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1.
Chin J Nat Med ; 17(7): 535-544, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514985

RESUMO

The aim of this study is to investigate the protective effects of a small molecular fraction (SMF) of Polygoni multiflori Radix Praeparata (PMRP) in a cyclophosphamide (CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay (ELISA); The level of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase (GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects.

2.
J Exp Clin Cancer Res ; 38(1): 214, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118109

RESUMO

BACKGROUND: Gastric cancer is one of the deadliest malignant tumours, with a high incidence in China, and is regulated by aberrantly overexpressed oncogenes. However, existing therapies are insufficient to meet patients' needs; thus, the identification of additional therapeutic targets and exploration of the underlying mechanism are urgently needed. GPAA1 is the subunit of the GPI transamidase that transfers the GPI anchor to proteins within the ER. The functional impacts of increased expression levels of GPAA1 in human cancers are not well understood. METHODS: Data mining was performed to determine the pattern of GPAA1 expression and the reason for its overexpression in tumour and adjacent normal tissues. In vitro and in vivo experiments evaluating proliferation and metastasis were performed using cells with stable deletion or overexpression of GPAA1. A tissue microarray established by the Ren Ji Hospital was utilized to analyse the expression profile of GPAA1 and its correlation with prognosis. Western blotting, an in situ proximity ligation assay, and co-immunoprecipitation (co-IP) were performed to reveal the mechanism of GPAA1 in gastric cancer. RESULTS: GPAA1 was a markedly upregulated oncogene in gastric cancer due to chromosomal amplification. GPAA1 overexpression was confirmed in specimens from the Ren Ji cohort and was associated with ERBB2 expression, predicting unsatisfactory patient outcomes. Aberrantly upregulated GPAA1 dramatically contributed to cancer growth and metastasis in in vitro and in vivo studies. Mechanistically, GPAA1 enhanced the levels of metastasis-associated GPI-anchored proteins to increase tumour metastasis and intensified lipid raft formation, which consequently promoted the interaction between EGFR and ERBB2 as well as downstream pro-proliferative signalling. CONCLUSIONS: GPAA1 facilitates the expression of cancer-related GPI-anchored proteins and supplies a more robust platform-the lipid raft-to promote EGFR-ERBB2 dimerization, which further contributes to tumour growth and metastasis and to cancer progression. GPAA1 could be a promising diagnostic biomarker and therapeutic target for gastric cancer.

3.
Gut ; 2019 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-30826748

RESUMO

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. Neurotransmitter-initiated signalling pathway is profoundly implicated in tumour initiation and progression. Here, we investigated whether dysregulated neurotransmitter receptors play a role during pancreatic tumourigenesis. METHODS: The Cancer Genome Atlas and Gene Expression Omnibus datasets were used to identify differentially expressed neurotransmitter receptors. The expression pattern of gamma-aminobutyric acid type A receptor pi subunit (GABRP) in human and mouse PDAC tissues and cells was studied by immunohistochemistry and western blot analysis. The in vivo implications of GABRP in PDAC were tested by subcutaneous xenograft model and lung metastasis model. Bioinformatics analysis, transwell experiment and orthotopic xenograft model were used to identify the in vitro and in vivo effects of GABRP on macrophages in PDAC. ELISA, co-immunoprecipitation, proximity ligation assay, electrophysiology, promoter luciferase activity and quantitative real-time PCR analyses were used to identify molecular mechanism. RESULTS: GABRP expression was remarkably increased in PDAC tissues and associated with poor prognosis, contributed to tumour growth and metastasis. GABRP was correlated with macrophage infiltration in PDAC and pharmacological deletion of macrophages largely abrogated the oncogenic functions of GABRP in PDAC. Mechanistically, GABRP interacted with KCNN4 to induce Ca2+ entry, which leads to activation of nuclear factor κB signalling and ultimately facilitates macrophage infiltration by inducing CXCL5 and CCL20 expression. CONCLUSIONS: Overexpressed GABRP exhibits an immunomodulatory role in PDAC in a neurotransmitter-independent manner. Targeting GABRP or its interaction partner KCNN4 may be an effective therapeutic strategy for PDAC.

