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1.
Zhongguo Zhong Yao Za Zhi ; 46(18): 4644-4653, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581072

RESUMO

To systematically review the efficacy and safety of acupuncture combined with minimally invasive surgery or basic the-rapy in treating hypertensive intracerebral hemorrhage(HICH) patients compared with minimally invasive surgery or basic treatment. In this study, the four Chinese databases, the four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, all above were systematically and comprehensively retrieved from the time of database establishment to September 10, 2020. Rando-mized controlled trials(RCTs) were screened out according to inclusion criteria and exclusion criteria established in advanced. The methodological quality of included studies was evaluated by the tool named "Cochrane bias risk assessment 6.1". Meta-analysis of the included studies was performed using RevMan 5.4, and the quality of outcome indicators was evaluated by the GRADE system. Finally, 17 studies were included, involving 1 852 patients with HICH, and the overall quality of the included studies was not high. According to Meta-analysis,(1)CSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-3.50,95%CI[-4.39,-2.61],P<0.000 01);(2)NIHSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.78,95%CI[-5.55,-4.00],P<0.000 01);(3)the cerebral hematoma volume of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.44,95%CI[-5.83,-3.04],P<0.000 01);(4)ADL score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=20.81,95%CI[17.25,24.37],P<0.000 01);(5)the GCS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=2.41,95%CI[1.90,2.91],P<0.000 01). The GRADE system showed an extremely low level of evidence for the above outcome indicators. Adverse reactions were mentioned only in two literatures, with no adverse reactions reported. The available evidence showed that acupuncture combined with minimally invasive surgery or basic therapy had a certain efficacy in patients of HICH compared with minimally invasive surgery or basic therapy. However, due to the high risk of bias in the included studies, its true efficacy needs to be verified by more high-quality studies in the future.


Assuntos
Terapia por Acupuntura , Hemorragia Intracraniana Hipertensiva , Humanos , Hemorragia Intracraniana Hipertensiva/terapia , Resultado do Tratamento
2.
Biochim Biophys Acta Gene Regul Mech ; 1864(11-12): 194751, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34500082

RESUMO

Transcription factors play a key role in maintaining cell identity. One mechanism of such cell memory after multiple rounds of cell division cycles is through persistent mitotic chromosome binding, although how individual transcription factors achieve mitotic chromosome retention is not completely understood. Here we show that PAX6, a lineage-determining transcription factor, coats mitotic chromosomes. Using deletion and point mutants associated with human ocular diseases in live-cell imaging analysis, we identified two regions, MCR-D1 and MCR-D2, that were responsible for mitotic chromosome retention of PAX6. We also identified three nuclear localization signals (NLSs) that contributed to mitotic chromosome retention independent of their nuclear import functions. Full mitotic chromosome retention required the presence of DNA-binding domains as well as NLSs within MCR-Ds. Furthermore, disease-associated mutations and NLS mutations changed the distribution of intrinsically disordered regions (IDRs) in PAX6. Our findings not only identify PAX6 as a novel mitotic chromosome retention factor but also demonstrate that the mechanism of mitotic chromosome retention involves sequence-specific DNA binding, NLSs, and molecular conformation determined by IDRs. These findings link mitotic chromosome retention with PAX6-related pathogenesis and imply similar mechanisms for other lineage-determining factors in the PAX family.

