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1.
J Pharm Pharmacol ; 76(6): 656-671, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38429940

RESUMO

BACKGROUND: We administered Bushen Huoxue Huazhuo Formula (BSHXHZF) and transplanted bone marrow mesenchymal stem cells (BMSCs) into mice with Wilson's disease (WD)-related liver fibrosis to evaluate the liver-protecting mechanism of this prescription. METHODS: Mice, randomly divided into different treatment groups, showed histopathological changes and degree of hepatocyte apoptosis. For hepatic hydroxyproline (Hyp) determination, transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-7 (BMP-7) mRNA and protein were measured. Chemical profiling of the extract of BSHXHZF using The liquid chromatography-mass spectrometry (LC-MS/MS) and revealing its antifibrosis mechanism using metabolomics. RESULTS: TCM+BMSC group livers exhibited few inflammatory cells. TUNEL revealed abundant brown apoptotic cells in model control groups, while the TCM+BMSC groups showed a significant increase in blue negative expression of liver cells. Hyp in toxic milk (TX) mice groups was significantly lower than that in model control groups (MG). Compared with MG, TGF-ß1 expression was significantly lower than all other groups, while BMP-7 expression was significantly higher. Metabolic analysis identified 20 potential biomarkers and 10 key pathways, indicating that BSHXHZF+BMSC intervention has a significant regulatory effect on metabolic disorders of these small molecule substances. CONCLUSION: BSHXHZF combined with BMSCs can inhibit liver fibrosis and hepatocyte apoptosis by improving related metabolic disorders, and achieving therapeutic effects in WD-related liver fibrosis.


Assuntos
Proteína Morfogenética Óssea 7 , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Degeneração Hepatolenticular , Cirrose Hepática , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Metabolômica , Fator de Crescimento Transformador beta1 , Animais , Cirrose Hepática/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Metabolômica/métodos , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Degeneração Hepatolenticular/terapia , Degeneração Hepatolenticular/metabolismo , Degeneração Hepatolenticular/tratamento farmacológico , Proteína Morfogenética Óssea 7/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Apoptose/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Espectroscopia de Prótons por Ressonância Magnética , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Hidroxiprolina/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-33564316

RESUMO

RESULTS: Firstly, 324 active compounds have been identified in the GDL formula. Meanwhile, we identified 1496 human genes which are related to WD or liver cirrhosis. Functional and pathway enrichment analysis indicated that NOD-like receptor signaling pathway, bile secretion, calcium signaling pathway, steroid hormone biosynthesis, T cell receptor signaling pathway, apoptosis, MAPK signaling pathway, and so forth can be obviously regulated by GDL. Further, in a mouse model of WD, in vivo experiments showed that GDL treatment can not only reduce the pathological symptoms of the liver but also reduce the apoptosis of hepatocytes. CONCLUSIONS: In this study, systemic pharmacological methods were proposed and the mechanism of GDL combined therapy for WD was explored. This method can be used as a reference for the study of other mechanisms of traditional Chinese medicine.

3.
Sci Rep ; 11(1): 1377, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446761

RESUMO

Wilson's Disease (WD), an ATP7B-mutated inherited disease that affects copper transport, is characterised by liver and nervous system manifestations. Long non-coding (ln-c) RNAs are widely involved in almost all physiological and pathological processes in the body, and are associated with numerous diseases. The present study aimed to elucidate the lncRNA-mRNA regulation network in a TX WD mouse model using RNA sequencing (RNA-seq). lncRNA expression profiles were screened using RNA-seq and real-time polymerase chain reaction, and differentially expressed lncRNAs and mRNAs were identified. To analyse the biological functions and pathways for the differentially expressed mRNAs, gene ontology and pathway enrichment analyses were performed. A significantly correlated lncRNA-mRNA relationship pair was calculated by CNC analysis to construct differential lncRNA and mRNA co-expression networks. A total of 2564 significantly up-regulated and 1052 down-regulated lncRNAs, and 1576 up-regulated and 297 down-regulated mRNAs, were identified. These genes were found to be associated with key processes such as apoptosis, and KEGG analysis revealed enrichment in the drug metabolism-cytochrome P450 pathway, PPAR signalling pathway, Notch signalling pathway, and MAPK signalling pathway. The identified differential lncRNAs may be involved in the pathogenesis and development of WD liver injury.


Assuntos
Regulação da Expressão Gênica , Degeneração Hepatolenticular/metabolismo , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases , RNA Longo não Codificante/biossíntese , Animais , Degeneração Hepatolenticular/genética , Camundongos , RNA Longo não Codificante/genética
4.
J Int Med Res ; 48(6): 300060520930156, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32567965

RESUMO

OBJECTIVES: Caregiver burden in neurologic Wilson disease (NWD) has received little attention. We investigated predictors of caregiver burden in Chinese NWD patients. METHODS: Participants in this retrospective study were NWD patients admitted to The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from 1 August to 31 December 2019. Sociodemographic information was recorded for caregivers and NWD patients. Caregiver burden was evaluated using the Caregiver Burden Inventory (CBI). Cognitive impairment, functional problems, depression and anxiety were evaluated by professional interviewers. Path analysis was used to evaluate predictors of CBI scores. RESULTS: Sixty NWD patients were enrolled (mean age: 21.35 ± 4.89 years; mean NWD duration: 7.85 ± 3.11 years). The mean CBI score was 52.00 ± 17.16. Care duration had a significant direct effect on CBI score after controlling for confounders (r = 0.493). Cognitive impairment (r = -0.426), functional problems (r = 0.581), depression (r = 0.349) and anxiety (r = 0.317) had significant indirect effects on CBI score. CONCLUSION: Caregivers of NWD patients may experience a medium level of caregiver burden. NWD duration, cognitive impairment, functional problems, depression and anxiety in NWD patients may be useful predictors of caregiver burden.


Assuntos
Sobrecarga do Cuidador/psicologia , Cuidadores/psicologia , Degeneração Hepatolenticular/psicologia , Adolescente , Adulto , Idoso , Ansiedade/psicologia , Povo Asiático/psicologia , Sobrecarga do Cuidador/etiologia , China/epidemiologia , Efeitos Psicossociais da Doença , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Adulto Jovem
5.
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 , Catéteres , 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
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