was a significant difference in right hippocampal volume between the AD+P and AD-P groups after total frontal volume was added as an additional variable. CONCLUSION: We found that more severe hippocampal atrophy is associated with AD+P than with AD-P. In addition, atrophy of the right hippocampus remained significant among AD+P after adjustment for frontal volume. These findings suggest that right hippocampal atrophy is independently associated with AD+P.
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Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Imageamento por Ressonância Magnética/métodos , Transtornos Psicóticos/complicações , Idoso , Doença de Alzheimer/complicações , Atrofia , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Humanos , Imageamento Tridimensional/métodos , Masculino , Testes de Estado Mental e Demência/estatística & dados numéricosRESUMO
MAIN CONCLUSION: A genome-wide survey of Catharanthus roseus receptor-like kinase1-like kinases (CrRLK1Ls) in rice revealed that the pattern of expression by some CrRLK1Ls is controlled by drought or circadian rhythms. This is probably accomplished through the functioning of Gigantea ( OsGI ). Such findings provide a novel angle for using CrRLK1Ls to study the drought-stress response and circadian regulation. The 17 CrRLK1L members of a novel RLK family have been identified in Arabidopsis. Each carries a putative extracellular carbohydrate-binding malectin-like domain. However, their roles in rice, a widely consumed staple food, are not well understood. To investigate the functions of CrRLK1Ls in rice, we utilized phylogenomics data obtained through anatomical and diurnal meta-expression analyses. This information was integrated with a large set of public microarray data within the context of the rice CrRLK1L family phylogenic tree. Chromosomal locations indicated that 3 of 16 genes were tandem-duplicated, suggesting possible functional redundancy within this family. However, integrated diurnal expression showed functional divergence between two of three genes, i.e., peak expression was detected during the day for OsCrRLK1L2, but during the night for OsCrRLK1L3. We found it interesting that OsCrRLK1L2 expression was repressed in osgigantea (osgi) mutants, which suggests that it could function downstream of OsGI. Network analysis associated with OsCrRLK1L2 and OsGI suggested a novel circadian regulation mechanism mediated by OsGI. In addition, two of five OsCrRLK1Ls preferentially expressed in the roots were stimulated by drought, suggesting a potential role for this family in water-use efficiency. This preliminary identification of CrRLK1Ls and study of their expression in rice will facilitate further functional classifications and applications in plant production.
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Catharanthus/genética , Oryza/genética , Proteínas Quinases/genética , Arabidopsis/genética , Mapeamento Cromossômico , Ritmo Circadiano , Secas , Perfilação da Expressão Gênica , Genoma de Planta , Oryza/enzimologia , Filogenia , Estresse FisiológicoRESUMO
Rice (Oryza sativa) is one of the most important staple food crops for more than half of the world's population. The demand is increasing for food security because of population growth and environmental challenges triggered by climate changes. This scenario has led to more interest in developing crops with greater productivity and sustainability. The process of genetic transformation, a major tool for crop improvement, utilizes promoters as one of its key elements. Those promoters are generally divided into three types: constitutive, spatiotemporal, and condition-dependent. Transcriptional control of a constitutive promoter often leads to reduced plant growth, due to a negative effect of accumulated molecules during cellular functions or energy consumption. To maximize the effect of a transgene on transgenic plants, it is better to use condition-dependent or tissue-specific promoters. However, until now, those types have not been as widely applied in crop biotechnology. In this review, we introduce and discuss four groups of tissue-specific promoters (50 promoters in total) and six groups of condition-dependent promoters (27 promoters). These promoters can be utilized to fine-tune desirable agronomic traits and develop crops with tolerance to various stresses, enhanced nutritional value, and advanced productivity.