3.
Biochim Biophys Acta Mol Cell Res ; 1868(11): 119100, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34274396

RESUMO

Heterochromatin, a type of condensed DNA in eukaryotic cells, has two main categories: Constitutive heterochromatin, which contains H3K9 methylation, and facultative heterochromatin, which contains H3K27 methylation. Methylated H3K9 and H3K27 serve as docking sites for chromodomain-containing proteins that compact chromatin. M33 (also known as CBX2) is a chromodomain-containing protein that binds H3K27me3 and compacts chromatin in vitro. However, whether M33 mediates chromatin compaction in cellulo remains unknown. Here we show that M33 compacts chromatin into DAPI-intense heterochromatin domains in cells. The formation of these heterochromatin domains requires H3K27me3, which recruits M33 to form nuclear bodies. G9a and SUV39H1 are sequentially recruited into M33 nuclear bodies to create H3K9 methylated chromatin in a process that is independent of HP1α. Finally, M33 decreases progerin-induced nuclear envelope disruption caused by loss of heterochromatin. Our findings demonstrate that M33 mediates the formation of condensed chromatin by forming nuclear bodies containing both H3K27me3 and H3K9me3. Our model of M33-dependent chromatin condensation suggests H3K27 methylation corroborates with H3K9 methylation during the formation of facultative heterochromatin and provides the theoretical basis for developing novel therapies to treat heterochromatin-related diseases.

4.
Biosci Rep ; 41(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33300046

RESUMO

Wilson's disease (WD) is an autosomal recessive disease caused by mutation of the ATPase copper transporting ß (ATP7B) gene, resulting in abnormal copper metabolism. We aimed to investigate the protective effect of GanDouLing (GDL) on neural stem cell (NSC) function in a mouse model of WD. NSCs were treated with different concentrations of GDL alone or in combination with penicillamine, following which we evaluated cellular growth, apoptosis, and differentiation. Nuclear factor E2-related factor 2 (Nrf2) pathway and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation were analyzed via Western blotting. Treatment with GDL alone or in combination with penicillamine significantly increased proliferation and inhibited apoptosis of NSCs in a dose-dependent manner. In addition, GDL treatment remarkably promoted differentiation of NSCs. Consistently, levels of class III ß-tubulin (Tuj1) and microtubule-associated protein 2 (MAP2) were significantly elevated, whereas glial fibrillary acidic protein (GFAP) levels were obviously suppressed in the presence of GDL or penicillamine. In vivo assays confirmed that GDL increased the ratio of Ki67+, Tuj1+, and MAP2+ cells and suppressed apoptosis in the hippocampal region in WD mice. Behavioral assays revealed that both GDL and penicillamine improved memory ability in WD models. Mechanistically, GDL treatment led to activation of Nrf2 signaling and suppression of the NLRP3 inflammasome in WD mice. Notably, inhibition of Nrf2 signaling reversed the protective effects of GDL on hippocampal NSCs. Collectively, these findings demonstrate that GDL exerts a protective effect on NSCs and promotes neurogenesis by targeting Nrf2 signaling and the NLRP3 inflammasome in WD.

5.
Parkinsonism Relat Disord ; 80: 113-119, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32980772

RESUMO

BACKGROUND: Pain is common in Parkinson's disease, and there is no effective treatment. We conducted a clinical trial to determine whether high-frequency repetitive transcranial magnetic stimulation over the primary motor cortex alleviates musculoskeletal pain in patients with Parkinson's disease. METHODS: In this single-center and double-blind trial, 52 patients with Parkinson's disease and musculoskeletal pain were randomly allocated to 26-member groups receiving 5 sessions of either 20-Hz repetitive transcranial magnetic stimulation or sham stimulation over the primary motor cortex. The participants underwent assessments in the "ON" medication state at baseline, after the fifth session, and at 2- and 4-week follow-up timepoints. The primary outcomes were pain scores on a numeric rating scale. The secondary outcomes were scores on clinical scales assessing motor symptoms, depression, anxiety, autonomic symptoms, sleep quality, and the overall severity of Parkinson's disease. RESULTS: Analyses revealed significant group × time interactions for numeric rating scale pain scores (p < 0.001), motor symptom scores (p < 0.001), depression scores (p = 0.009), anxiety scores (p = 0.013), and overall disease severity scores (p < 0.001). Post hoc analyses confirmed that the repetitive transcranial magnetic stimulation group, but not the sham stimulation group, exhibited significant improvements in numeric rating scale pain scores, motor symptom scores, depression scores, anxiety scores, and overall disease severity scores. CONCLUSION: High-frequency repetitive transcranial magnetic stimulation over the primary motor cortex may be an effective adjunct therapy for alleviating musculoskeletal pain in patients with Parkinson's disease.

