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1.
J Org Chem ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39024340

RESUMO

Two general protocols for the regioselective electrochemically enabled sulfonylation cyclization of N-alkenylacrylamides with sodium sulfinates or sulfonyl hydrazides were described. These methods were carried out under mild, chemical oxidant-free, and transition-metal-free conditions with a broad substrate scope and good functional group tolerance to provide sulfonyl-containing 4-pyrrolin-2-ones, which is readily scalable to the gram scale.

2.
Epilepsia ; 64(10): 2667-2678, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37522416

RESUMO

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

3.
Hum Mol Genet ; 27(4): 625-637, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29294000

RESUMO

Paroxysmal kinesigenic dyskinesia (PKD) is a heterogeneous movement disorder characterized by recurrent dyskinesia attacks triggered by sudden movement. PRRT2 has been identified as the first causative gene of PKD. However, it is only responsible for approximately half of affected individuals, indicating that other loci are most likely involved in the etiology of this disorder. To explore the underlying causative gene of PRRT2-negative PKD, we used a combination strategy including linkage analysis, whole-exome sequencing and copy number variations analysis to detect the genetic variants within a family with PKD. We identified a linkage locus on chromosome 12 (12p13.32-12p12.3) and detected a novel heterozygous mutation c.956 T>G (p.319 L>R) in the potassium voltage-gated channel subfamily A member 1, KCNA1. Whole-exome sequencing in another 58 Chinese patients with PKD who lacked mutations in PRRT2 revealed another novel mutation in the KCNA1 gene [c.765 C>A (p.255 N>K)] within another family. Biochemical analysis revealed that the L319R mutant accelerated protein degradation via the proteasome pathway and disrupted membrane expression of the Kv1.1 channel. Electrophysiological examinations in transfected HEK293 cells showed that both the L319R and N255K mutants resulted in reduced potassium currents and respective altered gating properties, with a dominant negative effect on the Kv1.1 wild-type channel. Our study suggests that these mutations in KCNA1 cause the Kv1.1 channel dysfunction, which leads to familial PKD. The current study further extended the genotypic spectrum of this disorder, indicating that Kv1.1 channel dysfunction maybe one of the underlying defects in PKD.


Assuntos
Distonia/genética , Canal de Potássio Kv1.1/genética , Adulto , Povo Asiático , Variações do Número de Cópias de DNA , Feminino , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Linhagem
5.
World J Pediatr ; 20(1): 82-91, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36645641

RESUMO

BACKGROUND: The PACS gene family has been demonstrated to be related to intracellular vesicular trafficking. The phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy, intellectual disability/developmental delay, and malformations, such as facial abnormalities. METHODS: We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation sequencing. Detailed information obtained from these patients was analyzed along with that obtained from previously reported patients. RESULTS: With the inclusion of the newly diagnosed cases in this study, 103 cases with PACS gene family-related neurological diseases were reported, of which 43 were PACS2-related cases and the remaining were PACS1-related cases. Most patients had seizures, which have been reported to be effectively controlled by several types of anti-seizure medications (ASMs). The most efficacious and frequently prescribed ASMs included sodium valproate (43.3%, 13/30), oxcarbazepine/carbamazepine (26.7%, 8/30), and levetiracetam (20%, 6/30). Almost all patients had intellectual disability/developmental delay. The most common pathogenic missense variants were PACS1 p. Arg203Trp and PACS2 p.Glu209Lys. In addition, we report a patient carrying a likely pathogenic copy number variation (CNV) (de novo heterozygous deletion of chr14:105821380-106107443, 286 kilobase, destroyed part of the furin-binding region domain and the protein structure after it) with more severe and refractory late-onset epilepsy. CONCLUSIONS: The clinical phenotypes of the different PACS heterozygous missense variants were similar. The pathogenic variant sites of PACS1 and PACS2 were quite limited but located in different regions. A CNV destroying part of the PACS2 gene might also be pathogenic. These findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family. Video Abstract (MP4 65767 kb).


