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1.
Sci Data ; 10(1): 861, 2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049462

RESUMO

Despite the importance of hypothalamic neurocircuits in regulating homeostatic and survival-related behaviors, our understanding of the intrinsic molecular identities of neural components involved in these complex multi-synaptic interactions remains limited. In this study, we constructed a Cre recombinase-dependent pseudorabies virus (PRVs) capable of crossing synapses, coupled with transcriptome analysis of single upstream neurons post-infection. By utilizing this retrograde nuclear Connect-seq (nuConnect-seq) approach, we generated a single nuclei RNA-seq (snRNA-seq) dataset of 1,533 cells derived from the hypothalamus of CRH-IRES-Cre (CRH-Cre) mice. To ensure the technical validity of our nuConnect-seq dataset, we employed a label transfer technique against an integrated reference dataset of postnatal mouse hypothalamus comprising 152,524 QC-passed cells. The uniqueness of our approach lies in the integration of diverse datasets for validation, providing a more nuanced diversity of hypothalamic cell types. The presented validated dataset may deepen our understanding of hypothalamic neurocircuits and underscore the essential role of comprehensive integrated transcriptomic data for technical validity.


Assuntos
Herpesvirus Suídeo 1 , Transcriptoma , Animais , Camundongos , Perfilação da Expressão Gênica/métodos , Herpesvirus Suídeo 1/genética , Hipotálamo , Neurônios/metabolismo
2.
Exp Mol Med ; 55(8): 1659-1671, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37524867

RESUMO

Stress responses, which are crucial for survival, are evolutionally conserved throughout the animal kingdom. The most common endocrine axis among stress responses is that triggered by corticotropin-releasing hormone neurons (CRHNs) in the hypothalamus. Signals of various stressors are detected by different sensory systems and relayed through individual neural circuits that converge on hypothalamic CRHNs to initiate common stress hormone responses. To investigate the neurocircuitry mechanisms underlying stress hormone responses induced by a variety of stressors, researchers have recently developed new approaches employing retrograde transsynaptic viral tracers, providing a wealth of information about various types of neural circuits that control the activity of CRHNs in response to stress stimuli. Here, we review earlier and more recent findings on the stress neurocircuits that converge on CRHNs, focusing particularly on olfactory systems that excite or suppress the activities of CRHNs and lead to the initiation of stress responses. Because smells are arguably the most important signals that enable animals to properly cope with environmental changes and survive, unveiling the regulatory mechanisms by which smells control stress responses would provide broad insight into how stress-related environmental cues are perceived in the animal brain.


Assuntos
Hormônio Liberador da Corticotropina , Hipotálamo , Animais , Hormônio Liberador da Corticotropina/metabolismo , Hipotálamo/metabolismo , Hormônios , Encéfalo/metabolismo
3.
Nat Commun ; 14(1): 1486, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932069

RESUMO

For survival, it is crucial for eating behaviours to be sequenced through two distinct seeking and consummatory phases. Heterogeneous lateral hypothalamus (LH) neurons are known to regulate motivated behaviours, yet which subpopulation drives food seeking and consummatory behaviours have not been fully addressed. Here, in male mice, fibre photometry recordings demonstrated that LH leptin receptor (LepR) neurons are correlated explicitly in both voluntary seeking and consummatory behaviours. Further, micro-endoscope recording of the LHLepR neurons demonstrated that one subpopulation is time-locked to seeking behaviours and the other subpopulation time-locked to consummatory behaviours. Seeking or consummatory phase specific paradigm revealed that activation of LHLepR neurons promotes seeking or consummatory behaviours and inhibition of LHLepR neurons reduces consummatory behaviours. The activity of LHLepR neurons was increased via Neuropeptide Y (NPY) which acted as a tonic permissive gate signal. Our results identify neural populations that mediate seeking and consummatory behaviours and may lead to therapeutic targets for maladaptive food seeking and consummatory behaviours.


