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1.
Int J Mol Sci ; 19(7)2018 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-29933620

RESUMO

Unfolded protein response (UPR) is a cytoprotective mechanism that alleviates the protein-folding burden in eukaryotic organisms. Moderate activation of UPR is required for maintaining endoplasmic reticulum (ER) homeostasis and profoundly contributes to tumorigenesis. Defects in UPR signaling are implicated in the attenuation of various malignant phenotypes including cell proliferation, migration, and invasion, as well as angiogenesis. This suggests UPR as a promising target in cancer therapy. The pharmacological effects of the plant Scindapsus cf. hederaceus on human cancer cell lines is not understood. In this study, we identified an ethyl acetate extract from Scindapsus cf. hederaceus (SH-EAE), which markedly altered the protein expression of UPR-related genes in human non-small cell lung cancer (NSCLC) cells. Treatment with the SH-EAE led to the dose-dependent suppression of colony forming ability of both H1299 and H460 cells, but not markedly in normal bronchial epithelial BEAS-2B cells. SH-EAE treatment also attenuated the migration and invasion ability of H1299 and H460 cells. Moreover, SH-EAE strikingly suppressed the protein expression of two ER stress sensors, including inositol requiring enzyme-1α (IRE-1α) and protein kinase R-like ER kinase (PERK), and antagonized the induction of C/EBP homologous protein (CHOP) expression by thapsigargin, an ER stress inducer. SH-EAE induced the formation of massive vacuoles which are probably derived from ER. Importantly, SH-EAE impaired the formation of intersegmental vessels (ISV) in zebrafish larvae, an index of angiogenesis, but had no apparent effect on the rate of larval development. Together, our findings demonstrate, for the first time, that the ability of SH-EAE specifically targets the two sensors of UPR, with significant anti-proliferation and anti-migration activities as a crude extract in human NSCLC cells. Our finding also indicates potential applications of SH-EAE in preventing UPR activation in response to Tg-induced ER stress. We suggest that SH-EAE attenuates UPR adaptive pathways for rendering the NSCLC cells intolerant to ER stress.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Araceae/química , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Neovascularização Fisiológica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acetatos/química , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endorribonucleases/antagonistas & inibidores , Endorribonucleases/genética , Endorribonucleases/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Larva/efeitos dos fármacos , Neovascularização Fisiológica/genética , Extratos Vegetais/isolamento & purificação , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Solventes/química , Fator de Transcrição CHOP/antagonistas & inibidores , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Ensaio Tumoral de Célula-Tronco , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Peixe-Zebra , eIF-2 Quinase/antagonistas & inibidores , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
2.
Sci Rep ; 6: 35477, 2016 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-27752101

RESUMO

Magnetoplasmonic nanoparticles, composed of a plasmonic layer and a magnetic core, have been widely shown as promising contrast agents for magnetic resonance imaging (MRI) applications. However, their application in low-field nuclear magnetic resonance (LFNMR) research remains scarce. Here we synthesised γ-Fe2O3/Au core/shell (γ-Fe2O3@Au) nanoparticles and subsequently used them in a homemade, high-Tc, superconducting quantum interference device (SQUID) LFNMR system. Remarkably, we found that both the proton spin-lattice relaxation time (T1) and proton spin-spin relaxation time (T2) were influenced by the presence of γ-Fe2O3@Au nanoparticles. Unlike the spin-spin relaxation rate (1/T2), the spin-lattice relaxation rate (1/T1) was found to be further enhanced upon exposing the γ-Fe2O3@Au nanoparticles to 532 nm light during NMR measurements. We showed that the photothermal effect of the plasmonic gold layer after absorbing light energy was responsible for the observed change in T1. This result reveals a promising method to actively control the contrast of T1 and T2 in low-field (LF) MRI applications.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-252578

RESUMO

<p><b>OBJECTIVE</b>To observe the clinical effects of Biqi Capsule (BQC) combined with methotrexate (MTX) for treatment of rheumatoid arthritis (RA), and to study an effective protocol of RA treated by integrative medicine.</p><p><b>METHODS</b>One hundred and thirty-eight patients with RA were randomly assigned to Group I (44 cases, treated by BQC), Group II (46 cases, treated by MTX), and Group III (48 cases, treated by BQC combined with MTX). The therapeutic course for each group was 12 weeks. The degree of joint pain, the tender joint number, the tender joint index, the swollen joint number, the swollen joint index, the two-hand grip, the morning stiffness time, and related laboratory indices were observed in each group before and after treatment. The adverse reactions were recorded.</p><p><b>RESULTS</b>Compared with before treatment, there was statistical difference in the degree of joint pain, the tender joint number, the tender joint index, the swollen joint number, the swollen joint index, the two-hand grip, the morning stiffness time, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) in the 3 groups (P < 0.05, P < 0.01). Besides, better results were obtained in Group III (P < 0.01). As for the inter-group therapeutic efficacy, better results were obtained in Group III (P < 0.01). The gastrointestinal discomfort was the only adverse reaction in the 3 groups. No treatment was given due to its milder symptoms without any effects on the treatment.</p><p><b>CONCLUSIONS</b>BQC showed favorable effects on treating RA with no obvious adverse reaction. BQC combined with MTX showed better clinical efficacy than use of BQC or MTX alone. It could reduce the adverse reactions of MTX. BQC combined with MTX could reduce the toxic reactions and enhance the therapeutic effects, indicating it was an effective treatment program for RA.</p>


