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1.
J Neurosci Res ; 102(1): e25265, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38284863

RESUMO

The olfactory working memory capacity (OWMC) paradigm is able to detect cognitive deficits in 5XFAD mice (an animal model of Alzheimer's disease [TG]) as early as 3 months of age, while other behavioral paradigms detect cognitive deficits only at 4-5 months of age. Therefore, we aimed to demonstrate that the OWMC paradigm is more sensitive and consistent in the early detection of declines in cognitive function than other commonly used behavioral paradigms. The prefrontal cortex (PFC), retrosplenial cortex (RSC), subiculum (SUB), and amygdala (AMY) of 5XFAD mice were harvested and subjected to immunostaining to detect the expression of ß-amyloid (Aß). Additionally, we compared the performance of 3-month-old male 5XFAD mice on common behavioral paradigms for assessing cognitive function (i.e., the open field [OF] test, novel object recognition [NOR] test, novel object location [NOL] test, Y-maze, and Morris water maze [MWM]) with that on the OWMC task. In the testing phase of the OWMC task, we varied the delay periods to evaluate the working memory capacity (WMC) of wild-type (WT) mice. Significant amyloid plaque deposition was observed in the PFC, RSC, SUB, and AMY of 3-month-old male 5XFAD mice. However, aside from the OWMC task, the other behavioral tests failed to detect cognitive deficits in 5XFAD mice. Additionally, to demonstrate the efficacy of the OWMC task in assessing WMC, we varied the retention delay periods; we found that the WMC of WT mice decreased with longer delay periods. The OWMC task is a sensitive and robust behavioral assay for detecting changes in cognitive function.


Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Disfunção Cognitiva , Masculino , Animais , Camundongos , Memória de Curto Prazo , Cognição , Disfunção Cognitiva/diagnóstico , Placa Amiloide
2.
Eur Radiol ; 34(2): 1292-1301, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37589903

RESUMO

OBJECTIVES: To explore the added value of arterial enhancement fraction (AEF) derived from dual-energy computed tomography CT (DECT) to conventional image features for diagnosing cervical lymph node (LN) metastasis in papillary thyroid cancer (PTC). METHODS: A total of 273 cervical LNs (153 non-metastatic and 120 metastatic) were recruited from 92 patients with PTC. Qualitative image features of LNs were assessed. Both single-energy CT (SECT)-derived AEF (AEFS) and DECT-derived AEF (AEFD) were calculated. Correlation between AEFD and AEFS was determined using Pearson's correlation coefficient. Multivariate logistic regression analysis with the forward variable selection method was used to build three models (conventional features, conventional features + AEFS, and conventional features + AEFD). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. RESULTS: Abnormal enhancement, calcification, and cystic change were chosen to build model 1 and the model provided moderate diagnostic performance with an area under the ROC curve (AUC) of 0.675. Metastatic LNs demonstrated both significantly higher AEFD (1.14 vs 0.48; p < 0.001) and AEFS (1.08 vs 0.38; p < 0.001) than non-metastatic LNs. AEFD correlated well with AEFS (r = 0.802; p < 0.001), and exhibited comparable performance with AEFS (AUC, 0.867 vs 0.852; p = 0.628). Combining CT image features with AEFS (model 2) and AEFD (model 3) could significantly improve diagnostic performances (AUC, 0.865 vs 0.675; AUC, 0.883 vs 0.675; both p < 0.001). CONCLUSIONS: AEFD correlated well with AEFS, and exhibited comparable performance with AEFS. Integrating qualitative CT image features with both AEFS and AEFD could further improve the ability in diagnosing cervical LN metastasis in PTC. CLINICAL RELEVANCE STATEMENT: Arterial enhancement fraction (AEF) values, especially AEF derived from dual-energy computed tomography, can help to diagnose cervical lymph node metastasis in patients with papillary thyroid cancer, and complement conventional CT image features for improved clinical decision making. KEY POINTS: • Metastatic cervical lymph nodes (LNs) demonstrated significantly higher arterial enhancement fraction (AEF) derived from dual-energy computed tomography (DECT) and single-energy CT (SECT)-derived AEF (AEFS) than non-metastatic LNs in patients with papillary thyroid cancer. • DECT-derived AEF (AEFD) correlated significantly with AEFS, and exhibited comparable performance with AEFS. • Integrating qualitative CT images features with both AEFS and AEFD could further improve the differential ability.