6.
Biosci Rep ; 40(8)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32809015

RESUMO

The clinical data of safety and efficacy of a combined treatment with dimercaptosuccinic acid (DMSA) and Zinc with 2 years' follow-up in 60 neurological Wilson's disease (WD) patients was retrospectively analyzed. All the patients included in the present study were newly diagnosed and initialized with D-penicillamine (DPA) treatment but were found to have either neurological deterioration or allergy, and their treatment was switched to a combined treatment of DMSA and Zinc. Fifty-one patients (85%) had the neurological symptoms improved 1 and 2 years after treatment, 7 (11.67%) experienced a stable neurological condition, and 2 (3.33%) suffered deterioration of neurological symptoms. No early neurological deterioration was observed in all patients. Twenty-five percent patients experienced mild adverse reactions which did not require a discontinuation of the DMSA and Zinc treatment. Our study confirmed the safety and efficacy of the combined DMSA and Zinc therapy as an initial and probably long-term treatment in neurological WD patients.


Assuntos
Encéfalo/efeitos dos fármacos , Quelantes/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/efeitos adversos , Succímero/uso terapêutico , Zinco/uso terapêutico , Adolescente , Adulto , Encéfalo/fisiopatologia , Criança , Progressão da Doença , Hipersensibilidade a Drogas/diagnóstico , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/fisiopatologia , Humanos , Masculino , Estudos Retrospectivos , Succímero/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem , Zinco/efeitos adversos
7.
Artigo em Inglês | MEDLINE | ID: mdl-33456485

RESUMO

Objective: Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods: Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results: Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion: Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.

8.
Medicine (Baltimore) ; 98(26): e15917, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261498

RESUMO

Acute onset neurological symptoms evoked by traumatic, surgical, or emotional events in Wilson disease (WD) have never been reported and its clinical characteristics are unclear.We aimed to summarize the clinical characteristics of a special WD whose neurological symptoms acutely developed after traumatic, surgical, or emotional events.Retrospective pilot study.Thirty-one patients who had acute onset neurological symptom as an initial presentation of WD or a new presentation of hepatic WD after mild trauma, surgery, or emotional events were retrospectively studied. All patients were followed for half to 1 year after regular anti-copper treatment.The averaged latency for neurological symptom presentation was 2.79 ±â€Š1.21 hours. The most frequent neurological symptoms were tremor (74%) and basal ganglia (BG) lesions were detected on magnetic resonance imaging in all patients. Lesions in other regions were much less frequently detected. Neurological symptom score and its recovery after treatment were correlated with lesion location: BG area and BG plus other brain areas. Neurological symptoms improved in 21 patients who received timely anti-copper treatment but continued to deteriorate in 6 patients who did not accept regular anti-copper treatment for delayed diagnosis.A diagnosis of WD should be considered when adolescents or adults experience acute presentation of extrapyramidal systems after traumatic, surgical, or emotional stimulation. Timely anti-copper therapy usually gives rise to an excellent prognosis.


Assuntos
Emoções , Degeneração Hepatolenticular/epidemiologia , Degeneração Hepatolenticular/fisiopatologia , Complicações Pós-Operatórias/epidemiologia , Estresse Psicológico/complicações , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Criança , Estudos Transversais , Feminino , Seguimentos , Degeneração Hepatolenticular/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudo de Prova de Conceito , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
9.
Curr Mol Med ; 19(5): 342-348, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873920