Assuntos
Epilepsia , Deficiência Intelectual , Humanos , Deficiência Intelectual/genética , Variações do Número de Cópias de DNA , Epilepsia/tratamento farmacológico , Epilepsia/genética , Fenótipo , Genótipo , Proteínas de Transporte Vesicular/genética
6.
J Cancer Res Clin Oncol ; 149(13): 12379-12391, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37436512

RESUMO

PURPOSE: To investigate the risk factors of second primary malignant tumor (SPMT) in patients with differentiated thyroid cancer (DTC) and establish a competing risk nomogram to predict the probability of SPMT occurrence. METHODS: We retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with DTC between 2000 and 2019. The Fine and Gray subdistribution hazard model was employed to identify SPMT risk factors in the training set and develop a competing risk nomogram. Model evaluation was performed using area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 112,257 eligible patients were included in the study and randomized into a training set (n = 112,256) and a validation set (n = 33,678). The cumulative incidence rate of SPMT was 15% (n = 9528). Age, sex, race, tumor multifocality, and TNM stage were independent risk factors of SPMT. The calibration plots showed good agreement between the predicted and observed SPMT risks. The 10-year AUCs of the calibration plots were 70.2 (68.7-71.6) in the training set and 70.2 (68.7-71.5) in the validation set. Moreover, DCA showed that our proposed model resulted in higher net benefits within a defined range of risk thresholds. The cumulative incidence rate of SPMT differed among risk groups, classified according to nomogram risk scores. CONCLUSION: The competing risk nomogram developed in this study exhibits high performance in predicting the occurrence of SPMT in patients with DTC. These findings may help clinicians identify patients at distinct levels of risk of SPMT and develop corresponding clinical management strategies.


Assuntos
Adenocarcinoma , Segunda Neoplasia Primária , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Pesquisa , Área Sob a Curva , Nomogramas , Programa de SEER
7.
ACS Appl Mater Interfaces ; 15(18): 22762-22776, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37105683

RESUMO

Traditional conductive fabrics are prepared by the synthesis of conductive polymers and the coating modification of metals or carbon black conductive materials. However, the conductive fabrics cause a significant decline in performance after washing or mechanical wear, which limits their application. Moreover, the single function of the traditional conductive fabric is also the reason that limits its wide application. In order to prepare a wearable, stable, high-performance, washable, multifunctional conductive fabric, we have carried out related research. In this work, polydopamine was used as a bonding layer, an adsorption reduction layer, and a protective layer to improve the bonding between silver nanoparticles and carbon nanotubes (CNTs) on the polyester fabric surface so as to prepare a multifunctional conductive fabric with a high-stability "sandwich" structure, in which a Ag-NPS@CNT structure acting as an intermediate conductive layer formed on the inner layer PDA@CNT by electroless silver plating and the outermost layer PDA@CNT coated on the surface of the intermediate conductive layer by the impregnation-drying method. The sheet resistance of an E-Fabric can reach 2.11 Ω/□ due to the uniform and dense conductive path formed by the special structure Ag-NPs@CNT. At a low voltage of 1.5 V, the E-Fabric can reach 117 °C in 50 s and remain stable. The electrical conductivity and current heating properties of the E-Fabric remain good even after multiple washing or bending tests. Due to its stable and outstanding electrical conductivity, the E-Fabric has an electromagnetic shielding efficiency (SET) of 35.3 dB in the X-band (8.2-12.4 GHz). In addition, E-Fabric-based spin-coated poly(methyl methacrylate) or polydimethylsiloxane electrodes exhibit excellent performance in nanogenerators. Through the low-frequency friction of the human body, transient voltages up to 4 V can be generated from a 2 cm × 2 cm electrode sample. The output power of a single generator can reach about 12 nW/cm2. Therefore, an E-Fabric is considered to have great potential in the fields of electric heating, electromagnetic shielding, and smart wearable devices.