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Regulação da Expressão Gênica de Plantas , Oryza/genética , Regiões Promotoras Genéticas , Biotecnologia , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismoRESUMO
We investigated the effects of silicon (Si) application on rice plants (Oryza sativa L.) and its responses in the regulation of jasmonic acid (JA) during wounding stress. Endogenous JA was significantly higher in wounded rice plants than in non-wounded. In contrast, Si treatment significantly reduced JA synthesis as compared to non-Si applications under wounding stress. mRNA expression of O. sativa genes showed down-regulation of lipoxygenase, allene oxide synthase 1, allene oxide synthase 2, 12-oxophytodienoate reductase 3, and allene oxide cyclase upon Si application and wounding stress as compared to non-Si-treated wounded rice plants. The physical injury-induced-oxidative stress was modulated by Si treatments, which resulted in higher catalase, peroxidase, and polyphenol oxidase activities as compared with non-Si-treated plants under wounding stress. The higher Si accumulation in rice plants also reduced the level of lipid peroxidation, which helped the rice plants to protect it from wounding stress. In conclusion, Si accumulation in rice plants mitigated the adverse effects of wounding through regulation of antioxidants and JA.
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Ciclopentanos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Oryza/efeitos dos fármacos , Oryza/genética , Oxilipinas/metabolismo , Proteínas de Plantas/genética , Silício/metabolismo , Silício/farmacologia , Oryza/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The purpose of this study was to investigate the differences in subjective acute effects of alcohol and naltrexone among those who prefer spicy food to varying degrees. Acute biphasic alcohol effects scale (BAES), visual analogue scale for craving (VAS-C), blood alcohol concentration (BAC) and food preference scale were measured in 26 men. Repeated measures ANOVA (2 preference groups×4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in naltrexone condition (N+) (P<0.001), but not in non-naltrexone condition (N-). Furthermore, repeated measures ANOVA (2 drug groups×4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in strong preference for spicy food (SP) (P<0.001), but not in lesser preference for spicy food (LP). The paired t-test revealed that significant suppression of the stimulative subscale of BAES was observed at 15 min (P<0.001) and 30 min (P<0.001) after drinking when N+ compared with N- in SP. For those who prefer spicy food, the stimulative effect of acute alcohol administration was suppressed by naltrexone. This result suggests that the effect of naltrexone may vary according to spicy food preference.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoolismo/tratamento farmacológico , Preferências Alimentares/efeitos dos fármacos , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Adulto , Capsaicina/farmacologia , Humanos , Masculino , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Fármacos do Sistema Sensorial/farmacologia , Inquéritos e Questionários , Adulto JovemRESUMO
AIMS: An association between white matter hyperintensities (WMH) and cognitive dysfunction has long been recognized. However, subjects with identically appearing WMH on magnetic resonance imaging present with a wide variance in cognitive function ranging from normal cognition to dementia. The aim of this study was to compare cortical atrophy and integrity of white matter of patients with subcortical vascular dementia of Binswanger type (SVaD-BT) with those of the normal cognition group with WMH (ncWMH). METHODS: Eleven patients with SVaD-BT and 11 age-, sex-, education- and grade of WMH-matched ncWMH underwent magnetic resonance imaging, including 3-D volumetric images for cortical atrophy and diffusion tensor imaging for integrity of white matter. RESULTS: Compared to ncWMH, SVaD-BT patients showed cortical atrophies in frontal (i.e. frontal pole, precentral gyrus and frontal medial cortex) and occipital areas (i.e. lingual gyrus) followed by atrophies in temporal (i.e. fusiform cortex and middle temporal gyrus) areas. Along with cortical atrophies, reduced integrity with low fractional anisotropy and high mean diffusivity values in genu and splenium of the corpus callosum were detected in SVaD-BT patients. CONCLUSIONS: Our findings suggest that cognitive decline from ncWMH to SVaD-BT may be associated with cortical atrophy and reduced integrity of white matter.