Assuntos
Fome , Receptores para Leptina , Camundongos , Masculino , Animais , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Hipotálamo/metabolismo , Neurônios/metabolismo , Comportamento Consumatório , Leptina/metabolismo
4.
Cells ; 10(3)2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668388

RESUMO

Ginseng is a traditional herbal medicine in eastern Asian countries. Most active constituents in ginseng are prepared via fermentation or organic acid pretreatment. Extracellular vesicles (EVs) are released by most organisms from prokaryotes to eukaryotes and play central roles in intra- and inter-species communications. Plants produce EVs upon exposure to microbes; however, their direct functions and utility for human health are barely known, except for being proposed as delivery vehicles. In this study, we isolated EVs from ginseng roots (GrEVs) or the culture supernatants of ginseng cells (GcEVs) derived from Panax ginseng C.A. Meyer and investigated their biological effects on human skin cells. GrEV or GcEV treatments improved the replicative senescent or senescence-associated pigmented phenotypes of human dermal fibroblasts or ultraviolet B radiation-treated human melanocytes, respectively, by downregulating senescence-associated molecules and/or melanogenesis-related proteins. Based on comprehensive lipidomic analysis using liquid chromatography mass spectrometry, the lipidomic profile of GrEVs differed from that of the parental root extracts, showing significant increases in 70 of 188 identified lipid species and prominent increases in diacylglycerols, some phospholipids (phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine), and sphingomyelin, revealing their unique vesicular properties. Therefore, our results imply that GEVs represent a novel type of bioactive and sustainable nanomaterials that can be applied to human tissues for improving tissue conditions and targeted delivery of active constituents.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Vesículas Extracelulares/efeitos dos fármacos , Espectrometria de Massas/métodos , Panax/química , Plantas Medicinais/química , Pele/efeitos dos fármacos , Proliferação de Células , Humanos
5.
Proc Natl Acad Sci U S A ; 117(8): 4375-4384, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32034095

RESUMO

The mouse brain contains about 75 million neurons interconnected in a vast array of neural circuits. The identities and functions of individual neuronal components of most circuits are undefined. Here we describe a method, termed "Connect-seq," which combines retrograde viral tracing and single-cell transcriptomics to uncover the molecular identities of upstream neurons in a specific circuit and the signaling molecules they use to communicate. Connect-seq can generate a molecular map that can be superimposed on a neuroanatomical map to permit molecular and genetic interrogation of how the neuronal components of a circuit control its function. Application of this method to hypothalamic neurons controlling physiological responses to fear and stress reveals subsets of upstream neurons that express diverse constellations of signaling molecules and can be distinguished by their anatomical locations.


Assuntos
Perfilação da Expressão Gênica/métodos , Neurônios/metabolismo , Animais , Hipotálamo/química , Hipotálamo/metabolismo , Camundongos , Neurônios/química , Proteínas/química , Proteínas/genética , Proteínas/metabolismo , Transcriptoma
6.
Hanguk Hosupisu Wanhwa Uiryo Hakhoe Chi ; 23(1): 17-26, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37496891

RESUMO

Purpose: This study was conducted to develop a hospice music therapist training program and to evaluate its effects. Methods: The educational program consisted of training on the theory of hospice and the theory and practice of hospice music therapy. The course lasted for 4 weeks, with 8 hours of training per week, and 33 music therapists completed the course. In order to assess the effectiveness of the course, participants' knowledge and confidence regarding hospice music therapy and readiness for hospice music therapy before and after education were measured. The statistical analysis was done using SPSS version 18.0 and the paired t-test was used to assess the effectiveness of the program. Results: The trainees showed significant improvements in knowledge (P<0.001) and confidence (P<0.001) in all areas of this course, as well as in readiness for hospice music therapy (P<0.001). Participants' satisfaction with the lectures was assessed using a 5-point Likert scale. The average score for all lecture areas exceeded 4 (yes), and the satisfaction level was mostly high. Students were most satisfied with the lectures on music therapy theory, followed in order by those on music therapy practice and hospice theory. Conclusion: This hospice music therapist training program is considered to be suitable because of its positive educational effects and the high satisfaction of participants with the lectures. In order to provide high-quality music therapy services to patients and their families, this training course should be regularly offered to cultivate competent music therapists, and the content of the education should be standardized and applied in various clinical settings.