RESUMO

BACKGROUND: Liver kinase B1 (LKB1)/5'-adenosine monophosphate-activated protein kinase (AMPK) signaling, a metabolic checkpoint, plays a neuro-protective role in the pathogenesis of Alzheimer's disease (AD). Amyloid-ß (Aß) acts as a classical biomarker of AD. The aim of the present study was to explore whether berberine (BBR) activates LKB1/AMPK signaling and ameliorates Aß pathology. METHODS: The Aß levels were detected using enzyme-linked immunosorbent assay and immunohistochemistry. The following biomarkers were measured by Western blotting: phosphorylated (p-) LKB1 (Ser334 and Thr189), p-AMPK (AMPKα and AMPKß1), synaptophysin, post-synaptic density protein 95 and p-cAMP-response element binding protein (p-CREB). The glial fibrillary acidic protein (GFAP) was determined using Western blotting and immunohistochemistry. RESULTS: BBR inhibited Aß expression in the brain of APP/PS1 mice. There was a strong up-regulation of both p-LKB1 (Ser334 and Thr189) and p-AMPK (AMPKα and AMPKß1) in the brains of APP/PS1 transgenic mice after BBR-treatment (P<0.01). BBR promoted the expression of synaptophysin, post-synaptic density protein 95 and p-CREB(Ser133) in the AD brain, compared with the model mice. CONCLUSION: BBR alleviates Aß pathogenesis and rescues synapse damage via activating LKB1/AMPK signaling in the brain of APP/PS1 transgenic mice.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Peptídeos beta-Amiloides/metabolismo , Berberina/farmacologia , Encéfalo/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Animais , Encéfalo/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Transgênicos , Transdução de Sinais/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Sinapses/genética , Sinapses/metabolismo
10.
Biosci Rep ; 39(3)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30804230

RESUMO

Purpose: Wilson's disease (WD) is a genetic disorder of copper metabolism with pathological copper accumulation in the brain. The purpose of the present study was to evaluate the relationship between the damaged white matter and the impaired cognitive function in WD patients. Materials and methods: Thirty WD adolescents and thirty age- and sex-matched healthy controls (HC) were enrolled. All subjects had received brain MRI, including conventional and diffusion-tensor imaging (DTI) scans. The DTI parameter of fractional anisotropy (FA) was calculated by diffusion kurtosis estimator software. The t test was used to compare the differences between two groups. The correlation between cognitive function and whiter matter disorders were analyzed by linear regression. The results of FA parameter and MD parameter intergroup analysis were both corrected with False Discovery Rate (FDR) simulations by SPSS. Results: WD adolescents showed significantly lower scores of time-based prospective memory (TBPM) and verbal fluency test (VFT) compared with HC. We found significantly higher FA in the right thalamus, right lentiform nucleus, left thalamus, left lentiform nucleus, and brain stem in WD adolescents. Besides, WD adolescents exhibited significantly lower FA in right cerebellum and cingulum and left middle frontal lobe compared with controls (P<0.05). There were significantly negative correlations between FA in bilateral lentiform and thalamus and cognitive impairment in WD adolescents (P<0.05). Conclusion: The whiter matter of WD adolescents was impaired and mainly distributed in subcortical brain regions. The impaired cognitive function was affected by the damaged whiter matter. The present study may be helpful for recognition and understanding of WD.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Degeneração Hepatolenticular/fisiopatologia , Substância Branca/fisiopatologia , Adolescente , Anisotropia , Encéfalo/patologia , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Feminino , Degeneração Hepatolenticular/diagnóstico por imagem , Degeneração Hepatolenticular/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
11.
J Invest Surg ; 31(2): 75-81, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28135891

RESUMO

AIM: Hypersplenism can occur in patients with Wilson's disease (WD). Surgical splenectomy is a conventional treatment for this condition; however, emotional and neurological deterioration may follow splenectomy. In recent years, partial splenic embolization (PSE) has been increasingly performed as a nonsurgical alternative treatment for hypersplenism. The aim of this study was to evaluate the effectiveness and safety of PSE compared with splenectomy in the treatment of hypersplenism in WD patients. METHODS: Fifty WD patients with hypersplenism were randomly divided into two groups (group A and group B), each including 25 patients. Patients in groups A and B were treated with PSE and splenectomy, respectively. Data were collected on the clinical efficacy of each procedure, adverse reactions, hematologic and blood chemistry test results, and abdominal computed tomography (CT) scan findings (group A only). RESULTS: Marked improvements in the platelet and leukocyte counts after PSE and splenectomy were observed in all patients. PSE was associated with improved liver function without severe complications, and no significant changes in emotional and neurological symptoms were observed. In contrast, seven WD patients suffered neurological deterioration after splenectomy. CONCLUSIONS: Hypersplenism in WD patients was successfully treated by PSE, which appears to be a safe and effective alternative treatment for WD-induced hypersplenism.