4.
J Nat Med ; 73(2): 388-396, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30617707

RESUMO

To investigate if andrographolide impairs cholestatic liver injury. All rats were randomly divided into six groups-(1) control (n = 6), (2) control + 200 mg/kg andrographolide (n = 6), (3) alpha-naphthylisothiocyanate (ANIT)-control (n = 6), (4) ANIT + 50 mg/kg andrographolide (n = 6), (5) ANIT + 100 mg/kg andrographolide (n = 6), and (6) ANIT + 200 mg/kg andrographolide (n = 6). We gavaged 50 mg/kg ANIT to mimic cholestatic liver injury in rats. Seven days after treatment, all the rats were killed. Serum biochemistry and hepatic histopathological assays were performed to evaluate liver injury. We observed that 200 mg/kg andrographolide significantly decreased the level of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, total bilirubin, and total bile acid in the blood. It also markedly decreased hepatic interleukin-6 and tumor necrosis factor α. Furthermore, 200 mg/kg andrographolide significantly decreased malondialdehyde but increased superoxide dismutase, glutathione, and erythrocyte glutathione peroxidase. Moreover, 200 mg/kg andrographolide effectively increased the accumulation of sirtuin 1 and nuclear erythroid 2-related factor-2. It also attenuated the level of nuclear factor kappa-light-chain-enhancer of activated B and cyclooxygenase-2. These data suggest that andrographolide may impair cholestatic liver injury via anti-inflammatory and anti-oxidative stress.


Assuntos
Colestase/tratamento farmacológico , Diterpenos/uso terapêutico , Fígado/efeitos dos fármacos , 1-Naftilisotiocianato , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Colestase/sangue , Colestase/induzido quimicamente , Diterpenos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas , Inflamação/prevenção & controle , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sirtuína 1/metabolismo
5.
Clin Cancer Res ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30420446

RESUMO

PURPOSE: Extensive research has reported that the tumor microenvironment components play crucial roles in tumor progression. Thus, blocking the supports of tumor microenvironment is a promising approach to prevent cancer progression. We aimed to determine whether blocking extracellular ATP-P2RY2 axis could be a potential therapeutic approach for PDAC treatment. EXPERIMENTAL DESIGN: Expression of P2RY2 was determined in 264 human PDAC samples, and correlated to patient survival. P2RY2 was inhibited in human PDAC cell lines by antagonist and shRNA, respectively, and cell viability, clonogenicity and glycolysis were determined. RNA sequencing of PDAC cell line was applied to reveal underlying molecular mechanisms. Multiple PDAC mouse models were used to assess the effects of the P2RY2 inhibition on PDAC progression. RESULTS: P2RY2 was upregulated and associated with poor prognosis in PDAC. Activated P2RY2 by increased extracellular ATP in tumor microenvironment promoted PDAC growth and glycolysis. Further studies showed that the agonist-activated P2RY2 triggered PI3K/AKT-mTOR signaling by crosstalk with PDGFR mediated by Yes1, resulting in elevating expression of c-Myc and HIF1a, which subsequently enhanced cancer cell glycolysis. Genetic and pharmacological inhibition of P2RY2 impaired tumor cell growth in subcutaneous and orthotopic xenograft model, as well as delayed tumor progression in inflammation-driven PDAC model. Additionally, synergy was observed when AR-C118925XX, the selective antagonist of P2RY2 receptor, and gemcitabine were combined, resulting in prolonged survival of xenografted PDAC mice. CONCLUSIONS: These findings revealed the roles of the P2RY2 in PDAC metabolic reprogramming, suggesting that P2RY2 might be a potential metabolic therapeutic target for PDAC.