7.
J Menopausal Med ; 25(2): 94-99, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31497579

RESUMO

OBJECTIVES: Vitamin D is regarded as one of the major nutrients that significantly influence bone metabolism. This study aims to look at the effect of supplementary vitamin D on bone mineral density (BMD) in female osteoporosis patients. METHODS: The retrospective hospital record review was performed on 282 patients who were diagnosed with osteoporosis and treated with selective estrogen receptor modulators (SERMs) between January 2015 and December 2016. Of these patients, 151 were treated with SERMs only while 131 were treated using both SERMs and vitamin D supplements. The BMD and any occurrence of osteoporotic fracture episode were investigated after one year. The result of two groups was compared to find the significance of vitamin D. RESULTS: Overall, improvement in BMD score was observed in 76% of the patients. The BMD of the SERMs only group improved by 3% in spine and 1% in the hip while that of the SERMs with vitamin D group improved by 6% and 1% respectively. Statistical significance was noticed in the spine only. One distal radius fracture and one single level vertebral fracture occurred in patients of SERMs group while two distal radius fractures occurred in SERMs with vitamin D group. There was no occurrence of around hip fracture in both groups. CONCLUSION: The result of the current study suggests that additional vitamin D may have some additive effect on improving BMD of the spine. Further study with the larger study population and the extended study period is recommended.

8.
Ann Surg Oncol ; 24(12): 3541-3548, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28819909

RESUMO

BACKGROUND: Mammography detects calcium deposits sensitively, but the specificity for differentiating malignancy from benign calcifications is low. Thus, we investigated whether adjunctive breast-specific gamma imaging (BSGI) has incremental value for detecting cancer in women with suspicious calcifications detected by mammography, and compared BSGI with adjunctive ultrasonography (US). METHODS: The medical records of women without a personal history of breast cancer who underwent mammography for breast evaluation from 2009 to 2014 were reviewed retrospectively. Patients who had calcifications detected by mammography, with a result of Breast Imaging Reporting and Data System (BI-RADS) categories 3-5, underwent adjunctive US and BSGI and were included in this study. A total of 302 breast lesions in 266 women (mean age ± standard deviation 49 ± 9 years) were selected for this study. RESULTS: For detecting breast cancer using mammography plus BSGI, the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating curve with 95% confidence intervals were 94% (91-96), 90% (86-93), 91% (87-94), 94% (90-96), and 0.92 (0.89-0.95), respectively. For mammography plus US, the respective values were 97% (94-98), 51% (46-57), 68% (63-73), 94% (90-96), and 0.74 (0.70-0.78). CONCLUSIONS: Adjunctive BSGI had higher specificity than adjunctive US without loss of sensitivity. This finding suggests that adjunctive BSGI may be a useful complementary initial imaging method to improve the detection of breast cancer in women who have calcifications with suspicious morphology at mammography.


Assuntos
Neoplasias da Mama/diagnóstico , Mama/patologia , Calcinose/diagnóstico , Mamografia/métodos , Cintilografia/métodos , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
9.
Asian J Psychiatr ; 25: 16-21, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28262140

RESUMO

Neurofeedback (NF) has been identified as a "possibly efficacious" treatment in current evidence-based reviews; therefore, more research is needed to determine its effects. The current study examined the potential additive effect of NF for children diagnosed with ADHD beginning a medication trial first. Thirty-six children (6-12 years) with a DSM-IV-TR diagnosis of ADHD were randomly assigned to an NF with medication (NF condition) or a medication only condition. Children in the NF group attended 20 twice-weekly sessions. Outcome measures included individual cognitive performance scores (ADS, K-WISC-III), ADHD rating scores completed by their parents (ARS, CRS) and brainwave indices of left and right hemispheres before and after NF treatment. Significant additive treatment effect in any of the symptom variables was found and a reduction of theta waves in both the right and left hemispheres was recorded in NF condition participants. However our randomized controlled study could not demonstrate superior effects of combined NF on intelligent functioning compared to the medication treatment only. This study suggested any possible evidence of positive and additive treatment effects of NF on brainwaves and ADHD symptomatology.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/terapia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Neurorretroalimentação/métodos , Avaliação de Resultados em Cuidados de Saúde , Ritmo Teta/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Terapia Combinada , Feminino , Humanos , Masculino
10.
BMC Plant Biol ; 15: 227, 2015 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-26384972

