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1.
Biochem Biophys Res Commun ; 530(1): 189-195, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828284

RESUMO

Phosgene-induced lung injury is an important type of acute lung injury (ALI). Currently, no effective clinical treatment has been developed yet. Our previous study revealed that expressions of 6 miRNAs were significantly increased in phosgene-induced lung injury. The screened miRNA with the most significant effect on hepatocyte growth factor (HGF) expression by mesenchymal stem cells (MSCs) was transfected into MSCs. This study aimed to investigate whether the transfected MSCs had better therapeutic effects than MSCs alone. MSCs were co-cultured with miRNA mimics for 24h and 48h. HGF expression in culture supernatant was detected by ELISA. HGF expression in MSCs was detected by Western blot after being co-cultured with the selected miRNA inhibitor. The transfected MSCs were given to rats suffering from phosgene-induced lung injury. Expressions of TNF-α, IL-6, IL-1ß and IL-10, were assayed by ELISA. SP-C mRNA level was tested by RT-PCR. VE-CAD expression was tested by Western blot. We found that miRNA-378a-5p most increased HGF expression among the six miRNAs. After transfection of MSCs with miRNA-378a-5p inhibitor, HGF expression was decreased. Compared with untreated MSCs, MSCs transfected with miRNA-378a-5p exhibited more significant decreases in lung injury score, white blood cell count and protein content while restoring respiratory indexes. Meanwhile, expressions of TNF-α, IL-6, IL-1ß were decreased while those of IL-10, SP-C and VE-cadherin were increased. In conclusion, MSCs transfected with miRNA-378a-5p were more effective in treating phosgene-induced lung injury by repairing the secretion of alveolar epithelial cells and improving the permeability of vascular endothelial cells compared with MSCs alone.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Fosgênio/efeitos adversos , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/patologia , Animais , Células Cultivadas , Fator de Crescimento de Hepatócito/genética , Ratos , Ratos Sprague-Dawley , Transfecção , Regulação para Cima
2.
Biochem Biophys Res Commun ; 524(4): 876-882, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32057359

RESUMO

Sepsis is a progressive disease characterized by excessive inflammatory responses, severe tissue injury and organ dysfunction, ultimately leading to mortality. In this study, we demonstrated that thioredoxin-2 (TRX-2) expression is reduced in macrophages stimulated with lipopolysaccharide (LPS). Overexpression of TRX-2 significantly attenuated interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) production induced by LPS. TRX-2 inhibited LPS-induced inflammatory responses through suppressing activation of the NF-κB and MAPK signaling pathways. Furthermore, TRX-2 induced a significant decrease in mortality in mouse sepsis models in association with reduced inflammatory cytokine production and attenuation of organ injury. Our data collectively support a role of TRX-2 as a critical regulator of sepsis that influences survival by protecting the host from excessive inflammatory damage.


Assuntos
Macrófagos Peritoneais/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , NF-kappa B/genética , Choque Séptico/genética , Tiorredoxinas/genética , Animais , Regulação da Expressão Gênica , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Células RAW 264.7 , Choque Séptico/induzido quimicamente , Choque Séptico/mortalidade , Choque Séptico/patologia , Transdução de Sinais , Análise de Sobrevida , Tioglicolatos/farmacologia , Tiorredoxinas/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
3.
Nat Prod Res ; 34(17): 2448-2455, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30623680

RESUMO

A new polycyclic polyprenylated acylphloroglucinol (1), nujiangefolin D, together with five known analogues (2-6), were isolated from the fruits of Garcinia nujiangensis. Compound 1 was screened by the LC-MS and LC-PDA. The structure of 1 was elucidated on the basis of extensive spectroscopic techniques including 1 D and 2 D NMR and MS analyses. The compounds isolated were evaluated for their cytotoxic activities against three cancer cell lines, 1 showed moderate cytotoxic activity against Hela, PANC-1, and MDA-MB-231 cell lines with IC50 values of 5.6 ± 0.1, 9.1 ± 0.2, and 8.3 ± 0.2 µM, respectively. The antitumor mechanism was explained via virtual docking of 1 to the main sites in the human serine/threonine-protein kinase mTOR (mTOR) crystal structure (PDB code: 4DRI). Furthermore, 1 may inhibit Hela cell proliferation through mTOR by the western blotting analysis. Taken together, 1 may be a potential mTOR inhibitor used for the treatment of cervical cancer.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Garcinia/química , Floroglucinol/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Frutas/química , Humanos , Espectrometria de Massas , Simulação de Acoplamento Molecular , Estrutura Molecular , Floroglucinol/análogos & derivados , Floroglucinol/toxicidade , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias do Colo do Útero/tratamento farmacológico
4.
Biomed Pharmacother ; 115: 108871, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31026729