6.
Huan Jing Ke Xue ; 39(10): 4422-4429, 2018 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-30229587

RESUMO

Primary pollutants of air quality in Beijing, Baoding, Shijiazhuang, Xingtai, and Handan cities along the Taihang Mountains were analyzed to investigate their spatial distribution characteristics and temporal variation trends during 2014-2016. The results showed that the primary pollutants were ranked as PM2.5, O3-8h, NO2 and PM10 from most to least important in Beijing, and PM2.5, PM10, O3-8h, NO2, SO2 and CO in the other four cities. Three-year average percentages of days with PM2.5 as the primary pollutant in each city were similar (53.3%-58.1%), however, percentages of days with PM10 as primary pollutant increased, while percentages of O3-8h decreased basically, from north to south. Except for Handan with a significant descending trend, percentages of days with PM2.5 as primary pollutant varied slightly in the other four cities during the study period, and percentages of O3-8h of Shijiazhuang, Xingtai and Handan increased significantly in 2016. Percentages of NO2 slightly declined year by year in Beijing, and the other four cities mainly showed the opposite trend. Monthly variation curves of days with PM2.5 and O3-8h as primary pollutants showed "W" and "inverted U" types respectively, while the high value interval of days with PM10 as primary pollutant occurred between March and May. With the exception of Beijing, peak of monthly variation curves for days with NO2 as the primary pollutant was occurred in October in the other four cities. From "moderate" to "hazardous" levels for air quality, the percentages of days with PM2.5 and/or PM10 as primary pollutants increased level by level, with percentages of PM10 trending downwards and PM2.5 upwards. Meanwhile, days with O3-8h as the primary pollutant mostly appeared in the range between "moderate" and "unhealthy" levels, and NO2 was only prominent in "moderate" level.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(7): 554-558, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30022757

RESUMO

OBJECTIVE: To study the relationship between the expression of peripheral blood HLA-DR, CD4+CD25+ regulatory T cells, IL-17 and IL-27 with liver damage in children with human cytomegalovirus (HCMV) infection. METHODS: Twenty-one HCMV children with liver damage and twenty-one HCMV children without liver damage were enrolled in this study. The expression of peripheral blood HLA-DR and CD4+CD25+ regulatory T cells was detected by flow cytometry. Plasma levels of IL-17 and IL-27 were measured using ELISA. RESULTS: The plasma levels of IL-17 and IL-27 in children with liver damage were significantly higher than in those without liver damage, while the expression of peripheral blood CD4+CD25+ regulatory T cells was lower than in those without liver damage (P<0.05). Plasma IL-17 and IL-27 levels were negatively correlated with the expression of peripheral blood CD4+CD25+ regulatory T cells (P<0.01). CONCLUSIONS: Immune imbalance mediated by CD4+CD25+ regulatory T cells and over-expression of IL-17 and IL-27 may be involved in the pathogenesis of liver damage in children with HCMV infection.