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Córtex Cerebral/patologia , Transtornos Cognitivos/patologia , Demência Vascular/patologia , Substância Branca/patologia , Idoso , Atrofia/patologia , Transtornos Cognitivos/etiologia , Demência Vascular/complicações , Imagem de Tensor de Difusão , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
OBJECTIVE: Face-to-face evaluation is the most important in psychiatric evaluation, but smart healthcare, including non-face-to-face evaluation, can be beneficial considering the situation in which face-to-face evaluation is limited or the preventive aspect of mental illness. In this paper, we aimed to check whether mental health screening tests have the same significance as paper-based tests even when collected through mobile applications. METHODS: A smart mental healthcare screening test was conducted on the 1,327 community subjects. We measured two indicators of depression (Patient Health Questionnaire 9-item scale, PHQ-9) and anxiety (Generalized Anxiety Disorder 7-item scale, GAD-7) to check mental health conditions. RESULTS: The average Cronbach's alpha value of the PHQ-9 questionnaire was good at 0.870. As a result of PHQ-9's principal component analysis, one component with an eigenvalue of 1 or more was identified, which is suitable to be described as a single factor. The average Cronbach's alpha value of the GAD-7 was 0.919. The structural validity of the GAD-7 was confirmed through principal component analysis. CONCLUSION: Our results show that PHQ-9 and GAD-7 scales performed through mobile applications can have the same meaning as paper-based tests. Surveys using a tablet PC, or smartphone application can monitor residents' mental health and accumulate data. Based on these data, smart mental health management can check the mental health of residents and treat mental illness in connection with medical services.
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Sugammadex, a selective antagonist of steroidal non-depolarizing neuromuscular blocking agents, has been used in children in limited circumstances. However, neither pharmacokinetics (PKs) nor recovery profile of sugammadex for intense neuromuscular blockade reversal in children have been reported. This prospective study aimed to obtain a PK model of sugammadex and evaluate its efficacy and safety for intense neuromuscular blockade reversal in children. Forty children (age, 2-17 years) who underwent surgery that required early neuromuscular blockade reversal were enrolled. After neuromuscular blockade with 1 mgâkg-1 of rocuronium, sugammadex (2, 4, and 8 mgâkg-1 ) or a conventional dose of neostigmine (0.03 mgâkg-1 ) was administered randomly after confirmation of zero post-tetanic count. The plasma concentrations of rocuronium and sugammadex were measured 2 min after rocuronium injection; immediately before, 2, 5, 15, 60, 120, 240, and 480 min after the study drug injection. Response to train-of-four stimulation was continuously recorded. Noncompartmental analysis and population PK modeling were performed. For pharmacodynamics, the recovery profile was measured. Three-compartment PK model was established for sugammadex. The median (interquartile range [IQR]) time from injection of 8 mgâkg-1 of sugammadex to recovery of T4 /T1 greater than or equal to 0.9 at train-of-four stimulation was 1.1 (IQR: 0.88-1.8) min. No adverse events related to sugammadex were observed. We present a PK analysis of sugammadex for rocuronium-induced intense neuromuscular blockade reversal in children with its recovery profile. The time to recover T4 /T1 greater than or equal to 0.9 at train-of-four stimulation with 8 mgâkg-1 of sugammadex was less than 3 min and comparable to that in adults.
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Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Adulto , Criança , Humanos , Pré-Escolar , Adolescente , Sugammadex/efeitos adversos , Rocurônio , Bloqueio Neuromuscular/efeitos adversos , gama-Ciclodextrinas/efeitos adversos , Estudos Prospectivos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Androstanóis/efeitos adversos , Androstanóis/farmacocinética , República da CoreiaRESUMO
Background: Sugammadex is known to reverse neuromuscular blockade induced by non-depolarizing agents. In children, the recommended dose for reversal of moderate neuromuscular blockade is 2 mg/kg. We investigated the pharmacokinetics and pharmacodynamics of sugammadex in Korean children. Methods: Children (2-17 years of age) undergoing brain or spine surgery were enrolled and randomly assigned to control (neostigmine) and 2, 4, or 8 mg/kg sugammadex groups. Following induction of anesthesia and monitoring of the response to train-of-four stimulation, 1 mg/kg rocuronium was intravenously administered. Upon reappearance of the second twitch to train-of-four stimulation, the study drug was administered according to group allocation. The plasma concentrations of rocuronium and sugammadex were serially measured at nine predefined time points following study drug administration. To determine efficacy, we measured the time elapsed from drug administration to recovery of T4/T1 ≥ 0.9. For pharmacokinetics, non-compartmental analysis was performed and we monitored adverse event occurrence from the time of study drug administration until 24 h post-surgery. Results: Among the 29 enrolled participants, the sugammadex (2 mg/kg) and control groups showed recovery times [median (interquartile range)] of 1.3 (1.0-1.9) and 7.7 (5.3-21.0) min, respectively (p = 0.002). There were no significant differences in recovery time among the participants in sugammadex groups. The pharmacokinetics of sugammadex were comparable to those of literature findings. Although two hypotensive events related to sugammadex were observed, no intervention was necessary. Conclusion: The findings of this pharmacokinetic analysis and efficacy study of sugammadex in Korean children indicated that sugammadex (2 mg/kg) may be safely administered for reversing moderate neuromuscular blockade. Some differences in pharmacokinetics of sugammadex were observed according to age. Clinical Trial Registration: http://clinicaltrials.gov (NCT04347486).