Assuntos
Neoplasias da Glândula Tireoide , Tomografia Computadorizada por Raios X , Humanos , Câncer Papilífero da Tireoide/patologia , Metástase Linfática/patologia , Tomografia Computadorizada por Raios X/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos
3.
Mol Biol Rep ; 51(1): 415, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472517

RESUMO

Estrogen regulates a wide range of neuronal functions in the brain, such as dendritic spine formation, remodeling of synaptic plasticity, cognition, neurotransmission, and neurodevelopment. Estrogen interacts with intracellular estrogen receptors (ERs) and membrane-bound ERs to produce its effect via genomic and non-genomic pathways. Any alterations in these pathways affect the number, size, and shape of dendritic spines in neurons associated with psychiatric diseases. Increasing evidence suggests that estrogen fluctuation causes changes in dendritic spine density, morphology, and synapse numbers of excitatory and inhibitory neurons differently in males and females. In this review, we discuss the role of estrogen hormone in rodents and humans based on sex differences. First, we explain estrogen role in learning and memory and show that a high estrogen level alleviates the deficits in learning and memory. Secondly, we point out that estrogen produces a striking difference in emotional memories in men and women, which leads them to display sex-specific differences in underlying neuronal signaling. Lastly, we discuss that fluctuations in estrogen levels in men and women are related to neuropsychiatric disorders, including schizophrenia, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BPD), major depressive disorder (MDD), substance use disorder (SUD), and anxiety disorders.


Assuntos
Transtorno do Espectro Autista , Transtorno Depressivo Maior , Humanos , Feminino , Masculino , Transtorno do Espectro Autista/genética , Caracteres Sexuais , Transtorno Depressivo Maior/metabolismo , Estrogênios/metabolismo , Sinapses/metabolismo , Emoções
4.
BMC Biol ; 21(1): 171, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37568146

RESUMO

BACKGROUND: Working memory capacity impairment is an early sign of Alzheimer's disease, but the underlying mechanisms remain unclear. Clarifying how working memory capacity is affected will help us better understand the pathological mechanism of Alzheimer's disease. We used the olfactory working memory capacity paradigm to evaluate memory capacity in 3-month-old 5XFAD (an animal model of Alzheimer's disease) mice. Immunofluorescence staining of the prefrontal cortex was performed to detect the number of FOS-positive neurons, calmodulin-dependent protein kinase II-positive neurons, and glutamate decarboxylase-positive neurons in the prelimbic cortex and infralimbic cortex. A chemogenetic method was then used to modulate the inhibition and activation of excitatory neurons in the prelimbic cortex of wild-type and 5XFAD mice and to measure the memory capacity of mice. RESULTS: Working memory capacity was significantly diminished in 5XFAD mice compared to littermate wild-type mice. Neuronal activation of the prelimbic cortex, but not the infralimbic cortex, was attenuated in 5XFAD mice performing the olfactory working memory capacity task. Subsequently, the FOS-positive neurons were co-localized with both calmodulin-dependent protein kinase II-positive neurons and glutamate decarboxylase-positive neurons. The results showed that the activation of excitatory neurons in the prelimbic cortex was correlated with working memory capacity in mice. Our results further demonstrate that the chemogenetic inhibition of prelimbic cortex excitatory neurons resulted in reduced working memory capacity in wild-type mice, while the chemogenetic activation of prelimbic cortex excitatory neurons improved the working memory capacity of 5XFAD mice. CONCLUSION: The diminished activation of prelimbic cortex excitatory neurons in 5XFAD mice during task performance is associated with reduced working memory capacity, and activation modulation of excitatory neurons by chemogenetic methods can improve memory capacity impairment in 5XFAD mice. These findings may provide a new direction for exploring Alzheimer's disease therapeutic approaches.