9.
J Dermatol Sci ; 91(3): 256-267, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29807809

RESUMO

BACKGROUND: Hyperthermia is an effective treatment against cancer and human papillomavirus (HPV) infection. Previous studies have shown that heat shock proteins are crucial to the action of hyperthermia. OBJECTIVES: To examine the effects of hyperthermia in combination with DNAJA4-deficiency on human keratinocytes and Condyloma acumunatum (CA) tissues. METHODS: HaCaT cells were subjected to 44°C (compared to 37°C) waterbath for 30min for stimulation. Foreskin or CA tissues obtained from patients undergoing circumcision or pathological examination were bisected and subjected to similar treatments. DNAJA4-knockout (KO) HaCaT cells were generated with CRISPR/Cas9 technology. mRNA and protein expressions were determined using rt-qPCR and western-blotting. Cell cycle distribution, apoptosis and senescence were analyzed by flow cytometry. RESULTS: DNAJA4 was induced in HaCaT cells, foreskin and CA tissues subjected to hyperthermia at both transcriptional and translational levels. NF-kB,3 was activated by hyperthermia in HaCaT cells, and further enhanced by DNAJA4-deficiency. Transcription of TNF-α4; IL-1B,5 TNFAIP36 and IL-87 were induced in HaCaT cells subjected to hyperthermia. DNAJA4-knockout promoted transcriptions of TNF-α and IL-1B, whereas decreased that of TNFAIP3 and IL-8. Reduced cell survival, proliferation and viability were demonstrated using flow cytometry and MTS assays. Furthermore, NF-kB inhibitors reversed most of the phenotypes observed. CONCLUSIONS: Hyperthermia reduced HaCaT cell proliferation and promoted cytokine expressions responsible for anti-viral activity, mainly through a NF-kB dependent pathway. DNAJA4-deficiency enhanced the activation of NF-kB by hyperthermia in HaCaT cells, indicating that DNAJA4 may be a promising therapeutic target for use in the treatment of cutaneous HPV infections.

10.
Leuk Res ; 69: 1-6, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29609040

RESUMO

Essential thrombocythemia (ET) is an uncommon chronic myeloproliferative disorder with no cure. Patients with ET are at risk of different complications, and currently there are no optimal prognostic standards to predict severe post-diagnosis complications such as thrombosis and hemorrhage. In this study, we retrospectively analyzed the full set of clinical data from 150 Chinese patients with ET enrolled from 2013 to 2016. We discovered that neutrophil-to-lymphocyte ratio (NLR), along with other known clinical parameters such as age, leukocyte count, incidence of thrombotic events is higher in patients with JAK2 V617F mutation. NLR is also higher in patients at high-risk stratification of thrombosis. Multivariate analysis showed that age (P = 0.001, 95% CI 1.023-1.089) and JAK2 V617F mutation (P = 0.003, 95% CI 1.837-21.035) were independent factors for thrombotic events, while age (P = 0.005, 95% CI 1.019-1.111) was the only predictive factor for hemorrhagic events at diagnosis. For future thrombotic events, multivariate analysis revealed NLR as the best predictive parameter (P < 0.001, 95% CI 1.173-1.486) when compared with other clinical parameters such as age (P = 0.037, 95% CI 1.004-1.126), thrombosis at diagnosis (P = 0.036, 95% CI 1.077-9.099) and WBC count (P = 0.047, 95% CI 1.001-1.109). Further ROC curve and Kaplan Meier analysis validated NLR as better prognostic marker for future thrombotic events and thrombosis-free survival. In summary, our data suggest that NLR parameter may possess great prognostic significance for future thrombosis in ET patients.

11.
Biochem Biophys Res Commun ; 499(3): 584-593, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29621546

RESUMO

Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors. However, the specific member of kallikrein family and its function in PDAC remain unexplored. In this study, by data mining of GEO datasets, we have identified KLK10 is upregulated gene in PDAC. We found that KLK10 was significantly overexpressed in tissues of pancreatic intraepithelial neoplasia (PanIN) and PDAC from Pdx1-Cre; LSL-KrasG12D/+ mice (KC) and Pdx1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ mice (KPC) by immunohistochemical analysis. Moreover, KLK10 is extremely elevated in the PDAC tissues, especially that from the PDAC patients with lymphatic and distant metastasis. Aberrant KLK10 expression is significantly correlated with poor prognosis and shorter survival by univariable and multivariable analysis. Functionally, knockdown of KLK10 observably inhibits invasion and metastatic phenotype of PDAC cells in vitro and metastasis in vivo. In addition, blockade of KLK10 attenuates epithelial-mesenchymal transition and activation of FAK-SRC-ERK signaling, which explains the mechanism of KLK10 in promoting metastasis. Collectively, KLK10 should be considered as a promising biomarker for diagnosis and potential target for therapy in PDAC.