Assuntos
Terapias Complementares/métodos , Embolização Terapêutica/métodos , Degeneração Hepatolenticular/complicações , Hiperesplenismo/terapia , Adolescente , Adulto , Cateteres , Embolização Terapêutica/instrumentação , Feminino , Humanos , Hiperesplenismo/sangue , Hiperesplenismo/etiologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Baço/fisiopatologia , Baço/cirurgia , Esplenectomia , Resultado do Tratamento , Adulto Jovem
12.
Zhen Ci Yan Jiu ; 42(6): 510-3, 2017 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-29318857

RESUMO

OBJECTIVE: To explore the analgesic effect of electroacupuncture(EA)by modulating 5-hydroxytryptamine 7 (5-HT7) receptor in periaqueductal gray (PAG) and plasma calcitonin gene-related peptide (CGRP). METHODS: Forty-two male Sprague Dawley (SD) rats were randomly divided into control,model and EA groups, 14 rat in each one. The neurogenic migraine model was established by repeated electrical stimulation on sagittal sinus duramater. Intracranial electrodes were used in the control group without stimuli. The rats in the EA group received EA (0.5-1 mA, 2 Hz/15 Hz) at "Fengchi" (GB 20) for 10 min after dural electrical stimulation, once a day for 6 days. The expression of 5-HT7 receptor in the PAG was assessed by immunofluorescence and Western blot, respectively; plasma CGRP was measured by radioimmunoassay. RESULTS: Compared with the control group, the positive neuron number and protein expression of 5-HT7 receptor in PAG and plasma CGRP increased after model establishment (all P<0.001). The above mentioned indexes were reversed in the EA group compared with those in the model group (the positive neuron number and protein expression of 5-HT7 receptor, P<0.01; plasma CGRP, P<0.05). CONCLUSIONS: EA at GB 20 can down-regulate the expression of 5-HT7 receptor in the PAG and reduce the content of plasma CGRP in the rats of migraine.


Assuntos
Eletroacupuntura , Transtornos de Enxaqueca , Pontos de Acupuntura , Animais , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina , Masculino , Substância Cinzenta Periaquedutal , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina
13.
Sci Rep ; 6: 26509, 2016 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-27211601

RESUMO

Promyelocytic leukemia nuclear bodies (PML-NBs) are PML-based nuclear structures that regulate various cellular processes. SUMOylation, the process of covalently conjugating small ubiquitin-like modifiers (SUMOs), is required for both the formation and the disruption of PML-NBs. However, detailed mechanisms of how SUMOylation regulates these processes remain unknown. Here we report that SUMO5, a novel SUMO variant, mediates the growth and disruption of PML-NBs. PolySUMO5 conjugation of PML at lysine 160 facilitates recruitment of PML-NB components, which enlarges PML-NBs. SUMO5 also increases polySUMO2/3 conjugation of PML, resulting in RNF4-mediated disruption of PML-NBs. The acute promyelocytic leukemia oncoprotein PML-RARα blocks SUMO5 conjugation of PML, causing cytoplasmic displacement of PML and disruption of PML-NBs. Our work not only identifies a new member of the SUMO family but also reveals the mechanistic basis of the PML-NB life cycle in human cells.