Assuntos
Doença de Alzheimer , Memória de Curto Prazo , Camundongos , Animais , Memória de Curto Prazo/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Glutamato Descarboxilase/metabolismo , Neurônios/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos
5.
Cancer Sci ; 114(7): 2860-2870, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37094904

RESUMO

High-risk neuroblastoma (HR-NB) is an aggressive childhood cancer that responds poorly to currently available therapies and is associated with only about a 50% 5-year survival rate. MYCN amplification is a critical driver of these aggressive tumors, but so far there have not been any approved treatments to effectively treat HR-NB by targeting MYCN or its downstream effectors. Thus, the identification of novel molecular targets and therapeutic strategies to treat children diagnosed with HR-NB represents an urgent unmet medical need. Here, we conducted a targeted siRNA screening and identified TATA box-binding protein-associated factor RNA polymerase I subunit D, TAF1D, as a critical regulator of the cell cycle and proliferation in HR-NB cells. Analysis of three independent primary NB cohorts determined that high TAF1D expression correlated with MYCN-amplified, high-risk disease and poor clinical outcomes. TAF1D knockdown more robustly inhibited cell proliferation in MYCN-amplified NB cells compared with MYCN-non-amplified NB cells, as well as suppressed colony formation and inhibited tumor growth in a xenograft mouse model of MYCN-amplified NB. RNA-seq analysis revealed that TAF1D knockdown downregulates the expression of genes associated with the G2/M transition, including the master cell-cycle regulator, cell-cycle-dependent kinase 1 (CDK1), resulting in cell-cycle arrest at G2/M. Our findings demonstrate that TAF1D is a key oncogenic regulator of MYCN-amplified HR-NB and suggest that therapeutic targeting of TAF1D may be a viable strategy to treat HR-NB patients by blocking cell-cycle progression and the proliferation of tumor cells.


Assuntos
Neuroblastoma , Humanos , Animais , Camundongos , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/patologia , Proliferação de Células/genética , Divisão Celular , Fase G2 , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
6.
Funct Integr Genomics ; 23(4): 309, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37735249

RESUMO

Estrogen (E2) modulates the synaptic structure and plasticity in the hippocampus. Previous studies showed that E2 fluctuations during various phases of the menstrual cycle produce subtle neurosynaptic changes that impact women's behavior, emotion, and cognitive functions. In this study, we explored the transcriptome of the hippocampus via RNA-seq (RNA-sequencing) between proestrus (PE) and diestrus (DE) stages in young female rats to determine the effect of E2 of PE and DE stages on hippocampal gene expression. We identified 238 genes (at 1.5-fold-change selection criteria, FDR adjusted p-value < 0.05) as differentially expressed genes (DEGs) that responded to E2 between PE and DE stages. Functional analysis based on Gene Ontology (GO) revealed that a higher E2 level corresponded to an increase in gene transcription among most of the DEGs, suggesting biological mechanisms operating differentially in the hippocampus of female rats between PE and DE stages in the estrus cycle; while analysis with Kyoto Encyclopedia of Genes and Genomes database (KEGG) found that the DEGs involving neuroactive ligand-receptor interaction, antigen processing, cell adhesion molecules, and presentation were upregulated in PE stage, whereas DEGs in pathways relating to bile secretion, coagulation cascades, osteoclast differentiation, cysteine and methionine metabolism were upregulated in DE stage of the estrus cycle. The high-fold expression of DEGs was confirmed by a follow-up quantitative real-time PCR. Our findings in this current study have provided fundamental information for further dissection of neuro-molecular mechanisms in the hippocampus in response to E2 fluctuation and its relationship with disorders.