RESUMO

BACKGROUND: Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites sharing a common biosynthetic origin beginning with tyrosine. Many BIAs have potent pharmacological activities, and plants accumulating them boast long histories of use in traditional medicine and cultural practices. The decades-long focus on a select number of plant species as model systems has allowed near or full elucidation of major BIA pathways, including those of morphine, sanguinarine and berberine. However, this focus has created a dearth of knowledge surrounding non-model species, which also are known to accumulate a wide-range of BIAs but whose biosynthesis is thus far entirely unexplored. Further, these non-model species represent a rich source of catalyst diversity valuable to plant biochemists and emerging synthetic biology efforts. RESULTS: In order to access the genetic diversity of non-model plants accumulating BIAs, we selected 20 species representing 4 families within the Ranunculales. RNA extracted from each species was processed for analysis by both 1) Roche GS-FLX Titanium and 2) Illumina GA/HiSeq platforms, generating a total of 40 deep-sequencing transcriptome libraries. De novo assembly, annotation and subsequent full-length coding sequence (CDS) predictions indicated greater success for most species using the Illumina-based platform. Assembled data for each transcriptome were deposited into an established web-based BLAST portal ( www.phytometasyn.ca) to allow public access. Homology-based mining of libraries using BIA-biosynthetic enzymes as queries yielded ~850 gene candidates potentially involved in alkaloid biosynthesis. Expression analysis of these candidates was performed using inter-library FPKM normalization methods. These expression data provide a basis for the rational selection of gene candidates, and suggest possible metabolic bottlenecks within BIA metabolism. Phylogenetic analysis was performed for each of 15 different enzyme/protein groupings, highlighting many novel genes with potential involvement in the formation of one or more alkaloid types, including morphinan, aporphine, and phthalideisoquinoline alkaloids. Transcriptome resources were used to design and execute a case study of candidate N-methyltransferases (NMTs) from Glaucium flavum, which revealed predicted and novel enzyme activities. CONCLUSIONS: This study establishes an essential resource for the isolation and discovery of 1) functional homologues and 2) entirely novel catalysts within BIA metabolism. Functional analysis of G. flavum NMTs demonstrated the utility of this resource and underscored the importance of empirical determination of proposed enzymatic function. Publically accessible, fully annotated, BLAST-accessible transcriptomes were not previously available for most species included in this report, despite the rich repertoire of bioactive alkaloids found in these plants and their importance to traditional medicine. The results presented herein provide essential sequence information and inform experimental design for the continued elucidation of BIA metabolism.


Assuntos
Alcaloides/metabolismo , Benzilisoquinolinas/metabolismo , Magnoliopsida/genética , Proteínas de Plantas/genética , Transcriptoma , Berberidaceae/genética , Berberidaceae/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Magnoliopsida/metabolismo , Menispermaceae/genética , Menispermaceae/metabolismo , Dados de Sequência Molecular , Papaveraceae/genética , Papaveraceae/metabolismo , Proteínas de Plantas/metabolismo , Ranunculaceae/genética , Ranunculaceae/metabolismo , Análise de Sequência de DNA
11.
Int J Nanomedicine ; 9 Suppl 2: 67-78, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25565827

RESUMO

This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO2 (EN20(-)) (20 nm) or SiO2 (EN100(-)) 2(100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO2 particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO2 particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO2 (EN20(-))(20 nm) or SiO2 (EN100(-)) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO2 (EN20(-)) and SiO2 (EN100(-)) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex.


Assuntos
Coloides , Nanopartículas , Dióxido de Silício , Administração Oral , Animais , Coloides/administração & dosagem , Coloides/química , Coloides/toxicidade , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/toxicidade , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/administração & dosagem , Dióxido de Silício/química , Dióxido de Silício/toxicidade , Testes de Toxicidade Crônica
12.
Int J Nanomedicine ; 9 Suppl 2: 109-26, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25565830

RESUMO

Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnO(AE100[-])) or positively (ZnO(AE100[+])) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnO(AE100(-)) and ZnO(AE100(+)) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg.


Assuntos
Nanopartículas Metálicas , Óxido de Zinco , Administração Oral , Animais , Feminino , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Pâncreas/efeitos dos fármacos , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos , Distribuição Tecidual , Testes de Toxicidade , Óxido de Zinco/administração & dosagem , Óxido de Zinco/química , Óxido de Zinco/farmacocinética , Óxido de Zinco/toxicidade
13.
Complement Ther Med ; 20(6): 409-16, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23131371