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Background: To investigate the relationships of plasma transthyretin levels with amyloid beta deposition and medial temporal atrophy in amnestic mild cognitive impairment. Methods: This is a cross-sectional study of association of subjects with amnestic mild cognitive impairment. Plasma transthyretin levels, brain magnetic resonance imaging, and 18F-florbetaben positron emission tomography were simultaneously measured in subjects with amnestic mild cognitive impairment. Results: Plasma transthyretin levels were positively associated with amyloid beta deposition in global (r = 0.394, P = .009), frontal cortex (r = 0.316, P = .039), parietal cortex (r = 0.346, P = .023), temporal cortex (r = 0.372, P = .014), occipital cortex (r = 0.310, P = .043), right posterior cingulate (r = 0.350, P = .021), left precuneus (r = 0.314, P = .040), and right precuneus (r = 0.398, P = .008). No association between plasma transthyretin level and medial temporal sub-regional atrophies was found. Conclusions: Our findings of positive association of plasma transthyretin levels with global and regional amyloid beta burden suggest upregulation of transthyretin level as a reactive response to amyloid beta deposition during the early stages of the Alzheimer's disease process.
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In Arabidopsis, the NMD-defective mutants upf1-5 and upf3-1 are characterized by dwarfism, curly leaves and late flowering. These phenotypes are similar to those of mutants showing constitutive pathogenesis-related (PR) gene expression, salicylic acid (SA) accumulation and, subsequently, resistance to pathogens. The disease symptoms of upf1-5 and upf3-1 mutants were observed following infection with the virulent pathogen Pst DC3000 with the aim of determining whether the loss of nonsense-mediated mRNA decay (NMD) is involved in disease resistance. These mutant plants showed not only enhanced resistance to Pst DC3000, but also elevated levels of endogenous SA, PR gene transcripts and WRKY transcripts. UPF1 and UPF3 expression was down-regulated in Pst DC3000-infected Arabidopsis plants, but the expression of various NMD target genes was up-regulated. The expression of 10 defense-related genes was elevated in cycloheximide (CHX)-treated plants. The transcriptional ratios of eight of these 10 defense-related genes in CHX-treated to non-treated plants were lower in NMD-defective mutants than in the wild-type plants. These eight defense-related genes are possibly regulated by the NMD mechanism, and it is clear that an alternatively spliced transcript of WRKY62, which contains a premature termination codon, was regulated by this mechanism. Taken together, our results suggest that UPF1 and UPF3, which are key NMD factors, may act as defense-related regulators associated with plant immunity.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/imunologia , Degradação do RNAm Mediada por Códon sem Sentido/genética , Imunidade Vegetal/genética , RNA Helicases/metabolismo , Arabidopsis/enzimologia , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Cicloeximida/farmacologia , Resistência à Doença/efeitos dos fármacos , Resistência à Doença/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas/genética , Transferases Intramoleculares/metabolismo , Mutação/genética , Degradação do RNAm Mediada por Códon sem Sentido/efeitos dos fármacos , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Imunidade Vegetal/efeitos dos fármacos , Pseudomonas syringae/efeitos dos fármacos , RNA Helicases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ácido Salicílico/metabolismoRESUMO
Stress induces structural plasticity in neurons of the adult central nervous system (CNS) and alters the levels of cellular production of reactive oxygen species (ROS), and these changes might involve modifications of the antioxidant defense system. This study investigated whether acute stress altered the expression pattern of peroxiredoxin (Prx) III, which is an antioxidant enzyme that controls cytokine-induced peroxide levels. Prx III immunoreactivity was upregulated in the pyramidal neurons of the hippocampus and in the motor neurons of the spinal cord in an acute immobilization stress (AIS) model. In addition, we tested whether the transcription factor Foxo3a was necessary for the expression of Prx III. The depletion of Foxo3a led to a marked reduction of Prx III and a compensatory enhancement of mitochondrial superoxide dismutase (Mn-SOD) in PC12 cells. The results of this study suggest that Foxo3a mediates the neuronal levels of expression of Prx III and the levels of expression of Mn-SOD in mitochondria. These mechanisms may play an important role in neuroprotection against oxidative stress. Furthermore, Prx III upregulation might be an useful approach for the management of stress.