Assuntos
Cisteína , Transcriptoma , Humanos , Animais , Feminino , Ratos , Estrogênios , Estro , Hipocampo
7.
Small ; 19(18): e2207227, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36720006

RESUMO

Developing efficient and robust metal-nitrogen-carbon electrocatalysts for oxygen reduction reaction (ORR) is of great significance for the application of hydrogen-oxygen fuel cells and metal-air batteries. Herein, a coordination engineering strategy is developed to improve the ORR kinetics and stability of cobalt-nitrogen-carbon (Co-N-C) electrocatalysts by grafting the oxygen-rich graphene quantum dots (GQDs) onto the zeolite imidazole frameworks (ZIFs) precursors. The optimized oxygen-rich GQDs-functionalized Co-N-C (G-CoNOC) electrocatalyst demonstrates an increased mass activity, nearly two times higher than that of pristine defective Co-N-C electrocatalyst, and retains a stability of 90.0% after 200 h, even superior to the commercial Pt/C. Comprehensive investigations demonstrate that the GQDs coordination can not only decrease carbon defects of Co-N-C electrocatalysts, improving the electron transfer efficiency and resistance to the destructive free radicals from H2 O2 , but also optimize the electronic structure of atomic Co active site to achieve a desired adsorption energy of OOH- , leading to enhanced ORR kinetics and stability by promoting further H2 O2 reduction, as confirmed by theoretical calculations and experimental results. Such a coordination engineering strategy provides a new perspective for the development of highly active noble-metal-free electrocatalysts for ORR.

8.
BMC Med Imaging ; 23(1): 25, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36740672

RESUMO

PURPOSE: To study the influence of sex, age and thyroid function indices on dual-energy computed tomography (DECT)-derived quantitative parameters of thyroid in patients with or without Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: A total of 198 consecutive patients who underwent DECT scan of neck due to unilateral thyroid lesions were retrospectively enrolled. Iodine concentration (IC), total iodine content (TIC) and volume of normal thyroid lobe were calculated. Influences of sex, age and thyroid function indices on DECT-derived parameters in overall study population, subgroup patients with, and those without HT were assessed using Mann-Whitney U test, Student's T-test, and Spearman correlation analyses, respectively, as appropriate. RESULTS: HT group showed significantly lower IC and TIC, while higher volume than No-HT group (all p < 0.001). The volume was larger in male than that in female in overall study population and No-HT group (p = 0.047 and 0.010, respectively). There was no significant difference in any DECT-derived parameters between low (≤ 35 years) and high (> 35 years) age group in all three groups (all p > 0.05). TPOAb and TgAb correlated positively with IC and TIC, and negatively with volume in overall study population (all p < 0.05). TPOAb and TgAb also correlated positively with IC in HT group (p = 0.002 and 0.007, respectively). CONCLUSION: DECT-derived parameters of thyroid differed significantly between patients with and without HT. Sex and thyroid function indices could affect the DECT-derived parameters. Aforementioned physiological factors should be considered when analyzing the DECT-derived parameters of thyroid.


Assuntos
Doença de Hashimoto , Iodo , Humanos , Masculino , Feminino , Estudos Retrospectivos , Doença de Hashimoto/diagnóstico por imagem , Doença de Hashimoto/patologia , Tomografia
9.
Acta Radiol ; 64(7): 2268-2276, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35502811