8.
Mol Med Rep ; 24(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34184083

RESUMO

M2­like tumour­associated macrophages (TAMs) have been demonstrated to promote the growth of anaplastic thyroid carcinoma (ATC). However, the underlying mechanism of M2­like TAMs in ATC remains unclear. Thus, in the present study, the role and mechanism of M2­like TAMs in ATC were investigated. M2­like TAMs were induced by treatment with PMA, plus IL­4 and IL­13, and identified by flow cytometry. Transwell and sphere formation assays were applied to assess the invasion and stemness of ATC cells. The expression levels of insulin­like growth factor (IGF)­1 and IGF­2 were examined by ELISA and reverse transcription­quantitative PCR. Proteins related to the epithelial­mesenchymal transition (EMT), stemness and the PI3K/AKT/mTOR pathway were examined via western blotting. Immunohistochemistry (IHC) was used to detect the expression of the M2­like TAM markers CD68 and CD206 in ATC tissues and thyroid adenoma tissues. It was found that treatment with PMA plus IL­4 and IL­13 successfully induced M2­like TAMs. Following co­culture with M2­like TAMs, the invasive ability and stemness of ATC cells were significantly increased. The expression levels of the EMT­related markers N­cadherin and Vimentin, the stemness­related markers Oct4, Sox2 and CD133, and the insulin receptor (IR)­A/IGF1 receptor (IGF1R) were markedly upregulated, whereas E­cadherin expression was significantly decreased. In addition, the production of IGF­1 and IGF­2 was significantly increased. Of note, exogenous IGF­1/IGF­2 promoted the invasion and stemness of C643 cells, whereas blocking IGF­1 and IGF­2 inhibited metastasis and stemness by repressing IR­A/IGF­1R­mediated PI3K/AKT/mTOR signalling in the co­culture system. IHC results showed that the expression of CD68 and CD206 was obviously increased in ATC tissues. To conclude, M2­like TAMs accelerated the metastasis and increased the stemness of ATC cells, and the underlying mechanism may be related to the section of IGF by M2­like TAMs, which activates the IR­A/IGF1R­mediated PI3K/AKT/mTOR signalling pathway.


Assuntos
Células-Tronco Neoplásicas , Transdução de Sinais , Somatomedinas/metabolismo , Carcinoma Anaplásico da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Macrófagos Associados a Tumor/metabolismo , Adulto , Idoso , Anticorpos Neutralizantes/farmacologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Linhagem Celular , Cromonas/farmacologia , Feminino , Humanos , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like II/antagonistas & inibidores , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like II/farmacologia , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Morfolinas/farmacologia , Invasividade Neoplásica/imunologia , Metástase Neoplásica/imunologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Insulina/antagonistas & inibidores , Receptor de Insulina/metabolismo , Receptores Imunológicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Somatomedinas/genética , Serina-Treonina Quinases TOR/metabolismo , Carcinoma Anaplásico da Tireoide/imunologia , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
9.
J Phys Chem Lett ; 12(36): 8763-8769, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34491065

RESUMO

Metal halide perovskites have attracted great attention for their superior light energy conversion applications. Herein, we demonstrated a facile synthesis of zero-dimensional Sn2+ perovskite Cs4-xMxSnBr6(M = K+ and Rb+) material through the cation transformation reaction at room temperature. Cs4SnBr6 NCs was mixed with pure metal bromide salts (KBr and RbBr) via the mechanochemical process to successfully synthesize Cs4-xMxSnBr6 perovskite where transformation of Cs to mixed Cs/Rb and mixed Cs/K was achieved. By substituting different cations, the bright fluorescence of the Cs4-xMxSnBr6 was tuned from dim green to greenish-cyan while achieving the photoluminescence (PL) quantum yield of ∼39%. The crystal structure of Sn based perovskite with the substitution of K+ or Rb+ cations was determined by X-ray diffraction (XRD). Moreover, the Cs4-xMxSnBr6 demonstrated superior air stability and exhibited a better photocatalytic activity for CO2 reduction reaction (CO2RR) with high selectivity of CH4 gas with a higher yield rate compared to the pristine Cs4SnBr6 NCs.

10.
Life Sci ; 256: 117925, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32522570

RESUMO

AIMS: This study aims to explore the effect and underlying mechanism of zoledronic acid (ZA) on the incidence of thyroid cancer (TC) tumorigenesis. MATERIALS AND METHODS: Human mononuclear cells THP-1 were differentiated into M2-like tumor associated macrophages (TAMs) by incubation with PMA followed by additional incubation of IL-4 and IL-13. TC cells TPC-1 and IHH4 were co-cultured with M2-like TAMs. Identification of M2-like TAMs markers were determined by immunohistochemistry or flow cytometry. Cell proliferation, stemness and migration/invasion ability were measured by colony, sphere formation assay and transwell assay, respectively. The expression levels of cell stemness, EMT and Wnt/ß-catenin pathway-related factors were verified by qRT-PCR, Western blotting, and immunofluorescence. A subcutaneous tumor model was established in nude mice to examine the in vivo effects of ZA. KEY FINDINGS: M2-like TAMs were enriched in TC tissues, and they promoted the colony/sphere formation, accompanied with a down-regulated expression in E-cadherin and an up-regulated expression in N-cadherin, Vimentin and other stemness-associated markers (CD133, Oct4, c-Myc) in TC cells. The effects were suppressed when ZA co-treatment was given, because ZA inhibited the polarization of M2-like TAMs and ß-catenin entry into the nucleus. Moreover, in agreement with in vitro data, ZA also limited subcutaneous tumor formation and macrophage enrichment in nude mice. SIGNIFICANCE: ZA suppressed M2-like TAMs induced TC cell proliferation, stemness and metastasis through inhibiting M2-like TAMs polarization and Wnt/ß-catenin pathway, which sheds light on the mechanisms of TC and provides avenues for the development of clinical therapy to TC.