Assuntos
Núcleo Celular/metabolismo , Lisina/metabolismo , Proteína da Leucemia Promielocítica/genética , Proteína da Leucemia Promielocítica/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Animais , Linhagem Celular Tumoral , Núcleo Celular/genética , Clonagem Molecular , Regulação da Expressão Gênica , Células HEK293 , Células HeLa , Humanos , Células K562 , Células MCF-7 , Camundongos , Células NIH 3T3 , Proteínas Nucleares/metabolismo , Especificidade de Órgãos , Proteína da Leucemia Promielocítica/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Sumoilação , Fatores de Transcrição/metabolismo , Ubiquitinas/metabolismo
14.
Brain Res Bull ; 124: 269-77, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27233782

RESUMO

Diabetic conditions worsen the prognosis of stroke. The molecular mechanism underlying the impairment of post-stroke recovery is not very clear. Here, we establish a rat model resembling human cerebral infarction with or without diabetes to determine how diabetes impairs cognitive recovery. Our data show that diabetes inhibits hippocampal BDNF expression and impairs the survival and differentiation of the newborn neural cells in rats with ischemia. Consequently, the rats of diabetic ischemia have a significantly lower score in spatial learning and memory in the Morris water maze test than the non-diabetic ischemia model rats. On the other hand, treatment with BDNF effectively improves hippocampal neurogenesis and the spatial learning and memory in rat with diabetic ischemia. All together, our data suggest that diabetes impaired spatial learning and memory and hippocampal neurogenesis in rats with ischemia by inhibition of the BDNF expression in the hippocampus.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diabetes Mellitus Experimental/complicações , Hipocampo/fisiologia , Ataque Isquêmico Transitório/complicações , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Neurogênese/fisiologia , Aprendizagem Espacial/fisiologia , Animais , Antibióticos Antineoplásicos/toxicidade , Fator Neurotrófico Derivado do Encéfalo/administração & dosagem , Bromodesoxiuridina , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Sprague-Dawley , Aprendizagem Espacial/efeitos dos fármacos , Estreptozocina/toxicidade , Regulação para Cima/efeitos dos fármacos
15.
J Biol Chem ; 290(33): 20556-64, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26149688

RESUMO

PAX3 is a transcription factor critical to gene regulation in mammalian development. Mutations in PAX3 are associated with Waardenburg syndrome (WS), but the mechanism of how mutant PAX3 proteins cause WS remains unclear. Here, we found that PAX3 loads on mitotic chromosomes using its homeodomain. PAX3 WS mutants with mutations in homeodomain lose the ability to bind mitotic chromosomes. Moreover, loading of PAX3 on mitotic chromosomes requires arginine methylation, which is regulated by methyltransferase PRMT5 and demethylase JMJD6. Mutant PAX3 proteins that lose mitotic chromosome localization block cell proliferation and normal development of zebrafish. These results reveal the molecular mechanism of PAX3s loading on mitotic chromosomes and the importance of this localization pattern in normal development. Our findings suggest that PAX3 WS mutants interfere with the normal functions of PAX3 in a dominant negative manner, which is important to the understanding of the pathogenesis of Waardenburg syndrome.


Assuntos
Arginina/metabolismo , Cromossomos Humanos , Mitose/genética , Fatores de Transcrição Box Pareados/genética , Síndrome de Waardenburg/genética , Animais , Células HEK293 , Humanos , Larva/metabolismo , Metilação , Fator de Transcrição PAX3 , Proteína-Arginina N-Metiltransferases/metabolismo , Peixe-Zebra/crescimento & desenvolvimento
16.
PLoS One ; 10(4): e0124569, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25910248