RESUMO

BACKGROUND: Dual-energy computed tomography (DECT) can provide objective evaluation of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). PURPOSE: To investigate the relationship between quantitative parameters acquired from DECT and histopathological prognostic factors in LHSCC. MATERIAL AND METHODS: A total of 65 patients with LHSCC who underwent arterial phase and venous phase DECT scans were retrospectively enrolled. Iodine concentration (IC) and normalized IC (NIC) of the tumor were calculated in both the arterial (ICA and NICA) and venous (ICV and NICV) phases, and compared among different pathological grades, T stages, and lymph node stages. Receiver operating characteristic (ROC) curves were generated to evaluate their diagnostic performance. RESULTS: There were significantly differences on ICA and NICA among three pathological grades (ICA, P = 0.001; NICA, P = 0.002). For differentiating moderately and poorly differentiated from well-differentiated LHSCC using ICA and NICA, the areas under curve (AUCs) were 0.753 and 0.726, respectively. High T stage (T3/4) LHSCC showed significantly higher ICA (P = 0.012) and NICA (P = 0.005) than low T stage (T1/2) LHSCC. The AUCs of the ICA and NICA were 0.674 and 0.703, respectively, in discriminating high from low T stage LHSCC. Lymph node metastasis (LNM)-positive (N1/2/3) LHSCC showed significantly higher ICA (P = 0.008) and NICA (P = 0.003) than LNM-negative (N0) LHSCC. For discriminating the LNM-positive from the LNM-negative group using ICA and NICA, the AUCs were 0.697 and 0.744, respectively. CONCLUSION: ICA and NICA might be helpful in assessing histopathological prognostic factors in patients with LHSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Tomografia Computadorizada por Raios X , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Metástase Linfática/diagnóstico por imagem
10.
Cancer Cell Int ; 21(1): 143, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653358

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to exert crucial functions in regulating the progression of human cancers. However, the function and mechanism of long intergenic non-protein coding RNA 01089 (LINC01089) in non-small cell lung cancer (NSCLC) have not been revealed. METHODS: The expression level of LINC01089, microRNA (miRNA, miR)-152-3p and phosphatase and tensin homolog deleted onc hromosome ten (PTEN) mRNA was detected by quantitative real-time PCR (qRT-PCR). After gain-of-function and loss-of-function models were established with NSCLC cell lines, the proliferation, migration and invasion of NSCLC cells were detected by cell counting kit-8 (CCK-8) assay, scratch healing assay, Transwell assay, respectively. Dual luciferase reporter assay was employed to validate the binding relationship between miR-152-3p and LINC01089 or the 3'UTR of PTEN. Western blot was used to detect PTEN expression in NSCLC cells after LINC01089 and miR-152-3p were selectively modulated. RESULTS: LINC01089 was down-regulated in NSCLC tissues and cells. Functional experiments showed that knockdown of LINC01089 could promote the proliferation, migration and invasion of NSCLC cells, while over-expression of LINC01089 had the opposite effects. miR-152-3p was identified as a functional target for LIN01089, and miR-152-3p could reverse the function of LINC01089. Additionally, LINC01089 could up-regulate the expression level of PTEN via repressing miR-152-3p. CONCLUSIONS: Down-regulation of LINC01089 promoted the progression of NSCLC through regulating miR-152-3p/PTEN axis.

11.
Nano Lett ; 20(11): 8015-8023, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33063511

RESUMO

Drawing inspiration from biology, neuromorphic systems are of great interest in direct interaction and efficient processing of analogue signals in the real world and could be promising for the development of smart sensors. Here, we demonstrate an artificial sensory neuron consisting of an InGaZnO4 (IGZO4)-based optical sensor and NbOx-based oscillation neuron in series, which can simultaneously sense the optical information even beyond the visible light region and encode them into electrical impulses. Such artificial vision sensory neurons can convey visual information in a parallel manner analogous to biological vision systems, and the output spikes can be effectively processed by a pulse coupled neural network, demonstrating the capability of image segmentation out of a complex background. This study could facilitate the construction of artificial visual systems and pave the way for the development of light-driven neurorobotics, bioinspired optoelectronics, and neuromorphic computing.