Assuntos
Macrófagos/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Ácido Zoledrônico/farmacologia , beta Catenina/metabolismo , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Carcinogênese/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Transdução de Sinais , Células THP-1/metabolismo , Microambiente Tumoral , Via de Sinalização Wnt
11.
Chin Med J (Engl) ; 121(17): 1633-7, 2008 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-19024089

RESUMO

BACKGROUND: Electroencephalogram (EEG) activity in normal subjects and epileptic patients is often closely related to the eye's status such as eye opened (EO), eye closure (ECL) and eyes closed (EC). ECL is the period immediately after closing of the eyes and only lasts for less than 3 seconds if the eyes remain closed. EC is the period as long as the eyes are closed. Epileptiform changes on EEG induced by ECL or EC are called the changes of ECL sensitivity (ECLS) or EC sensitivity (ECS). ECLS occurs mainly but not exclusively in photosensitive patients and ECS has been seen rarely in photosensitive patients. This study aimed to investigate the relationships among ECLS, ECS, photosensitivity and epilepsy syndromes in children. METHODS: EEG records from child patients in the EEG Department of Peking University First Hospital during the period of May 2005 to May 2007 were examined for the presence of ECLS or ECS. Open-close eye tests and intermittent photic stimulations were carried out during video-EEG monitoring for examining ECLS, ECS and photosensitivity. RESULTS: Based on ECLS and ECS on their EEGs, 30 patients were divided into ECLS group (16 cases) and ECS group (14 cases). There were more boys than girls in the two groups. The mean age of initial detection of ECLS and ECS was 10 years, and the average onset age of seizures was 9 years. The epilepsy syndromes in the ECLS group included idiopathic photosensitive occipital lobe epilepsy, Panayiotopoulos syndrome, symptomatic occipital lobe epilepsy, juvenile myoclonic epilepsy, juvenile absence epilepsy, eyelid myoclonia with absences, epilepsy with grand mal on awakening and pure photosensitive epilepsy with mainly generalized tonic clonic seizures. Those in the ECS group were juvenile myoclonic epilepsy, idiopathic photosensitive occipital lobe epilepsy, Panayiotopoulos syndrome and Gastaut type-idiopathic children occipital epilepsy. Photosensitivity was detected in 88% of patients with ECLS and 29% of patients with ECS. CONCLUSIONS: ECLS and ECS are relatively common in females. Comparing with ECS, ECLS is found in more epilepsy syndromes. However, ECS and ECLS could exist in the same epilepsy syndrome. ECLS and ECS can be associated or dissociated with photosensitivity. The rate of ECLS with photosensitivity is higher than that of ECS with photosensitivity, suggesting that mechanisms for ECLS, ECS and photosensitivity may be different but correlated.


Assuntos
Epilepsia/fisiopatologia , Fenômenos Fisiológicos Oculares , Estimulação Luminosa , Adolescente , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Masculino
12.
World J Pediatr ; 14(3): 290-297, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29700769