RESUMO

BACKGROUND: Chemotherapy is the most distressing form of cancer treatment in oncology, but listening to music can be an adjuvant during chemotherapy. Monochord (MC) sounds are used in music therapy for the alleviation of pain, enhanced body perception, and relaxation. This study investigated the relaxation effect of MC sounds for patients during chemotherapy compared with progressive muscle relaxation (PMR), an established relaxation technique. METHODOLOGY/PRINCIPAL FINDINGS: Two randomized groups of patients were observed during chemotherapy. One group listened to recorded MC sounds (n=20) and the other group listened to recorded PMR (n=20). Each session was investigated pre and post using Spielberger's State Anxiety Inventory (SAI) and a questionnaire about the patient's physical and psychological states. Further, for the first and the last session, multivariate electroencephalogram (EEG) signals were recorded. Patients in both MC and PMR groups showed significant improvement in their physical and psychological states and in state anxiety. The EEG data showed that the MC and the PMR groups were associated with an increase of posterior theta (3.5-7.5 Hz) and a decrease of midfrontal beta-2 band (20-29.5 Hz) activity during the end phase of relaxation treatment. Further, the MC group was associated with decreased alpha band (8-12 Hz) activity in comparison with PMR group. CONCLUSIONS: This study shows that both listening to recorded MC sounds and practising PMR have a useful and comparable effect on gynaecologic oncological patients during chemotherapy, with partially overlapping but also notably divergent neural correlates. Future research should establish the systematic use of MC in oncological contexts.


Assuntos
Ansiedade/terapia , Musicoterapia , Música , Terapia de Relaxamento/métodos , Som , Estresse Fisiológico , Estresse Psicológico/terapia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Ansiedade/etiologia , Ondas Encefálicas , Eletroencefalografia , Feminino , Humanos , Pessoa de Meia-Idade , Relaxamento Muscular , Neoplasias/tratamento farmacológico , Neoplasias/psicologia , Relaxamento , Estresse Psicológico/etiologia , Inquéritos e Questionários
14.
Planta Med ; 78(14): 1536-42, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22872592

RESUMO

Platycodin D (PD) has been reported to control obesity in vivo. This study investigated the molecular mechanism of PD, focusing on its ability to decrease the expression of adipogenic factors through AMP-activated protein kinase α (AMPKα) in adipocytes and its ability to prevent abdominal fat accumulation in high-fat diet-induced obese C57BL/6 mice. The inhibitory effect of lipid accumulation in 3T3-L1 cells was measured by Oil Red O staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting. To determine the antiobesity effect in vivo, one group of mice were given a normal diet and the others were fed a high-fat diet for 8 weeks. The high-fat diet mice were then assigned to one of three subgroups: aminoimidazole carboxamide ribonucleotide (AICAR), vehicle, and PD. PD significantly reduced fat accumulation by inhibiting adipogenic signal transcriptional factors, such as peroxisome proliferator-activated receptor γ2 (PPARγ2) and CCAAT/enhancer binding protein α (C/EBPα), which functions via AMPK signaling, in vitro. PD reduced both body weight and fat volume; consequently, lipid metabolism was improved by increasing AMPKα, similar to AICAR, and reduced PPARγ2 and C/EBPα expression in adipose tissue. The results suggested that PD could be used to decrease the expression of adipogenic factors related to the AMPK pathway. Hence, PD could be an alternative treatment for controlling obesity by downregulating lipid accumulation.


Assuntos
Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , PPAR gama/efeitos dos fármacos , Platycodon/química , Saponinas/farmacologia , Triterpenos/farmacologia , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Dieta Hiperlipídica , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Estrutura Molecular , Obesidade Abdominal/prevenção & controle , PPAR gama/genética , PPAR gama/metabolismo , Raízes de Plantas/química , Ribonucleotídeos/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Triterpenos/química , Triterpenos/isolamento & purificação
15.
Plant Physiol ; 157(3): 1067-78, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21949209