Assuntos
Redes Neurais de Computação , Visão Ocular , Células Receptoras Sensoriais
12.
Neurobiol Dis ; 136: 104715, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31843707

RESUMO

Cisplatin, a commonly used chemotherapy drug, can increase the survival rate of cancer patients. However, it often causes various side effects, including neuronal deficit-induced cognitive impairment. Considering that curcumin is effective in neuronal protection, the action of curcumin on cognitive improvement was evaluated in cisplatin-treated C57BL/6 mice in the present study. Our results first showed that curcumin restored impaired cognitive behaviors. Consistent with this, neurogenesis and synaptogenesis were improved by curcumin. In addition, cisplatin-induced dysfunction of apoptosis-related proteins was partly reversed by curcumin. Moreover, cisplatin-induced autophagy was enhanced by curcumin. Our results also indicated that cisplatin induced autophagy through the endoplasmic reticulum (ER) stress-mediated ATF4-Akt-mTOR signaling pathway. Curcumin activated AMPK-JNK signaling, which mediated both mTOR inhibition and Bcl-2 upregulation and in turn enhanced autophagy and suppressed apoptosis, respectively. In contrast, pretreatment with the autophagy inhibitor 3-methyladenine (3-MA) completely abolished the effects of curcumin on cognitive improvement and improved neurogenesis, synaptogenesis and autophagy. Our results show that cognitive improvement induced by curcumin during chemotherapy is mediated by the enhancement of hippocampal autophagy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/toxicidade , Autofagia/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Curcumina/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Autofagia/fisiologia , Cisplatino/toxicidade , Disfunção Cognitiva/patologia , Curcumina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
14.
Microb Cell Fact ; 18(1): 94, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138294

RESUMO

BACKGROUND: Flavone C-glycosides are difficult to be deglycosylated using traditional chemical methods due to their solid carbon-carbon bond between sugar moieties and aglycones; however, some bacteria may easily cleave this bond because they generate various specific enzymes. RESULTS: A bacterial strain, named W12-1, capable of deglycosylating orientin, vitexin, and isovitexin to their aglycones, was isolated from human intestinal bacteria in this study and identified as Enterococcus faecalis based on morphological examination, physiological and biochemical identification, and 16S rDNA sequencing. The strain was shown to preferentially deglycosylate the flavone C-glycosides on condition that the culture medium was short of carbon nutrition sources such as glucose and starch, and its deglycosylation efficiency was negatively correlated with the content of the latter two substances. CONCLUSION: This study provided a new bacterial resource for the cleavage of C-glycosidic bond of flavone C-glycosides and reported the carbon nutrition sources reduction induced deglycosylation for the first time.


Assuntos
Enterococcus faecalis/metabolismo , Fezes/microbiologia , Flavonas/metabolismo , Microbioma Gastrointestinal , Glicosídeos/metabolismo , Intestinos/microbiologia , Adulto , Apigenina/metabolismo , Carbono/metabolismo , Enterococcus faecalis/classificação , Enterococcus faecalis/genética , Enterococcus faecalis/isolamento & purificação , Flavonoides/metabolismo , Glucosídeos/metabolismo , Humanos , Masculino , RNA Ribossômico 16S , Análise de Sequência de RNA
16.
Drug Dev Ind Pharm ; 42(9): 1424-33, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26984179

RESUMO

Liposomes have successfully been used for decades to encapsulate and protect drugs that are prone to deactivation in the body. The present study aimed to demonstrate the use of liposomes to encapsulate cordycepin, an adenosine analog that quickly loses its activity in vivo. The cordycepin-loaded liposomes were prepared by the ammonium sulfate gradient approach, and its in vitro and in vivo antitumour activities were evaluated using BEL-7402 cells and hepatocellular carcinoma H22 transplanted tumors, respectively. An MTT assay was used to observe the cytotoxicity of cells treated with cordycepin and cordycepin-loaded liposomes in vitro. High-content screening (HSC) was carried out using Hoechst 33342 to detect apoptotic cells and the ratio of cells in different cell cycle stages. The data demonstrated that both the cordycepin and the cordycepin-loaded liposomes resulted in clear cytotoxicity with IC50 values of 18.97 and 29.39 µg/mL, respectively. The latter showed significantly strong inhibitory effects on H22 tumor growth in mice, while the former did not show any inhibitory effects on tumor growth. In addition, the HSC assay showed that the cordycepin-loaded liposomes resulted in a higher rate of apoptosis than the cordycepin alone in BEL-7402 cells. Further data analysis revealed that the cells treated with cordycepin-loaded liposomes were predominately arrested at the G2/M phase (p < 0.05), while those treated with cordycepin alone were arrested in the G0/G1 phase (p < 0.05). In conclusion, these results suggest that liposomes can enhance and maintain the in vivo anti-tumor activity of cordycepin.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Desoxiadenosinas/farmacologia , Lipossomos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos
17.
Planta Med ; 81(3): 185-92, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25590367