Assuntos
Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Transição Epitelial-Mesenquimal/genética , Calicreínas/genética , Neoplasias Pancreáticas/genética , Regulação para Cima/genética , Adenocarcinoma/patologia , Animais , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Progressão da Doença , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Calicreínas/metabolismo , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Fenótipo , Prognóstico , Transdução de Sinais , Quinases da Família src/metabolismo
12.
Planta Med ; 84(14): 1013-1021, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29621808

RESUMO

Four new dolabellane-type diterpene alkaloids, glandulamines A - D (1:  - 4: ), together with twelve known compounds (5:  - 16: ), were isolated from the seeds of Nigella glandulifera using repeated column chromatography and semipreparative HPLC. The structures of 1:  - 16: were elucidated based on NMR data analysis, HRMS experiments and other spectroscopic interpretations. The absolute configuration of 5: was determined by single-crystal X-ray diffraction data for the first time. Compounds 10: and 12: showed human dihydroorotate dehydrogenase inhibitory activity with IC50 values of 61.1 ± 5.3 and 45.9 ± 3.0 µM, respectively. Molecular docking of the active compound 12: and positive control teriflunomide on the inhibitor-binding site of human dihydroorotate dehydrogenase was subsequently performed to visualize the interaction pattern. In addition, compounds 8: and 10: exhibited inhibitory effects against lipopolysaccharide-induced nitric oxide production with inhibition rates of 61 and 41%, respectively, at the concentration of 10 µM. Compounds 9: and 12: showed cytotoxic activities with cell viability varying from 29 ~ 57% at 100 µM against T98G, U87, U251, and GL261 glioma cancer cell lines. These data provide new insights on the pharmacologically active compounds of this plant widely used in folk medicine.


Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Citotoxinas/farmacologia , Diterpenos/farmacologia , Nigella/química , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores , Sementes/química , Alcaloides/química , Alcaloides/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Técnicas In Vitro , Óxido Nítrico/antagonistas & inibidores , Difração de Raios X
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(3): 204-208, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29530120

RESUMO

OBJECTIVE: To investigate the percentages of peripheral blood γδ T cells and regulatory T cells (Treg) and the expression of associated cytokines, interleukin 17 (IL-17) and transforming growth factor-ß1 (TGF-ß1), in infants with human cytomegalovirus (HCMV) infection. METHODS: Twenty-two infants with HCMV infection (HCMV group) and 22 healthy infants who underwent physical examination (control group) were enrolled in this study. The percentages of peripheral blood γδ T cells and Treg cells were determined by flow cytometry. The levels of IL-17 and TGF-ß1 in plasma were measured using ELISA. RESULTS: Compared with the control group, the HCMV group had significantly higher percentage of γδ T cells and IL-17 level (P<0.01) and significantly lower percentage of Treg cells and TGF-ß1 level (P<0.01). In the HCMV group, the percentage of γδ T cells was negatively correlated with the percentage of Treg cells and TGF-ß1 level (P<0.05), but positively correlated with IL-17 level (P<0.05); the percentage of Treg cells was positively correlated with TGF-ß1 level (P<0.05), but negatively correlated with IL-17 level (P<0.05); there was no correlation between IL-17 level and TGF-ß1 level (P>0.05). CONCLUSIONS: There is an imbalance between γδ T cells and Treg cells in the peripheral blood of infants with HCMV infection, and γδ T cells may be involved in the secretion of IL-17.