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Fatores de Transcrição Forkhead/metabolismo , Hipocampo/enzimologia , Imobilização/fisiologia , Imobilização/psicologia , Peroxirredoxina III/metabolismo , Estresse Psicológico/metabolismo , Animais , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Hipocampo/citologia , Humanos , Masculino , Mitocôndrias/enzimologia , Células PC12 , Peroxirredoxina III/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia , Medula Espinal/enzimologia , Superóxido Dismutase/metabolismo , Regulação para CimaRESUMO
Objective: This study investigated the association between gray matter volume and the treatment response to antipsychotic medication in patients with Alzheimer's disease (AD). Methods: We included 26 AD patients with delusions from the Memory Impairment Center of the Pusan National University Hospital in South Korea. All participants underwent baseline brain magnetic resonance imaging and took risperidone as an antipsychotic medication for 6 weeks. Gray matter volumes were measured using voxel-based morphometry at baseline. Treatment response with respect to delusional symptoms was defined as the change in delusion item scores in the Korean version of the Neuropsychiatry Inventory (K-NPI), from baseline to 6 weeks later. A voxel-based multiple linear regression model integrated with statistical parametric mapping was used to investigate the association between gray matter volume and treatment response after controlling for covariates. Results: The treatment response was significantly positively correlated with gray matter volume in the temporal lobe (both the fusiform gyri and the left superior and inferior temporal gyri) and the limbic system (the left parahippocampal gyrus and left amygdala) after controlling for age, sex, education level, total intracranial volume, risperidone dosage, baseline Korean version of the Mini-Mental Status Examination scores, and baseline K-NPI scores for the delusion and non-delusion domains (P < .001, uncorrected, KE > 100 voxels). Conclusion: Our findings suggest that specific gray matter volumes, including those of the temporal region and the limbic system, may affect treatment response to antipsychotic medication in terms of delusional symptoms in patients with AD.
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Pancreatic cancers are classified based on where they occur, and are grouped into those derived from exocrine and those derived from neuroendocrine tumors, thereby experiencing different anticancer effects under medication. Therefore, it is necessary to develop anticancer drugs that can inhibit both types. To this end, we developed a heparin-taurocholate conjugate, i.e., LHT, to suppress tumor growth via its antiangiogenic activity. Here, we conducted a study to determine the anticancer efficacy of LHT on pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET), in an orthotopic animal model. LHT reduced not only proliferation of cancer cells, but also attenuated the production of VEGF through ERK dephosphorylation. LHT effectively reduced the migration, invasion and tube formation of endothelial cells via dephosphorylation of VEGFR, ERK1/2, and FAK protein. Especially, these effects of LHT were much stronger on PNET (RINm cells) than PDAC (PANC1 and MIA PaCa-2 cells). Eventually, LHT reduced ~50% of the tumor weights and tumor volumes of all three cancer cells in the orthotopic model, via antiproliferation of cancer cells and antiangiogenesis of endothelial cells. Interestingly, LHT had a more dominant effect in the PNET-induced tumor model than in PDAC in vivo. Collectively, these findings demonstrated that LHT could be a potential antipancreatic cancer medication, regardless of pancreatic cancer types.