RESUMO

BACKGROUND: Infantile spasms (IS) was an epileptic disease with varied treatment widely among clinicians. Here, we aimed to compare and analyze the clinical characteristics of IS response to pyridoxine or topiramate monotherapy (TPM control IS). METHODS: The clinical manifestations, treatment processes and outcomes were analyzed in 11 pyridoxine responsive IS and 17 TPM-control IS. RESULTS: Of the 11 patients with pyridoxine responsive IS, nine were cryptogenic/idiopathic. Age of seizure onset was 5.36 ± 1.48 months. Spasms were controlled within a week in most of the patients. At the last follow-up, EEG returned to normal in 8. Psychomotor development was normal in 6, mild delay in 3, severe delay in 2. Of the 17 patients with TPM-control IS, 10 were cryptogenic/idiopathic. The age of seizure onset was 5.58 ± 2.09 months. All patients were controlled within a month. At the last follow-up, EEG was normal in 10. Psychomotor development was normal in 8, mild delay in 5, severe delay in 4. Genetic analysis did not show any meaningful results. CONCLUSIONS: The clinical characteristics and disease courses of pyridoxine responsive IS and TPM-control IS were similar, which possibly clued for a same pathogenic mechanism. Pyridoxine should be tried first in all IS patients, even in symptomatic cases. If patients were not responsive to pyridoxine, TPM could be tried.


Assuntos
Anticonvulsivantes/uso terapêutico , Frutose/análogos & derivados , Piridoxina/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Distribuição de Qui-Quadrado , Pré-Escolar , China , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Eletroencefalografia/métodos , Feminino , Seguimentos , Frutose/efeitos adversos , Frutose/uso terapêutico , Humanos , Lactente , Masculino , Piridoxina/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Espasmos Infantis/diagnóstico , Estatísticas não Paramétricas , Fatores de Tempo , Topiramato , Resultado do Tratamento
13.
Life Sci ; 78(25): 2944-52, 2006 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-16380138

RESUMO

Febrile seizure (FS) is a frequently encountered seizure type in childhood. Changes of brain function following FS have clinical importance. The recently identified gamma-aminobutyric acid B receptor (GABA(B)R) is a metabotropic receptor of GABA. In this study, we used a rat model of recurrent FS to investigate the changes of GABA(B)R1a and GABA(B)R2 subunits in hippocampus after recurrent FS by using Western blot, quantitative RT-PCR, double immunofluorescence, in situ hybridization and immunoprecipitation/Western blot. After treatment of hyperthermia and the presence of induced seizures once every 2 days for 10 times, GABA(B)R1a and GABA(B)R2 subunits in hippocampus were decreased after 24 h of the last treatment. The decrease of GABA(B)R1a lasted for 15 days but that of GABA(B)R2 persisted for more than 30 days. The binding of GABA(B)R1a to GABA(B)R2 in hippocampus was also decreased significantly after 24 h of the last treatment and lasted for more than 30 days. In situ hybridization showed that GABA(B)R1a mRNA was significantly decreased in dentate gyrus, and GABA(B)R2 mRNA was considerably reduced in CA3 region. In H10 and FS1 groups in which hyperthermia treatment was the same but no (H10 group) or only one seizure (FS(1) group) was induced, the decrease of GABA(B)R1a and GABA(B)R2 subunits and the reduced binding capability between GABA(B)R1a and GABA(B)R2 subunits were also detected but with less severity, and the time recovering from these abnormalities was shorter. We conclude that GABA(B)R1a and GABA(B)R2 subunits and the binding of the 2 subunits decrease in hippocampus for a relatively long period of time after recurrent FS in immature rats. These changes may result in long-lasting imbalance of excitation/inhibition function in hippocampus, and are derived from the consequences of recurrent febrile seizures.


Assuntos
Hipocampo/metabolismo , Subunidades Proteicas/metabolismo , Receptores de GABA-B/metabolismo , Convulsões Febris/metabolismo , Animais , Animais Recém-Nascidos , Western Blotting , Modelos Animais de Doenças , Masculino , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Chin Med J (Engl) ; 119(3): 191-6, 2006 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-16537003