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antirreumáticos , Usos Terapêuticos , Artrite Reumatoide , Tratamento Farmacológico , Quimioterapia Combinada , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Metotrexato , Usos Terapêuticos , Fitoterapia , Resultado do Tratamento
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-299039

RESUMO

<p><b>OBJECTIVE</b>To observe the clinical efficacy of Wangbi Tablet (WT) on the treatment of knee osteoarthritis (KOA), and to study its treatment program by integrative medicine.</p><p><b>METHODS</b>The randomized, parallel control, and multi-center clinical observation method was used. 160 KOA patients of Gan-Shen deficiency complicated with stasis-blood blockade syndrome were assigned to three groups. Group A (72 cases) was treated by WT, Group B (42 cases) was treated by Votalin Tablet, and Group C (46 cases) was treated by WT + Votalin Tablet. All patients were treated for two months. Before and after treatment the clinical symptoms, the knee function activity, adverse reactions were observed and recorded. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) of each patient were respectively detected, statistically analyzed and compared.</p><p><b>RESULTS</b>After eight weeks of treatment significant difference was shown in the time of morning stiffness in joints, joint tendemess, swelling, pain, joint functional activities, ESR, and CRP between Group A and Group B (P<0.01). Besides, better effects were obtained in Group C (P<0.01). Improvement of ESR and CRP: They were obviously improved in the three groups after treatment (P<0.01). As for the markedly effective rate, better effects were obtained in Group C (P<0.05).</p><p><b>CONCLUSIONS</b>In the treatment of KOA, WT showed favorable effects with no obvious adverse reaction. The combination of WT and Voltaren Tablet was significantly superior to use of WT or Votalin Tablet alone. It could reduce the dosage of Voltaren Tablet and avoid adverse reactions of the gastrointestinal tract.</p>


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Medicina Integrativa , Osteoartrite do Joelho , Tratamento Farmacológico , Fitoterapia , Comprimidos
5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-332581

RESUMO

<p><b>OBJECTIVE</b>To observe the therapeutic effect of total glucosides of paeony (TGP) on lupus nephritis (LN) in MRL/lpr mice.</p><p><b>METHODS</b>MRL/lpr mice with lupus nephritis were randomized into model group and TGP group. The urinary protein content was detected using Coomassie brilliant blue, and the serum levels of IgG anti-double-stranded DNA (dsDNA) antibodies and antinuclear antibodies (ANA) were measured by enzyme-linked immunosorbent assay (ELISA). The changes in the renal pathology were examined microscopically, and the spleen and thymus were weighed to calculate the spleen and thymus indexes.</p><p><b>RESULTS</b>At 15 and 30 days after TGP administration, the urinary protein content in the TGP group was significantly lower than that in the model group (P<0.05). TGP treatment significantly lowered the serum levels of anti-dsDNA antibodies and ANA and the weight and index of spleen (P<0.05), resulting also in lessened renal pathology at 30 days after the administration. Compared to those before TGP treatment, the urinary protein content and the levels of anti-dsDNA antibodies and ANA decreased significantly at 15 and 30 days after TGP administration (P<0.05), while in the model group, the level of anti-dsDNA increased significantly without obvious changes in urinary protein content or ANA. At 30 days after TGP administration, the urinary protein content was significantly lowered in the TGP group as compared to that at 15 days (P<0.05), but the antibodies showed no significant changes.</p><p><b>CONCLUSION</b>TGP can reduce urinary protein content and serum levels of anti-dsDNA antibodies and ANA, and lessen renal pathology in MRL/lpr mice with lupus nephritis, suggesting its therapeutic effect on lupus nephritis.</p>


Assuntos
Animais , Feminino , Masculino , Camundongos , Anticorpos Antinucleares , Sangue , Autoanticorpos , Sangue , DNA , Alergia e Imunologia , Glucosídeos , Farmacologia , Nefrite Lúpica , Sangue , Tratamento Farmacológico , Urina , Camundongos Endogâmicos MRL lpr , Paeonia , Química , Proteinúria , Tratamento Farmacológico
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