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BACKGROUND: A long-term follow-up study in patients with amnestic mild cognitive impairment (aMCI) is needed to elucidate the association between regional brain volume and psychopathological mechanisms of Alzheimer's disease with psychosis (ADâ+âP). OBJECTIVE: The purpose of this study was to investigate the effect of the thickness of the angular cingulate cortex (ACC) on the risk of ADâ+âP conversion in patients with aMCI. METHODS: This was a hospital-based prospective longitudinal study including 174 patients with aMCI. The main outcome measure was time-to-progression from aMCI to ADâ+âP. Subregions of the ACC (rostral ACC, rACC; caudal ACC, cACC) and hippocampus (HC) were measured as regions of interest with magnetic resonance imaging and the Freesurfer analysis at baseline. Survival analysis with time to incident ADâ+âP as an event variable was calculated with Cox proportional hazards models using the subregions of the ACC and HC as a continuous variable. RESULTS: Cox proportional hazard analyses showed that the risk of ADâ+âP was associated with sub-regional ACC thickness but not HC volume: reduced cortical thickness of the left cACC (HR [95%CI], 0.224 [0.087-0.575], pâ=â0.002), right cACC (HR [95%CI], 0.318 [0.132-0.768], pâ=â0.011). This association of the cACC with the risk of AD also remained significant when adjusted for HC volume. CONCLUSION: We found that reduced cortical thickness of the cACC is a predictor of aMCI conversion to ADâ+âP, independent of HC, suggesting that the ACC plays a vital role in the underlying pathogenesis of ADâ+âP.
Assuntos
Doença de Alzheimer/patologia , Amnésia/complicações , Disfunção Cognitiva/patologia , Progressão da Doença , Giro do Cíngulo/patologia , Testes Neuropsicológicos/estatística & dados numéricos , Transtornos Psicóticos/complicações , Idoso , Encéfalo/patologia , Feminino , Hipocampo/patologia , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: Even though the importance of stress-coping, there is no reliable and valid scale to measure the stress-coping behavior yet. The purpose of this study is to explore the psychometric properties of Behavioral Checklist for Coping with Stress (BCCS). METHODS: A total of 458 subjects including healthy subjects and patients with bipolar or depressive disorders were analyzed. The reliability and validity of BCCS were examined by Chronbach's alpha and exploratory factor analysis using Principal Component Analysis. In order to evaluate criterion-related validity, the Pearson's correlation analyses between factors of BCCS and relevant scales were performed. RESULTS: BCCS showed good Chronobach's alpha (0.695-0.833) and had acceptable validity. Factor 1 and factor 4 of BCCS were negatively correlated with depression, anxiety and positivity correlated with task and problem-solving, avoidance, tension-releasing copings in common. Factor 2 and 3 were positively correlated with impulsivity, emotionality, avoidance, behavioral and verbal aggression and tension-releasing copings in common. Different from factor 2, factor 3 was positively correlated with depression, anxiety and anger-suppression. CONCLUSION: The results of this study suggest that this BCCS might be a reliable and valid scale for measuring stress-coping behaviors. This scale could facilitate research to investigate clinical implications related to behavioral stress-coping.
RESUMO
This case report aimed to describe various psychiatric manifestation and treatment course in a patient with DiGeorge syndrome. Psychiatric symptoms and treatment course in a female patient with DiGeorge syndrome were described. This patient showed psychotic symptoms, mood symptoms, and intellectual disability. As well as various psychiatric symptoms, treatment response and sensitivity of side effect by antipsychotics were different from typical characteristics in psychiatric disorders. This case suggests that the genetic defect in DiGeorge syndrome might have a great association with psychiatric problems and response of antipsychotics.