RESUMO

BACKGROUND: Febrile seizure (FS) is the most common seizure disorders. Approximately one third of children with a febrile seizure have recurrent events. The mechanism of FS remains unclear. Heme oxygenase-1 (HO-1) is a member of the heat shock proteins family and can be induced in the brain by various stresses, including hyperthemia and seizure. This study aimed at investigating the changes of HO-1 in the cortex of rats after recurrent FS. METHODS: FS in rats was induced ten times, once every 2 days. In a bath of warm water, developing rats were randomly divided into two groups: control group (n = 16) and warm water-treated group (n = 50). The latter group was subdivided into hyperthermia group (n = 19) and FS group (n = 23). The expression and content of HO-1 mRNA in cortex were observed using in situ hybridization and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The content of HO-1 protein in cortex was measured using Western blotting. RESULTS: HO-1 mRNA expression of cortex neurons in FS group was markedly increased in comparison with those in hyperthermia and control groups (P = 0.00), however, there was no statistic difference between hyperthermia group and control group (P = 0.16). The relative amount of HO-1 mRNA in cortex in FS group was increased by 53.13% and 96% in comparison with those in hyperthermia group and control group respectively (P = 0.00), but there was no obvious difference between the later two groups (P = 0.051). Western blotting analysis showed that the HO-1 protein content in cortex in FS group was increased by 198% and 246% in comparison with those in hyperthermia group and control group respectively (P = 0.00). There was no obvious difference in HO-1 protein content between the later two groups (P = 0.09). CONCLUSIONS: Recurrent FS in rats can cause the increase of HO-1 mRNA and protein in cortex which may be involved in the mechanism of FS. The short-time recurrent hyperthermia can not induce the increase of HO-1 mRNA and protein.


Assuntos
Córtex Cerebral/enzimologia , Febre/enzimologia , Heme Oxigenase-1/genética , Convulsões Febris/enzimologia , Animais , Heme Oxigenase-1/análise , Masculino , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Recidiva
15.
Beijing Da Xue Xue Bao Yi Xue Ban ; 38(2): 132-4, 2006 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-16617352

RESUMO

OBJECTIVE: To explore the effect of gamma-aminobutyric acid B receptor (GABA(B)R)on nitric oxide (NO)/nitric oxide synthase (NOS) system during recurrent febrile seizures (FS). METHODS: Sprague-Dawley rats aged 21 days were randomly divided into four groups:control group, FS group, FS + baclofen group, FS + phaclofen group. FS in rats were induced ten times in a bath of warm water,once every 2 days. The plasma level of NO was detected by the spectrophotometer; the expression of nNOS mRNA was examined by in situ hybridization; the expression of nNOS protein was observed by immunohistochemistry. RESULTS: Compared with those in FS group,the plasma level of NO decreased [(19.02+/-9.31) micromol/L vs (40.03+/-9.12)micromol/L], and the expression of nNOS was down-regulated in FS + baclofen group; the plasma level of NO increased [(66.46+/-8.15) micromol/L vs (40.03+/-9.12) micromol/L] and the expression of nNOS was up-regulated in FS + phaclofen group. CONCLUSION: GABA(B)R modulated the expression of NO/NOS system during recurrent FS.


Assuntos
Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/sangue , Receptores de GABA-B/metabolismo , Convulsões Febris/metabolismo , Animais , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 8(3): 231-4, 2006 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-16787598

RESUMO

OBJECTIVE: Febrile seizure (FS) is the most common type of seizure disorders in children. Recurrent FS can cause hippocampal neurons injury. At the same time heme oxygenase/carbon monoxide (HO/CO) system and nitric oxide synthase/nitric oxide (NOS/NO) system were up-regulated and interacted each other. This study examined the effects of the two systems on the apoptosis of hippocampal neurons in rats with recurrent FS. METHODS: FS was induced in rats by exposure to warm water bath (45.2 degrees C), once every 2 days, 10 times in all. Sprague-Dawley (SD) rats aged 21 days were randomly assigned into four groups: Control (37 degrees C water bath exposure), FS, FS + ZnPP-IX (HO inhibitor) and FS + L-NAME (NOS inhibitor) groups. The apoptosis of hippocampal CA1 neurons was detected by TUNEL. RESULTS: After recurrent FS, the apoptotic cells in the hippocampal CA1 neurons increased by 225% compared with those in the Control group (P < 0.01). The apoptotic cells in the FS+ZnPP-IX group increased by 62% and 425% compared with those in the FS and the Control groups (both P < 0.01). The apoptotic cells in the FS + L-NAME group decreased by 38% compared with those in the FS group (P < 0.01) and increased by 100% compared with those in the Control group (P < 0.05). CONCLUSIONS: In recurrent FS, exogenous administration of HO inhibitor ZnPP-IX may induce an increase of apoptotic cells in hippocampal neurons, while NOS inhibitor L-NAME may decrease the apoptotic cells. The results suggest that the HO/CO system might alleviate neuronal damage, while NOS/NO system might augment neuronal damage.


