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1.
Biomed Pharmacother ; 161: 114462, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36933380

RESUMO

Glioblastoma (GBM) is a human malignant tumor with low survival and high recurrence rate. Angelicin, an active furanocoumarin compound, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of angelicin on GBM cells and its mechanism are still unclear. In this study, we found that angelicin inhibited the proliferation of GBM by inducing the cell cycle arrested in G1 phase and suppressed the migration of GBM cells in vitro. Mechanically, we found that angelicin downregulated the expression of YAP and decreased the nuclear localization of YAP, and suppressed the expression of ß-catenin. Furthermore, overexpression of YAP partially restored the inhibitory effect of angelicin on GBM cells in vitro. Finally, we found that angelicin could inhibit the growth of tumor and reduce the expression of YAP in the subcutaneous xenograft model of GBM in nude mice and the syngeneic intracranial orthotopic model of GBM in C57BL/6 mice. Taken together, our results suggest that the natural product angelicin exerts its anticancer effects on GBM via YAP signaling pathway, and is expected to be a promising compound for the treatment of GBM.


Assuntos
Neoplasias Encefálicas , Furocumarinas , Glioblastoma , Animais , Camundongos , Humanos , Glioblastoma/patologia , Camundongos Nus , Proliferação de Células , Camundongos Endogâmicos C57BL , Transdução de Sinais , Furocumarinas/farmacologia , Furocumarinas/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Encefálicas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Biomed Pharmacother ; 158: 114203, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36916429

RESUMO

BACKGROUND: Neferine exhibits therapeutic effects on anti-hypertension. However, the effect of neferine on hypertensive vascular remodeling remains unexplored. Therefore, the current study was to investigate the effect of neferine on hypertensive vascular remodeling and its underlying mechanisms. METHODS: Total 30 male spontaneously hypertensive rats (SHRs) were divided randomly into five groups, including SHR, Neferine-L (2.5 mg/kg/day), Neferine-M (5 mg/kg/day), Neferine-H (10 mg/kg/day), and Valsartan (10 mg/kg/day) groups (n = 6 for each group). Wistar Kyoto (WKY) rats were set as control group (n = 6). Noninvasive blood pressure system, ultrasound, hematoxylin and eosin staining, masson trichrome staining were used to detect the blood pressure, pulse wave velocity (PWV), pathological changes and collagen content in abdominal aortas of SHRs. RNA-sequencing and immunohistochemistry(IHC) analyses were used to identify and verify the differentially expressed transcripts and activation of associated signaling pathways in SHRs. RESULTS: Various concentrations of neferine or valsartan treatment substantially reduced the elevation of blood pressure, PWV, and abdominal aortic thickening of SHRs. RNA-sequencing and KEGG analyses recognized 441 differentially expressed transcripts and several enriched pathways (including PI3K/AKT and TGF-ß/Smad2/3 signaling pathways) after neferine treatment. Masson trichromatic staining and IHC analysis demonstrated that neferine treatment decreased the collagen content and down-regulated the protein expression of PCNA, collagen I & III, and fibronectin, as well as p-PI3K, p-AKT, TGF-ß1 and p-Smad2/3 in abdominal aortic tissues of SHRs. CONCLUSION: Neferine treatment exhibits therapeutic effects on anti-hypertension and reduces vascular remodeling, as well as suppresses the abnormal activation of multiple signaling pathways, including PI3K/AKT and TGF-ß1/Smad2/3 pathways.


Assuntos
Hipertensão , Fator de Crescimento Transformador beta1 , Ratos , Animais , Masculino , Ratos Endogâmicos SHR , Fator de Crescimento Transformador beta1/metabolismo , Ratos Endogâmicos WKY , Remodelação Vascular , Análise de Onda de Pulso , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Hipertensão/metabolismo , Pressão Sanguínea , Transdução de Sinais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Valsartana/farmacologia , Valsartana/uso terapêutico , Colágeno/metabolismo , RNA
3.
Zhen Ci Yan Jiu ; 47(12): 1080-7, 2022 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-36571223

RESUMO

OBJECTIVE: To observe the effect of acupotomy on the expression of Beclin-1, Bcl-2 and Caspase-3 in the cartilage tissue in rabbits with knee osteoarthritis (KOA), so as to explore its mechanism underling improvement of KOA. METHODS: Twenty-four healthy male New Zealand rabbits were randomly and equally divided into blank control, model and acupotomy groups, with 8 rabbits in each group. By using the modified Videman's methods, the KOA model was established by left hind limb immobilization with a plaster cast for 6 weeks. The severity of KOA (knee pain, swelling and motor function) was assessed using Lequesne score, and the rabbits with a score below 4 were excluded. The acupotomy was applied to "Hedingci" (the attachment of the quadriceps tendon to the patella at the upper edge), "Binneixia" (the medial patellar supporting band attachment of medial inferior patellar margin), "Binwaixia" (the lateral patellar supporting band attachment of the lower lateral patellar margin), "Chengfeijian" (the lateral collateral ligament of the knee passes over the lateral joint space), "Weiyangci" (the medial margin of biceps femoris at the lateral end of popliteus), "Yinlingci" (the medial tibial attachment of anserinus tendon) on the left hind limb once a week for 4 weeks. One week after the last intervention, the left knee joint dysfunction severity(pain, maximum walking distance, and some activities of daily living) was evaluated by using modified Lequesne score. Histopathological changes of the cartilage were observed under light microscope after H.E. staining. The apoptosis of chondrocytes was observed after terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labeling (TUNEL) staining. The autophagolysosomes of chondrocytes were observed using transmission electron microscopy. The expression levels of Beclin-1, Bcl-2 and Caspase-3 (related factors of autophagy and apoptosis) were detected using Real-time PCR and Western blot separately. RESULTS: In comparison with the blank control group, the Lequesne score, apoptosis rate, expression levels of Caspase-3 mRNA and protein were significantly increased (P<0.001), and the number of autophagolysosomes, expression levels of Beclin-1 and Bcl-2 mRNAs and proteins considerably decreased (P<0.001) in the model group. Relevant to the model group, the acupotomy group had an obvious decrease in Lequesne score, rate of apoptosis, and expression levels of Caspase-3 mRNA and protein (P<0.001) and an apparent increase in the number of autophagolysosomes and expression levels of Beclin-1 and Bcl-2 mRNAs and proteins (P<0.001). Findings of H.E. staining showed severe damaged cartilage surface, with a large number of exfoliation defects, few chondrocytes on the surface and disordered arrangement of transitional cells in the model group, which was relatively milder in the acupotomy group. CONCLUSION: Acupotomy can mitigate knee-joint pain and improve functional activity in KOA rabbits, which may be associated with its functions in promoting autophagy and suppressing apoptosis by up-regulating expressions of Beclin-1 and Bcl-2 mRNAs and proteins and down-regulation of Caspase-3 mRNA and protein.