Assuntos
Citocinas/sangue , Infecções por Citomegalovirus/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/análise , Linfócitos T Reguladores/imunologia , Feminino , Humanos , Lactente , Interleucina-17/sangue , Masculino , Fator de Crescimento Transformador beta1/sangue
14.
Life Sci ; 195: 81-86, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29330116

RESUMO

AIM: To explore the role of tumor necrosis factor-alpha (TNF-α) on Staphylococcus aureus-induced necroptosis in alveolar epithelial cells. MAIN METHODS: The A549 alveolar epithelial cell line was pretreated with small interfering RNA (siRNA) against receptor interacting protein-3 (RIP3) and then stimulated by S. aureus, where some cells were pretreated with TNF-α or TNF-α with anti-TNF-α antibody simultaneously. A549 cell death was assessed using lactate dehydrogenase (LDH) leakage and flow cytometry analyses. The protein expressions of RIP1, RIP3, cleaved caspase-1, and cleaved caspase-8 were analyzed by western blot. KEY FINDINGS: S. aureus-induced LDH release was increased significantly by TNF-α. In addition, flow cytometry showed that TNF-α increased A549 cell apoptosis and necrosis in S. aureus-infected cell cultures. Levels of RIP3 and cleaved caspase-1 protein in A549 cells infected with S. aureus increased at 12 h post-infection, as shown by western blot. Significant additional increases in RIP3 expression were observed following the addition of TNF-α. Decreasing RIP3 levels by siRNA significantly suppressed the release of LDH induced by TNF-α and S. aureus. RIP3 siRNA also significantly suppressed A549 cell necrosis induced by S. aureus and TNF-α at 6 and 12 h post-infection as shown by flow cytometry analysis. SIGNIFICANCE: TNF-α enhances the damage of S. aureus on lung epithelial cells, and its mechanism is associated with RIP3 mediated necroptosis.


Assuntos
Morte Celular/efeitos dos fármacos , Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Células A549 , Células Epiteliais Alveolares , Caspase 8/genética , Caspase 8/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Necrose/induzido quimicamente , Necrose/patologia , Complexo de Proteínas Formadoras de Poros Nucleares/efeitos dos fármacos , Complexo de Proteínas Formadoras de Poros Nucleares/fisiologia , Proteínas de Ligação a RNA/efeitos dos fármacos , Proteínas de Ligação a RNA/fisiologia , Proteína Serina-Treonina Quinases de Interação com Receptores/efeitos dos fármacos
15.
ACS Appl Mater Interfaces ; 10(6): 5805-5811, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29361212

RESUMO

As a wise and profound teacher, nature provides numerous creatures with rich colors to us. To biomimic structural colors in nature as well as color changes responsive to environmental stimuli, there is a long way to go for the development of free-standing photonic films from natural polymers. Herein, a highly flexible, controllably iridescent, and multistimuli-responsive cellulose nanocrystal (CNC) film is prepared by simply introducing a small molecule as both plasticizer and hygroscopic agent. The presence of the additive does not block the self-assembly of CNC in aqueous solution but results in the enhancement of its mechanical toughness, making it possible to obtain free-standing iridescent CNC films with tunable structural colors. In response to environmental humidity and mechanical compression, such films can change structural colors smoothly by modulating their chiral nematic structures. Notably, the chromism is reversible by alternately changing relative humidity between 16 and 98%, mimicking the longhorn beetle Tmesisternus isabellae. This chromic effect enables various applications of the biofilms in colorimetric sensors, anticounterfeiting technology, and decorative coatings.

16.
Fitoterapia ; 125: 141-146, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29325928

RESUMO

Five new limonoids, swieteliacates A-E (1-5) and a tirucallane-type triterpenoid, swietesenin (6), together with four known compounds (7-10) were isolated from fruit of Swietenia macrophylla. Their structures were determined by spectroscopic analyses. The new compounds were tested in vitro for their cytotoxic effects against five human cancer cell lines. Compound 2 exhibited moderate cytotoxic activities against SW480 and HL-60 cancer cell lines with IC50 values of 30.6 and 32.9µM, respectively.