RESUMO

Splenomegaly and pancytopenia are common in Wilson's disease (WD) and splenectomy is one of the conventional treatments for splenomegaly and the associated pancytopenia. However, splenectomy remained controversial for hypersplenism in WD as it was reported that splenectomy leaded to serious emotional and neurological deterioration in WD patients with hypersplenism. In the current study, we present our experiences in 70 WD patients with hypersplenism who had undergone splenectomy, outlining the safety and efficacy of splenectomy in WD. The clinical database of 70 WD patients with hypersplenism who had undergone splenectomy in our hospital between 2009 and 2013 were reviewed and followed-up regularly. Before splenectomy, all the patients accepted a short period of anti-copper treatment with intravenous sodium 2, 3-dimercapto-1-propane sulfonate (DMPS). All the patients demonstrated a marked improvement in platelet and leucocyte counts after splenectomy. No severe postoperative complication was observed. In particular, none of the 37 patients with mixed neurologic and hepatic presentations experienced neurological deterioration after splenectomy, and none of the patients with only hepatic presentations newly developed neurological symptoms. During the one year follow-up period, no patient presented hepatic failure or hepatic encephalopathy, no hepatic patient newly developed neurological presentations, and only 3 patients with mixed neurologic and hepatic presentations suffered neurological deterioration and these 3 patients had poor compliance of anti-copper treatment. Quantative analysis of the neurological symptoms in the 37 patients using the Unified Wilson's Disease Rating Scale (UWDRS) showed that the neurological symptoms were not changed in a short-term of one week after splenectomy but significantly improved in a long-term of one year after splenectomy. Additionally, compared to that before splenectomy, the esophageal gastric varices in most patients significantly improved one year after splenectomy. Thus, we may conclude that splenectomy is a safe and effective therapeutic measure for hypersplenism in WD patients who had been preoperatively treated with DMPS for powerful anti-copper therapy.


Assuntos
Degeneração Hepatolenticular/patologia , Degeneração Hepatolenticular/cirurgia , Hiperesplenismo/patologia , Esplenectomia , Adolescente , Adulto , Contagem de Células Sanguíneas , Criança , China , Terapia Combinada , Cobre/sangue , Feminino , Degeneração Hepatolenticular/sangue , Degeneração Hepatolenticular/terapia , Humanos , Testes de Função Hepática , Masculino , Esplenectomia/efeitos adversos , Esplenomegalia/patologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
Anticancer Res ; 34(9): 4717-22, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25202049

RESUMO

BACKGROUND: Proper re-establishment of heterochromatin after each round of DNA replication is critical to the preservation of cell identity. Paired box 3 (PAX3), a transcription factor important in embryonic development, was found to mediate the formation of pericentromeric heterochromatin. However, how PAX3 recognizes the heterochromatic environment and re-establishes it after DNA replication remains unclear. MATERIALS AND METHODS: Cell-cycle synchronization, fluorescence microscopic analyses, and co-immunoprecipitation were used to analyze the heterochromatic localization of PAX3 in HEK 293 cells and NIH 3T3 cells. RESULTS: We found that PAX3 binds pericentromeric heterochromatin during middle-to-late S phase. Loading of PAX3 onto pericentromeric heterochromatin requires poly(ADP-ribose) polymerase 1 (PARP1). Furthermore, loss of PAX3 or PARP1 delays cell-cycle progression through the S phase. CONCLUSION: Our results reveal how PAX3 recognizes and maintains pericentromeric heterochromatin at the S phase of the cell cycle.


Assuntos
Heterocromatina/metabolismo , Fatores de Transcrição Box Pareados/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Fase S , Animais , Ciclo Celular , Células HEK293 , Heterocromatina/genética , Humanos , Camundongos , Células NIH 3T3 , Fatores de Transcrição Box Pareados/genética , Ligação Proteica , Transporte Proteico , Proteínas Recombinantes de Fusão/metabolismo
18.
Biochim Biophys Acta ; 1839(7): 579-91, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24852358

RESUMO

Aberrant expression levels of transcriptional regulators result in alterations in transcriptional control. STAF65γ is a structural subunit of the GCN5 transcriptional co-activator complex. Reports showed that STAF65γ is highly expressed in several human cancer cells, but the consequences of this aberrant expression pattern remain elusive. Here, we show that the STAF65γ protein is highly expressed in lung adenocarcinoma patients and high levels of STAF65γ correlate with poor prognosis. High levels of STAF65γ cause repression of the c-Myc oncogene through physical association with transcription factor YY1 and co-repressors HDACs. Physical interactions between STAF65γ and class IIa HDACs facilitate nuclear enrichment and regulate the assembly of HDAC complexes. Moreover, SUMOylation of STAF65γ is necessary for maintaining the co-repressor complex containing YY1 and class IIa HDACs at the promoter. Our findings reveal a distinct role of STAF65γ in nuclear import, transcriptional repression, and cell cycle regulation at high levels of expression, which is associated with poor clinical outcomes of lung adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Histona Desacetilases/genética , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas , Transativadores/genética , Transcrição Genética , Transporte Ativo do Núcleo Celular/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Ciclo Celular/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Repressoras/genética , Sumoilação , Fator de Transcrição YY1/genética
19.
PLoS One ; 8(8): e73033, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23991171