RESUMO

This study sought to clarify the role and underlying mechanisms of human serum albumin (HSA) therapy in global cerebral ischemia/reperfusion (GCI/R)-induced brain damage in rats. Five groups of adult male Wistar rats (n = 12 per group) were created as follows: sham operation (Sham), global cerebral ischemia/reperfusion (GCI/R), HSA treatment (GCI/R + HSA), Dickkopf-1 (DDK1) treatment (GCI/R + DDK1), and DDK1 plus HSA treatment (GCI/R + DKK1 + HSA). The GCI/R injury model was created using the modified Pusinelli four-vessel occlusion method. After 24 h, rats were evaluated using neurological scoring, Nissl staining, and brain tissue water content. The mRNA expression of Wnt, GSK3ß, and ß-Catenin in the brain were detected by quantitative real time polymerase chain reaction. The protein expression of ß-Catenin and GSK-3ß were investigated by western blot and immunohistochemical analysis in the presence and absence of the Wnt/ß-Catenin antagonist, DKK-1. Complex I activity and ROS content were also measured. After 24 h of reperfusion, the behavior score and brain tissue water content in the GCI/R + HSA group were lower than that in the GCI/R group. In addition, the degree of neuronal injury was significantly reduced in the GCI/R + HSA group (P < 0.05). The ROS content was significantly decreased and Complex I activity was markedly raised in the GCI/R + HSA group compared to the GCI/R group (P < 0.05). Further, GSK-3ß expression in the GCI/R + HSA group was lower than that in the GCI/R group, while the Wnt and ß-catenin expression were increased. These effects were reversed by DKK1. Taken together, we showed that HSA attenuates GCI/R-induced brain damage and may be neuroprotective via regulation of the Wnt/ß-catenin/ROS signaling pathway.


Assuntos
Isquemia Encefálica/patologia , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Albumina Sérica/farmacologia , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Distribuição Aleatória , Ratos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima , Proteínas Wnt/genética , beta Catenina/genética
5.
Am J Emerg Med ; 36(1): 27-32, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28673695

RESUMO

OBJECTIVE: Acute upper gastrointestinal bleeding (UGIB) is a potentially life-threatening condition that requires rapid assessment in the emergency department (ED). We aimed to compare the performance of the AIMS65, Glasgow-Blatchford (Blatchford), preendoscopic Rockall (pre-Rockall), and preendoscopic Baylor bleeding (pre-Baylor) scores in predicting 30-day mortality in patients with acute UGIB in the ED setting. METHODS: Consecutive patients with acute UGIB who were admitted to the ED ward during 2012-2016 were retrospectively recruited. Data were retrieved from the admission list of the ED using international classification of disease codes via computer registration. The predictive accuracy of these four scores was compared using the area under the receiver operating characteristic curve (AUC) method. RESULTS: Among the 395 patients included during the study period, the total 30-day mortality rate was 10.4% (41/395). The AIMS65 and Glasgow-Blatchford scores performed better with an AUC of 0.907 (95% confidence interval (CI), 0.852-0.963; P<0.001) and 0.870 (95% confidence interval, 0.833-0.902; P<0.001) compared with other scoring systems (preendoscopic Rockall score: AUC, 0.709; 95% CI, 0.635-0.784; P<0.001; preendoscopic Baylor score: AUC, 0.523; 95% CI, 0.472-0.573; P>0.05). CONCLUSION: In patients with acute UGIB in the ED, the AIMS65 and Glasgow-Blatchford scores are clinically more useful for predicting 30-day mortality than the preendoscopic Rockall and preendoscopic Baylor scores. The AIMS65 score might be more ideal for risk stratification in the ED setting.


Assuntos
Serviço Hospitalar de Emergência , Hemorragia Gastrointestinal/mortalidade , Índice de Gravidade de Doença , Doença Aguda , Idoso , Área Sob a Curva , China , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Recidiva , Estudos Retrospectivos , Medição de Risco/métodos , Centros de Atenção Terciária , Fatores de Tempo
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