RESUMO

Syzygium aromaticum has been widely used in traditional medicine. Our study investigated the safety and antidepressant-like effects of the essential oil of S. aromaticum after acute or long-term treatment. Using GC-MS, a total of eight volatile constituents were identified in the essential oil of S. aromaticum. The single LD50 was approximately 4500 mg/kg based on a 24-h acute oral toxicity study. In a long-term repeated toxicity study of this essential oil (100, 200, and 400 mg/kg, p. o.), only 400 mg/kg induced a significant decrease in body weight. In addition, no significant changes in relative organ weights and histopathological analysis were observed in all doses of essential oil-treated mice compared with the control group. Furthermore, acute S. aromaticum essential oil administration by gavage exerted antidepressant-like effects in the forced swimming test (200 mg/kg, p < 0.05) and tail suspension test (100 and 200 mg/kg, p < 0.05). Long-term S. aromaticum essential oil treatment via gavage significantly increased sucrose preference (50 mg/kg, p < 0.05; 100 and 200 mg/kg, p < 0.01) as well as elevated the protein levels of hippocampal p-ERK, p-CREB, and brain-derived neurotrophic factor in mice exposed to chronic unpredictable mild stress. These results confirmed the safety of the essential oil of S. aromaticum and suggested that its potent antidepressant-like property might be attributed to the improvement in the hippocampal pERK1/2-pCREB-BDNF pathway in rats exposed to chronic unpredictable mild stress.


Assuntos
Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Óleos Voláteis/uso terapêutico , Fitoterapia , Estresse Psicológico/tratamento farmacológico , Syzygium/química , Animais , Antidepressivos/farmacologia , Proteína de Ligação a CREB , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Preferências Alimentares , Elevação dos Membros Posteriores , Masculino , Camundongos Endogâmicos ICR , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos Sprague-Dawley , Sacarose/administração & dosagem , Natação
18.
Metab Brain Dis ; 30(6): 1495-503, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26183613

RESUMO

Neurotrophic factors are well-known to be involved in the pathophysiology of depression and treatment of antidepressants. Brain-derived neurotrophic factor (BDNF), one of the most widely distributed and the most highly studied neurotrophic factors, has been demonstrated to play an important role in the pathophysiology of depression and the mechanism of antidepressants. According to the previous studies, we found that animal tissues were dissected for BDNF measurement mainly in daytime. Considering the circadian rhythm of BDNF expression, our present study evaluated the circadian variations in behaviors, serum corticosterone concentrations, hippocampal BDNF expression and neuronal cell proliferation in mice exposed to chronic mild stress (CMS), one of the most widely used depression-like animal models. Our results provided the first evidence that the difference of BDNF expression and neuronal cell proliferation between CMS and control mice underwent an oscillation related to the circadian variations (maximum at 20:00 h, minimum at 12:00 h or 16:00 h), while the difference of sucrose preference and first feeding latency was not affected by circadian rhythm. This oscillation difference was attributed to the relative constant BDNF expression and cell proliferation in CMS mice and the fluctuating BDNF expression and cell proliferation in control mice. CMS exposure might destroy the circadian rhythm of BDNF expression and cell proliferation in hippocampus of normal individual. Our present study suggests that animal decapitation at 20:00 h is the best time for BDNF-related measurement in CMS experiment, since the difference reaches the maximum.