Assuntos
Terapia por Acupuntura , Osteoartrite do Joelho , Animais , Masculino , Coelhos , Atividades Cotidianas , Apoptose , Proteína Beclina-1/genética , Cartilagem/metabolismo , Caspase 3/genética , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/terapia , Dor , Proteínas Proto-Oncogênicas c-bcl-2 , RNA Mensageiro
4.
PLoS One ; 17(12): e0279851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584147

RESUMO

We assessed the role of the protein-coding gene chaperonin-containing TCP1 subunit 6A (CCT6A) in osteosarcoma, as this is currently unknown. Using data from the R2 online genomic analysis and visualization application, we found that CCT6A messenger ribonucleic acid (RNA) expression is increased in osteosarcoma tissue and cells. Transfection of CCT6A small interfering RNA into cultured osteosarcoma cells revealed that CCT6A knockdown attenuates cell growth, cell viability, cell survival, and induced apoptosis and cell cycle progression at the G0/G1 phases. Moreover, CCT6A knockdown downregulated phospho-protein kinase B (p-Akt), cyclinD1 and B-cell lymphoma-2, whereas upregulated Bcl-2-associated X-protein expression. Thus, CCT6A knockdown inhibits cell proliferation, induces cell apoptosis, and suppresses the Akt pathway.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células/genética , Ciclo Celular , Fase G1 , Osteossarcoma/genética , Osteossarcoma/metabolismo , Linhagem Celular Tumoral , Apoptose/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Chaperonina com TCP-1/genética , Chaperonina com TCP-1/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-36437834

RESUMO

Acupotomy intervention (AI) is an available treatment for knee osteoarthritis (KOA) in China, which is a common health problem over the world. However, the underlying mechanism of AI on the KOA treatment is still unknown. To further understand the mechanism of acupotomy in treating KOA, the morphological observation and TMT proteomic analyses were conducted in rabbits. By using X-ray and MRI, we found that the space of the knee joint was bigger in AI than in KOA. Moreover, the chondrocytes were neatly arranged in AI but disordered in KOA. With proteomic analyses in chondrocytes, 68 differently accumulated proteins (DAPs) were identified in AI vs. KOA and DAPs related to energy metabolism and the TCA cycle were suggested to play a central role in response to AI. Furthermore, AIFM1 was proposed to be an important regulator in controlling the energy production in mitochondrial. Besides, FN1, VIM, COL12A1, COL14A1, MYBPH, and DPYSL3 were suggested to play crucial roles in AI for the treatment of KOA. Our study was systematically elucidating the regulation mechanism of acupotomy intervention in the treatment of KOA.

6.
Huan Jing Ke Xue ; 36(6): 2306-13, 2015 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-26387340

RESUMO

Due to the collapse of the Pb/Zn tailing dam of Huanjiang, Guangxi, the farmland along Huanjiang River are strongly acidic and heavy metal-contaminated, resulting in the loss of agricultural production. To explore some remedies and the migration of heavy metals in heavy metal contaminated-soil of Huanjiang, this study investigated the effects of different types of amendments (lime, calcium magnesium phosphate, organic fertilizer, polypropylene amide) on tested soils through soil leaching test. The results showed that T1 soil was severely acidified, reducing the pH of the soil layer to clean contact, while T2, T3, T4, T5 could significantly improve the contaminated soil pH, ranging from 2.7 to 3.2, 1.6 to 2.7 respectively. Compared with T1, in the contaminated soil at 0-20 cm, T2, T3, T4, T5 could effectively activate Pb and immobilize Zn. Compared with T1, in 20-60 cm clean soil, there was no significant differences in the effect of different treatments on DTPA-Pb and DTPA-Zn (P < 0.05). Compared with T1, T4 and T5 could provide good growing conditions for plants, which might provide technical support for future measurements such as bioremediation.


Assuntos
Chumbo/química , Poluentes do Solo/isolamento & purificação , Solo/química , Zinco/química , Agricultura , Amidas , Compostos de Cálcio , China , Recuperação e Remediação Ambiental , Fertilizantes , Imobilização , Óxidos , Fosfatos , Polipropilenos , Rios
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