Assuntos
Apoptose/efeitos dos fármacos , Monóxido de Carbono/farmacologia , Hipocampo/patologia , Óxido Nítrico/farmacologia , Convulsões Febris/patologia , Animais , Heme Oxigenase (Desciclizante)/fisiologia , Marcação In Situ das Extremidades Cortadas , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/fisiologia , Ratos , Ratos Sprague-Dawley , Convulsões Febris/tratamento farmacológico
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 8(2): 141-3, 2006 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-16613710

RESUMO

OBJECTIVE: Febrile seizure (FS) is one of the most common seizure types in children. Our previous studies have demonstrated that both gamma-aminobutyric acid B receptor (GABABR) and hydrogen sulfide (H2S) are involved in the pathogenesis of FS. This study was designed to explore the effect of GABABR on H2S/cystathionine-beta-synthase (CBS) system in recurrent FS. METHODS: Sixty-four Sprague-Dawley rats aged 21 days were randomly assigned into four groups: Control (37 degrees C water bath exposure), FS, FS+baclofen (GABABR excitomotor), and FS+phaclofen (GABABR inhibitor) groups (n=16 each). FS was induced by warm water bath exposure (45.2 degrees C, once every 2 days, 10 times in total. The plasma level of H2S was detected by the spectrophotometer. The expression of CBS mRNA was examined by in situ hybridization. The expressions of CBS protein was observed by immunohistochemistry. RESULTS: The plasma level of H2S increased in the FS+baclofen group (427.45 +/- 15.91 micromol/L) but decreased in the FS+phaclofen group (189.72 +/- 21.53 micromol/L) compared with that in the FS group (362.14 +/- 19.71 micromol/L). The expressions of CBS mRNA and protein were up-regulated in the FS+baclofen group but were down-regulated in the FS+phaclofen group compared with those in the FS group. CONCLUSIONS: GABABR modulated the expression of H2S/CBS system in recurrent FS.


Assuntos
Cistationina beta-Sintase/fisiologia , Sulfeto de Hidrogênio/metabolismo , Receptores de GABA-B/fisiologia , Convulsões Febris/metabolismo , Animais , Baclofeno/farmacologia , Cistationina beta-Sintase/genética , Sulfeto de Hidrogênio/sangue , Ratos , Ratos Sprague-Dawley , Recidiva
18.
Ying Yong Sheng Tai Xue Bao ; 27(12): 4029-4038, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29704364

RESUMO

Greenhouse pot trials were conducted to investigate the effects of arbuscular mycorrhizal fungus (Glomus mosseae, Glomus tortuosum, Glomus intraradices and Glomus etunicatum) inoculation on the seedling growth, occurance of Fusarium wilt, population of Fusarium oxysporum and rhizosphere microbial community functional diversity in faba bean rhizosphere soil. Results showed that after inoculation of G. mosseae, G. tortuosum, G. intraradices and G. etunicatum, the shoot and root fresh mass of faba bean seedlings increased significantly, the disease index of faba bean fusarium wilt decreased significantly by 94.0%, 60.0%, 64.0% and 94.0%, respectively, the amount of F. oxysporum of faba bean rhizosphere decreased significantly by 98.6%, 74.3%, 77.8% and 90.4%, respectively. The best inhibitory effects to Fusarium wilt were with G. mosseae and G. etunicatum treatments. Inoculation of G. mosseae, G. tortuosum and G. etunicatum significantly increased carbon sources utilization ability of carbohydrates, amino acids, carboxylic acids and phenolic acids, with the average well color development (AWCD) value being increased by 34.4%, 31.5% and 50.8% respectively, but such significant differences were not observed with inoculation of G. intraradice. Principal component analyses showed that inoculation of G. mosseae, G. tortuosum and G. etunicatum fungi changed the rhizospheric microbial community composition. Correlation analyses showed that the utilization of carbohydrates carbon sources (ß-Methyl-D-glucoside, D-Galacturonic acid, D-Mannitol, N-Acetyl-D-Glucosamine, D-Cellobiose,) and carboxylic acids carbon sources (D-Galactonic acid-γ-Lactone) were significantly increased after inoculation of G. tortuosum, and the utilization of L-Arginine and 4-Hydroxy benzoic acid significantly increased after inoculation of G. mosseae and G. etunicatum. Carbohydrates, carboxylic acids were main carbon sources utilized by rhizosphere microbes after G. tortuosum and G. intraradices inoculation, and amino acids and phenolic acids were main carbon sources utilized by rhizosphere microbes after G. mosseae and G. etunicatum inoculation. Inoculation of AM fungi significantly increased the activities of rhizosphere microbes, changed soil microbe community functional diversity, and thus inhibited the growth of F. oxysporum. The inhibitory impacts of AM fungi inoculations depended on the changes of microbes utilizing carbon sources.