Assuntos
Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células , Ritmo Circadiano , Depressão/metabolismo , Depressão/psicologia , Anedonia , Animais , Peso Corporal , Corticosterona/sangue , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurônios , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Sacarose
19.
Molecules ; 20(9): 15781-96, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26343630

RESUMO

As a classical herb pair in clinics of traditional Chinese medicine, Curcumae Rhizoma-Sparganii Rhizoma (HP CR-SR) is used for activating blood circulation to remove blood stasis. The essential components in HP CR-SR and its single herbs were comparatively analyzed using gas chromatography-mass spectrometry data. 66, 22, and 54 components in volatile oils of Curcumae Rhizoma, Sparganii Rhizoma, and HP CR-SR were identified, and total contents accounted for 75.416%, 91.857%, and 79.553% respectively. The thirty-eight components were found in HP CR-SR, and not detected in single herbs Curcumae Rhizoma and Sparganii Rhizoma. The highest radical trapping action was seen by an essential oil of HP CR-SR (IC50 = 0.59 ± 0.04 mg/mL). Furthermore, the HP CR-SR essential oil showed more remarkable cytotoxicity on tumor cell lines than that of the single herbs Curcumae Rhizoma and Sparganii Rhizoma in a dose-dependent manner: IC50 values showing 32.32 ± 5.31 µg/mL (HeLa), 34.76 ± 1.82 µg/mL (BGC823), 74.84 ± 1.66 µg/mL (MCF-7), 66.12 ± 11.23 µg/mL (SKOV3), and 708.24 ± 943.91 µg/mL (A549), respectively. In summary, the essential oil of HP CR-SR is different from any one of Curcumae Rhizoma and Sparganii Rhizoma, nor simply their superposition, and HP CR-SR oil presented more remarkable anticancer and antioxidant activities compared with Curcumae Rhizoma and Sparganii Rhizoma oils.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Curcuma/química , Óleos Voláteis/química , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Óleos Voláteis/farmacologia , Rizoma/química
20.
Pharm Biol ; 53(5): 767-72, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25431325

RESUMO

CONTEXT: The roots of Berchemia lineate (L.) DC. (Rhamnaceae) have been long used as a remedy for the treatment of some diseases in Guangxi Province, China. OBJECTIVE: The present study investigates the hepatoprotective effect of Berchemia lineate ethanol extract (BELE) on CCl4-induced acute liver damage in mice. MATERIALS AND METHODS: Effect of BELE administrated for 7 consecutive days was evaluated in mice by the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), albulin (ALB), globulin (GLB), and total protein (TP) levels, as well as liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Moreover, histopathological examinations were also taken. RESULTS: Compared with the model group, administration of 400 mg/kg BELE for 7 d in mice significantly decreased the serum ALT (56.25 U/L), AST (297.67 U/L), ALP (188.20 U/L), and TBIL (17.90 mol/L), along with the elevation of TP (64.67 g/L). In addition, BELE (100, 200, and 400 mg/kg, i.g.) treated mice recorded a dose-dependent increment of SOD (291.17, 310.32, and 325.67 U/mg prot) and reduction of MDA (7.27, 6.77, and 5.33 nmol/mg prot) levels. Histopathological examinations also confirmed that BELE can ameliorate CCl4-induced liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation. DISCUSSION AND CONCLUSION: The results indicated that BELE possessed remarkable protective effect against acute hepatotoxicity and oxidative injuries induced by CCl4, and that the hepatoprotective effects of BELE may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.


Assuntos
Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Etanol/uso terapêutico , Extratos Vegetais/uso terapêutico , Rhamnaceae , Animais , Tetracloreto de Carbono/antagonistas & inibidores , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Etanol/isolamento & purificação , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/uso terapêutico
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