RESUMO

Tyrosine aminotransferase (TyrAT) catalyzes the transamination of L-Tyr and α-ketoglutarate, yielding 4-hydroxyphenylpyruvic acid and L-glutamate. The decarboxylation product of 4-hydroxyphenylpyruvic acid, 4-hydroxyphenylacetaldehyde, is a precursor to a large and diverse group of natural products known collectively as benzylisoquinoline alkaloids (BIAs). We have isolated and characterized a TyrAT cDNA from opium poppy (Papaver somniferum), which remains the only commercial source for several pharmaceutical BIAs, including codeine, morphine, and noscapine. TyrAT belongs to group I pyridoxal 5'-phosphate (PLP)-dependent enzymes wherein Schiff base formation occurs between PLP and a specific Lys residue. The amino acid sequence of TyrAT showed considerable homology to other putative plant TyrATs, although few of these have been functionally characterized. Purified, recombinant TyrAT displayed a molecular mass of approximately 46 kD and a substrate preference for L-Tyr and α-ketoglutarate, with apparent K(m) values of 1.82 and 0.35 mm, respectively. No specific requirement for PLP was detected in vitro. Liquid chromatography-tandem mass spectrometry confirmed the conversion of L-Tyr to 4-hydroxyphenylpyruvate. TyrAT gene transcripts were most abundant in roots and stems of mature opium poppy plants. Virus-induced gene silencing was used to evaluate the contribution of TyrAT to BIA metabolism in opium poppy. TyrAT transcript levels were reduced by at least 80% in silenced plants compared with controls and showed a moderate reduction in total alkaloid content. The modest correlation between transcript levels and BIA accumulation in opium poppy supports a role for TyrAT in the generation of alkaloid precursors, but it also suggests the occurrence of other sources for 4-hydroxyphenylacetaldehyde.


Assuntos
Benzilisoquinolinas/metabolismo , Ópio/metabolismo , Papaver/enzimologia , Tirosina Transaminase/metabolismo , Benzilisoquinolinas/química , DNA Complementar/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Concentração de Íons de Hidrogênio , Cinética , Papaver/genética , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/isolamento & purificação , Tirosina Transaminase/genética , Tirosina Transaminase/isolamento & purificação
16.
J Neurosci ; 31(19): 7131-40, 2011 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-21562275

RESUMO

The environment in early life elicits profound effects on fetal brain development that can extend into adulthood. However, the long-lasting impact of maternal stress on emotional learning remains largely unknown. Here, we focus on amygdala-related learning processes in maternally stressed mice. In these mice, fear memory consolidation and certain related signaling cascades were significantly impaired, though innate fear, fear memory acquisition, and synaptic NMDA receptor expression in the amygdala were unaltered. In accordance with these findings, maintenance of long-term potentiation (LTP) at amygdala synapses, but not its induction, was significantly impaired in the maternally stressed animals. Interestingly, amygdala glucocorticoid receptor expression was reduced in the maternally stressed mice, and administration of glucocorticoids (GCs) immediately after fear conditioning and LTP induction restored memory consolidation and LTP maintenance, respectively, suggesting that a weakening of GC signaling was responsible for the observed impairment. Furthermore, microinfusion of a membrane-impermeable form of GC (BSA-conjugated GC) into the amygdala mimicked the restorative effects of GC, indicating that a nongenomic activity of GC mediates the restorative effect. Together, these findings suggest that prenatal stress induces long-term dysregulation of nongenomic GC action in the amygdala of adult offspring, resulting in the impairment of fear memory consolidation. Since modulation of amygdala activity is known to alter the consolidation of emotionally influenced memories allocated in other brain regions, the nongenomic action of GC on the amygdala shown herein may also participate in the amygdala-dependent modulation of memory consolidation.


Assuntos
Tonsila do Cerebelo/fisiologia , Medo/fisiologia , Glucocorticoides/metabolismo , Memória/fisiologia , Efeitos Tardios da Exposição Pré-Natal , Estresse Fisiológico/fisiologia , Estimulação Acústica , Análise de Variância , Animais , Western Blotting , Condicionamento Clássico/fisiologia , Eletrofisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Imuno-Histoquímica , Masculino , Camundongos , Fosforilação/fisiologia , Gravidez , Distribuição Aleatória
17.
J Agric Food Chem ; 57(16): 7513-22, 2009 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-19655726

RESUMO

Metabolite profiling and fingerprint analysis by (1)H NMR spectroscopy were used to identify potential biomarkers capable of distinguishing different ginseng species, varieties, and commercial products with the aim of establishing quality control code protocol based on biochemical phenotype. Principal component (PC) analyses of (1)H NMR spectra reliably discriminated between the various ginseng samples, demonstrating the potential utility of metabolomics in the natural health products industry. Four Asian ginseng varieties separated along the PC1 and PC2 axes, and four different Korean ginseng products were divided into two groups by PC1. A strong separation was also revealed between Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius). Glutamine, arginine, sucrose, malate, and myo-inositol were the major metabolites in ginseng samples tested in this study. Combined metabolite fingerprinting and profiling suggested that several compounds including glucose, fumarate, and various amino acids could serve as biomarkers for quality assurance in ginseng.