Assuntos
Agentes de Controle Biológico , Fusarium/patogenicidade , Micorrizas/fisiologia , Doenças das Plantas/prevenção & controle , Rizosfera , Vicia faba/microbiologia , Glomeromycota/fisiologia , Doenças das Plantas/microbiologia , Raízes de Plantas , Microbiologia do Solo
19.
Ying Yong Sheng Tai Xue Bao ; 27(6): 1984-1992, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29737708

RESUMO

A field trial was conducted to investigate effects of wheat and faba bean intercropping on incidence and index of fusarium wilt, amount of Fusarium oxysporum of faba bean, oxidase activity and membrane peroxidation of faba bean roots. Functional diversity of microbial community in rhizosphere soil of faba bean was analyzed by using Biolog microbial analysis system, contents of pheno-lic acids in faba bean rhizosphere soil were determined with high performance liquid chromatography (HPLC). Results showed that in comparison with that of monocropped faba bean, wheat and faba bean intercropping tended to reduce the incidence and disease index of faba bean. The fusarium wilt was significantly decreased by 15.8% and 22.8% during the peak infection and late infection stages, and the average well color development (AWCD value) was promoted obviously. The Shannon diversity (H) and richness (S) increased by 4.4% and 19.4% during the peak infection stage and 5.3% and 37.1% during the late infection stage, respectively. Principal component analysis demonstrated that intercropping significantly changed the rhizospheric microbial community composition. The amount of F. oxysporum in rhizosphere soil of intercropped faba bean was significantly decreased by 53.8% and 33.1%, respectively, during the peak infection and late infection stages, and contents of 4-hydroxy benzoic acid, vanillic acid, syringic acid, ferulic acid, benzoic acid and cinnamic acid also significantly decreased, peroxidase (POD), catalases (CAT) activities in roots of intercropped faba bean increased significantly by 20.0% and 31.3%, respectively during the peak infection stage and 38.5% and 66.7% respectively during the late infection stage, and the malondialdehyd (MDA) content decreased significantly by 36.3% and 46.3%, respectively during peak infection stage and late infection stage. It was concluded that wheat with faba bean intercropping could significantly promote the soil microbial activity and diversity, reduce the accumulation of phenolic allelochemicals and the amount of F. oxysporum in rhizosphere soil, increase the activities of CAT and POD, reduce MDA content in roots, and thus promote the resistance of faba bean to F. oxysporum infection.


Assuntos
Agricultura/métodos , Fusarium , Doenças das Plantas/prevenção & controle , Microbiologia do Solo , Vicia faba/microbiologia , Raízes de Plantas , Rizosfera , Solo , Triticum
20.
Beijing Da Xue Xue Bao Yi Xue Ban ; 37(6): 579-81, 2005 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-16378105

RESUMO

OBJECTIVE: To study the alteration of hydrogen sulfide (H(2)S)/ cystathionine-beta-synthase (CBS) system during recurrent febrile seizures (FS) in the hippocampus of developing rats. METHODS: The rats were randomly divided into control group (n=8) and hyperthermia-treated group (n=22). Which was subdivided into FS group (n=8) and H group(no seizure occurred, n=9) according to whether seizures occurred. The plasma level of H(2)S was detected by the spectrophotometer. The expression levels of CBS gene and protein were examined by in situ hybridization and immunohistochemistry respectively. RESULTS: The plasma levels of H(2)S were increased significantly in FS group compared with those of control group or H group. The expression levels of CBS gene and protein were enhanced in FS group compared with those of control group or H group. CONCLUSION: The expression levels of H(2)S/ CBS system were up-regulated during recurrent FS.


Assuntos
Cistationina beta-Sintase/genética , Sulfeto de Hidrogênio/sangue , Convulsões Febris/fisiopatologia , Animais , Cistationina beta-Sintase/biossíntese , Feminino , Expressão Gênica , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Hipertermia Induzida , Imuno-Histoquímica , Hibridização In Situ , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Recidiva , Convulsões Febris/sangue , Convulsões Febris/genética , Espectrofotometria , Regulação para Cima
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