RESUMO

ZBRK1, a zinc finger protein that interacts with breast cancer 1 (BRCA1) and KRAB-ZFP-associated protein 1 (KAP1), has been suggested to serve as a tumor suppressor via repression of tumor metastasis/invasion. To date, the detailed molecular mechanisms for how BRCA1 and KAP1 participate in ZBRK1-mediated transcriptional repression, metastasis and invasion as well as the associated clinical relevance remain unclear. In this study, we demonstrated that both the N- and C-terminal domains of ZBRK1 are important for inhibiting cell proliferation and anchorage-independent growth in cervical cancer. Specifically, the N-terminal KRAB domain of ZBRK1 displayed a more crucial role in inhibiting metastasis and invasion through modulation of KAP1 function in a transcriptionally dependent manner. The loss of ZBRK1 results in an increase of KAP1 expression, which enhanced migration and invasion of cervical cancer cells both the in vitro and in vivo. Moreover, an inverse correlation of expression levels was observed between ZBRK1 and KAP1 following tumor progression from in situ carcinoma to invasive/metastatic cervical cancer specimens. Taken together, the current results indicate that a loss of ZBRK1 contributes to the increased expression of KAP1, potentiating its role to enhance metastasis and invasion.


Assuntos
Invasividade Neoplásica , Metástase Neoplásica , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Neoplasias do Colo do Útero/patologia , Proteína BRCA1/metabolismo , Proliferação de Células , Feminino , Células HeLa , Humanos , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Repressoras/fisiologia , Proteína 28 com Motivo Tripartido , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(4): 510-5, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23841274

RESUMO

OBJECTIVE: To observe the effects of ginseng and Ligustrazine drug containing serum on the proliferation, vitality, and extracellular-signal-responsive kinase (ERK) pathway in neural stem cells undergoing in vitro oxygen-glucose deprivation/reoxygenation culture. METHODS: The cultured neural stem cells were randomly divided into 5 groups, i.e., the normal control group (Group A), the oxygen-glucose deprivation/reoxygenation group (Group B), the oxygen-glucose deprivation/reoxygenation +ginseng serum group (Group C), the oxygen-glucose deprivation/reoxygenation + Ligustrazine serum group (Group D), and oxygen-glucose deprivation/reoxygenation +ginseng and Ligustrazine drug serum group (Group E).The protein expression levels of ERK and phosphorylated ERK (p-ERK) were observed using immunoblotting. The proliferation of neural stem cells was observed using 5-bromodeoxyuridine (BrdU) incorporation assay. The vitality of neural stem cells was detected using methyl thiazolyl tetrazolium (MTT) colorimetry. RESULTS: The p-ERK level increased transiently at 10 min and 30 min after reoxygenation, but it decreased to the normal level at 4 h, 6 h, and 1 day, respectively. Compared with Group B, the p-ERK level at 6 h after reoxygenation could be elevated in Group C, D, and E. The proliferation and the vitality of neural stem cells at 1 day after reoxygenation could be enhanced. Furthermore, the effects of combination of ginseng and Ligusticum were better than those of using ginseng or Ligusticum alone. CONCLUSIONS: Combination of ginseng and Ligusticum could promote the proliferation and vitality of rats' neural stem cells undergoing oxygen-glucose deprivation/reoxygenation culture through ERK signal pathway. Its effects was better than that of using ginseng or Ligusticum alone.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Ligusticum/química , Masculino , Células-Tronco Neurais/citologia , Panax/química , Fosforilação , Pirazinas/farmacologia , Ratos , Ratos Sprague-Dawley
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