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1.
Artigo em Inglês | MEDLINE | ID: mdl-37839537

RESUMO

Reserpine is a drug that is commonly used as an antihypertensive and antipsychotic drug in clinical practice. During our previous research, we found that reserpine treatment in zebrafish larvae can cause depression-like behaviors, but the corresponding mechanisms are still unclear. In this study, we aimed to investigate the molecular mechanism by which reserpine exposure affects locomotor behaviors in larval zebrafish through transcriptome analysis. The gene enrichment results showed that the differentially highly expressed genes of zebrafish are mainly enriched in voltage-gated ion channels, dopaminergic synapses and wnt signaling pathways. Selected genes (apc2, cacna1aa, drd2b, dvl1a, fzd1, wnt1, wnt3a, wnt9a and wnt10a) by transcriptomic results was validated by real-time PCR. Consistently, Wnt signaling pathway inhibitor XAV939 may induce reduced behavioral changes in zebrafish larvae, while the Wnt signaling pathway agonist SB415286 reversed the reserpine-induced depressive effects. Our study provides gene transcriptional profile data for future research on reserpine-induced locomotor behavioral changes.


Assuntos
Transcriptoma , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Reserpina/farmacologia , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Perfilação da Expressão Gênica
2.
Can J Gastroenterol Hepatol ; 2023: 6882851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37766807

RESUMO

Human antigen R (HuR), also known as ELAVL1, is a widely expressed RNA-binding protein (RBP) that has a significant impact on the development and advancement of tumors. Our previous study found that 5-fluorouracil (5-FU) may impede the proliferation and increase apoptosis in gastric cancer cells by reducing the nucleocytoplasmic shuttling of HuR. However, how posttranscriptional regulation influences HuR functions in gastric cancer remains to be elucidated. Here, we demonstrated that miR-325-3p has the potential to regulate the expression level of HuR by directly binding to its 3'UTR, which in turn led to a significant reduction in proliferation and an increase in apoptosis in gastric cancer cells. In addition, xenograft experiment showed that knockdown of HuR or overexpression of miR-325-3p group exhibited smaller tumor sizes after transplant of gastric cancer cells into zebrafish larvae. Thus, our findings offer new insights into the pathogenesis of gastric cancer and may potentially assist in identifying novel targets for drug therapy.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Animais , Neoplasias Gástricas/genética , Peixe-Zebra , Apoptose/genética , Fluoruracila/farmacologia , Proliferação de Células/genética , MicroRNAs/genética
3.
Immunobiology ; 228(4): 152412, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37343439

RESUMO

Sepsis is a life-threatening systemic organ dysfunction caused by the host's unregulated response to a widespread bacterial infection. Endothelial injury is a major pathophysiologic symptom of sepsis and is considered a critical factor in promoting the progression of disease severity. ELAV like RNA binding protein 1(ELAVL1) is a ubiquitously expressed RNA-binding protein that may play an important role during sepsis. Nonetheless, the molecular mechanisms of ELAVL1 on endothelial cell damage in sepsis have not been well defined. Here, we aimed to confirm the role of ELAVL1 in sepsis-induced endothelial cell damage using lipopolysaccharide (LPS)-induced zebrafish and endothelial cells (ECs) models. We found that zebrafish larvae treated with LPS exhibited systemic endothelial cell damage, mostly manifested as pericardial edema, curved tail, and impaired angiogenesis. LPS treatments also significantly induced the expression levels of inflammatory cytokines (interleukin-6 (IL-6), IL-8, and tumor necrosis factor (TNF)-α) in vivo. In vitro, we observed the increase of ELAVL1 cytoplasmic translocation with LPS treatment. Mechanistically, targeted disruption of the ELAVL1 gene decreased the expression of TNF-α, IL-6, and IL-8 during induction of sepsis and alleviated LPS-induced blood vessel injury in zebrafish. Taken together, our study indicates that ELAVL1 knockdown may alleviate sepsis-induced endothelial cells injury by suppressing cytokine storm. Our research suggests that inhibition of ELAVL1 could reduce the level of inflammatory cytokine production induced by LPS and protect against endothelial cell injury. ELAVL1 might be a potential therapeutic target to block endothelial cells injury associated with sepsis.


Assuntos
Interleucina-6 , Sepse , Animais , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Células Endoteliais/metabolismo , Peixe-Zebra/metabolismo , Síndrome da Liberação de Citocina/metabolismo , Interleucina-8/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Sepse/tratamento farmacológico
4.
Prostaglandins Other Lipid Mediat ; 158: 106609, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34954219

RESUMO

The arachidonic acid (AA) metabolism pathways play a key role in immunological response and inflammation diseases, such as asthma, etc. AA in cell membranes can be metabolized by lipoxygenases (LOXs) to a screen of bioactive substances that include leukotrienes (LTs), lipoxins (LXs), and eicosatetraenoic acids (ETEs), which are considered closely related to the pathophysiology of respiratory allergic disease. Studies also verified that drugs regulating AA LOXs pathway have better rehabilitative intervention for asthma. This review aims to summarize the physiological and pathophysiological importance of AA LOXs metabolism pathways in asthma and to discuss its prospects of therapeutic strategies.


Assuntos
Asma , Lipoxinas , Araquidonato 5-Lipoxigenase , Araquidonato Lipoxigenases , Asma/tratamento farmacológico , Humanos , Leucotrienos , Lipoxigenases
5.
Expert Rev Respir Med ; 14(9): 949-956, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32421402

RESUMO

Objectives: Lung abscess is an infectious lung disease. The main objective of this review was to assess the efficacy and safety of percutaneous tube drainage (PTD) in patients with lung abscess by systematic review and meta-analysis of published data. Methods: We searched all literature published between 1 January 2010, and 6 August 2019, in the PubMed, Cochrane Central Library, EMBASE, Wanfang, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature databases for relevant reports. The data from these studies were pooled for statistical analysis, and sensitivity analysis and risk-of-bias analysis was performed. Results: Meta-analysis revealed that percutaneous tube drainage (PTD) was superior to conservative treatment in terms of the total effectivity rate (P < 0.01). Moreover, length of hospital stay and number of fever days were reduced for the PTD group than for the group receiving conservative treatment (P < 0.01). There was no significant difference between PTD and conservative treatment in terms of complication rate (P = 0.43). Conclusion: Lung abscess drainage is a safe and effective method for treating lung abscesses. Based on the principle that as much drainage as possible should be performed as treatment of abscess diseases, drainage should be promoted as treatment for lung abscess.


Assuntos
Drenagem , Abscesso Pulmonar/terapia , Adulto , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Segurança do Paciente , Resultado do Tratamento
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