Assuntos
Medicamentos de Ervas Chinesas/química , Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Metabolômica/organização & administração , Panax/química , Medicamentos de Ervas Chinesas/metabolismo , Panax/metabolismo , Controle de Qualidade
18.
J Ethnopharmacol ; 120(2): 176-80, 2008 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-18762238

RESUMO

AIM OF THE STUDY: We created a new herbal formulation that mainly consists of the seeds of Lycium chinense, Cornus officinalis, Rubus coreanus, Cuscuta chinensis and Schizandra chinensis. These materials have been long used by Korean people as they are known to be good for health and sexual function; hence we could say that their safety have been proven in a certain sense. We investigated the effects of this herbal formulation on the penile erection and corpus cavernosum of spontaneous hypertensive male Rats (SHRs). MATERIALS AND METHODS: We used male SHRs aged 16 weeks as a model of hypertension. The treatment groups received once a day oral doses of KH-204 at either 100 or 300mg/kg per day for 4 weeks. Distilled water was administered to the control group. To investigate the penile erection, the intracavernosal pressure (ICP) and mean arterial pressure (MAP) were recorded in all groups. We analyzed the distribution of NOS by immunohistochemical staining and the expressions of nNOS and eNOS in the isolated corpus cavernosum were measured by Western blotting. RESULTS: In the control group, the ICP/MAP ratio was 14.9+/-1.4% after pelvic nerve stimulation. The ICP/MAP ratio was markedly increased in the treatment group with KH-204 100 or 300mg/kg, compared with the control group. Immunohistochemical staining for NOS showed that eNOS and nNOS were stained as a brown color. Compared with the control group, the NOS activities of KH-204 100 or 300mg/kg were significantly increased. Also, the penile expression levels of nNOS and eNOS in the KH-204 100 and 300mg/kg treatment groups were more increased, and this was significant, than those of the control group, as was determined by Western blotting. CONCLUSIONS: This study showed that the KH-204 herbal formulation enhances intracavernous pressure and NO-cGMP activity in penile tissues of SHR male rats.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Ereção Peniana/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Western Blotting , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Medicina Tradicional Coreana , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/efeitos dos fármacos , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Pênis/efeitos dos fármacos , Pênis/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos , Ratos Endogâmicos SHR , Sementes
19.
J Econ Entomol ; 101(6): 1960-6, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19133480

RESUMO

The toxicity to adult Sitophilus oryzae (L.) (Coleoptera: Curculionidae) of two cassia oils (Especial and true), four cinnamon oils (technical, #500, bark, and green leaf), and (E)-cinnamaldehyde and its 41 structurally related compounds was examined by residual and vapor-phase toxicity bioassays. Results were compared with those of dichlorvos. In residual bioassays, cassia and cinnamon oils exhibited good insecticidal activity. Based on 48-h LD50 values, the toxicity of allyl cinnmate (0.0003 mg/cm2) was comparable with that of dichlorvos (0.00025 mg/cm2). Potent insecticidal activity also was observed with benzaldehyde, beta-caryophyllene, cinnamonitrile, hydrocinnamyl acetate, (E)-4-hydroxycinnamic acid, and alpha-terpineol (LD50 = 0.003-0.009 mg/cm2). Structure-activity relationships indicate that types of functional groups rather than hydrophobicity or vapor pressure parameters seem to play a role in determining the toxicities to adult S. oryzae. In vapor-phase toxicity tests with weevils, these compounds were more effective in closed containers than in open ones. These results indicate that the effect of the compounds was largely a result of action in the vapor phase. Cassia and cinnamon oils and test compounds described merit further study as potential fumigants for the control of S. oryzae because of their greater activity as a fumigant.


Assuntos
Acroleína/análogos & derivados , Cinnamomum/química , Inseticidas , Óleos de Plantas , Gorgulhos , Acroleína/química , Animais , Cinnamomum zeylanicum/química , Fumigação , Inseticidas/química , Dose Letal Mediana , Resíduos de Praguicidas , Óleos de Plantas/química , Relação Estrutura-Atividade
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