Assuntos
Limoninas/química , Meliaceae/química , Triterpenos/química , Linhagem Celular Tumoral , Frutas/química , Humanos , Limoninas/isolamento & purificação , Malásia , Estrutura Molecular , Triterpenos/isolamento & purificação
17.
Nanoscale Res Lett ; 12(1): 583, 2017 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-29110246

RESUMO

Three kinds of functional monomers, 4-vinylpridine(4-VP), 2-(allylthio)nicotinic acid(ANA), and 2-Acetamidoacrylic acid(AAA), were used to synthetize palladium(II) ion-imprinted polymeric nanospheres (Pd(II) IIPs) via precipitation-polymerization method in order to study the effects of different functional monomers on the adsorption properties of ion-imprinted materials. The results of UV spectra in order to study the interaction between template ion PdCl42- and functional monomers showed that there were great differences in structure after the template reacted with three functional monomers, 4-VP and ANA caused a large structural change, while AAA basically did not change. Further results on the adsorption performance of Pd(II) IIPs on Pd(II) confirmed 4-VP was the most promising candidate for the synthesis of Pd(II) IIPs with an adsorption capacity of 5.042 mg/g as compared with ANA and AAA. The influence of operating parameters on Pd(II) IIP's performance on Pd(II) adsorption was investigated. There was an increase in the adsorption capacity of Pd(II) IIPs at higher pH, temperature, and initial concentration of Pd(II). The results of multi-metal competitive adsorption experiments showed that Pd(II) IIPs had selectivity for Pd(II). An adsorption equilibrium could be reached at 180 min. Kinetic analysis showed that the adsorption test data fitted best to the pseudo-second order kinetic model, and the theoretical equilibrium adsorption capacity was about 5.085 mg/g. The adsorption isotherms of Pd(II) by Pd(II) IIPs agreed well with the Freundlich equation, suggesting a favorable adsorption reaction under optimal conditions. These results showed that Pd(II) IIPs have potential application in the removal of Pd(II) from aqueous solutions and may provide some information for the selection of functional monomers in the preparation of Pd(II) IIPs.

19.
Sci Rep ; 7(1): 4032, 2017 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-28642549

RESUMO

Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-ß1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs. Inhibition of FAK activation blocks the α-SMA and collagen expression, and inhibits the formation of stress fibers in TGF-ß1 treated HSCs. Furthermore, inhibition of FAK activation significantly reduces HSC migration and small GTPase activation, and induces apoptotic signaling in TGF-ß1 treated HSCs. Importantly, FAK inhibitor attenuates liver fibrosis in vivo and significantly reduces collagen and α-SMA expression in an animal model of liver fibrosis. These data demonstrate that FAK plays an essential role in HSC activation and liver fibrosis progression, and FAK signaling pathway could be a potential target for liver fibrosis.

20.
Sci Rep ; 7(1): 1359, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28465509

RESUMO

Growing evidence has shown that gut microbiome is a key factor involved in liver health. Therefore, gut microbiota modulation with probiotic bacteria, such as Saccharomyces boulardii, constitutes a promising therapy for hepatosis. In this study, we aimed to investigate the protective effects of S. boulardii on D-Galactosamine-induced liver injury in mice. Liver function test and histopathological analysis both suggested that the liver injury can be effectively attenuated by S. boulardii administration. In the meantime, S. boulardii induced dramatic changes in the gut microbial composition. At the phylum level, we found that S. boulardii significantly increased in the relative abundance of Bacteroidetes, and decreased the relative abundance of Firmicutes and Proteobacteria, which may explain the hepatic protective effects of S. boulardii. Taken together, our results demonstrated that S. boulardii administration could change the gut microbiota in mice and alleviate acute liver failure, indicating a potential protective and therapeutic role of S. boulardii.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/microbiologia , Galactosamina/toxicidade , Microbioma Gastrointestinal , Saccharomyces boulardii , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Células 3T3 BALB , Doença Hepática Induzida por Substâncias e Drogas/dietoterapia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Galactosamina/análogos & derivados , Camundongos , Probióticos
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