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1.
Cancer Immunol Immunother ; 73(8): 137, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833034

RESUMO

Tumor-infiltrating lymphocyte (TIL) deficiency is the most conspicuous obstacle to limit the cancer immunotherapy. Immune checkpoint inhibitors (ICIs), such as anti-PD-1 antibody, have achieved great success in clinical practice. However, due to the limitation of response rates of ICIs, some patients fail to benefit from monotherapy. Thus, novel combination therapy that could improve the response rates emerges as new strategies for cancer treatment. Here, we reported that the natural product rocaglamide (RocA) increased tumor-infiltrating T cells and promoted Th17 differentiation of CD4+ TILs. Despite RocA monotherapy upregulated PD-1 expression of TILs, which was considered as the consequence of T cell activation, combining RocA with anti-PD-1 antibody significantly downregulated the expression of PD-1 and promoted proliferation of TILs. Taken together, these findings demonstrated that RocA could fuel the T cell anti-tumor immunity and revealed the remarkable potential of RocA as a therapeutic candidate when combining with the ICIs.


Assuntos
Benzofuranos , Diferenciação Celular , Inibidores de Checkpoint Imunológico , Linfócitos do Interstício Tumoral , Receptor de Morte Celular Programada 1 , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/metabolismo , Camundongos , Animais , Benzofuranos/farmacologia , Benzofuranos/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Humanos , Diferenciação Celular/efeitos dos fármacos , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Feminino , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linhagem Celular Tumoral
2.
Am J Chin Med ; 52(3): 583-604, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716616

RESUMO

In recent years, due to advancements in medical conditions and the development of scientific research, the fundamental research of TCM antitumor treatments has progressed from the cellular level to the molecular and genetic levels. Previous studies have demonstrated the significant role of traditional Chinese medicine (TCM) in antitumor therapy through various mechanisms and pathways. Its mechanism of action is closely associated with cancer biology across different stages. This includes inhibiting tumor cell proliferation, blocking invasion and metastasis to surrounding tissues, inducing tumor cell apoptosis, inhibiting tumor angiogenesis, regulating immune function, maintaining genome stability, preventing mutation, and regulating cell energy metabolism. The use of TCM for eliciting antitumor effects not only has a good therapeutic effect and low side effects, it also provides a solid theoretical basis for clinical treatment and medication. This paper reviews the mechanism of the antitumor effects of TCM based on tumor characteristics. Through our review, we found that TCM not only directly inhibits tumors, but also enhances the body's immunity, thereby indirectly inducing an antitumor effect. This function aligns with the TCM theory of "strengthening the body's resistance to eliminate pathogenic factors". Furthermore, TCM will play a significant role in tumor treatment in clinical settings.


Assuntos
Apoptose , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Neovascularização Patológica/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Fitoterapia , Instabilidade Genômica , Metabolismo Energético/efeitos dos fármacos
3.
Free Radic Biol Med ; 219: 153-162, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38657753

RESUMO

The anemia of inflammation (AI) is characterized by the presence of inflammation and abnormal elevation of hepcidin. Accumulating evidence has proved that Rocaglamide (RocA) was involved in inflammation regulation. Nevertheless, the role of RocA in AI, especially in iron metabolism, has not been investigated, and its underlying mechanism remains elusive. Here, we demonstrated that RocA dramatically suppressed the elevation of hepcidin and ferritin in LPS-treated mice cell line RAW264.7 and peritoneal macrophages. In vivo study showed that RocA can restrain the depletion of serum iron (SI) and transferrin (Tf) saturation caused by LPS. Further investigation showed that RocA suppressed the upregulation of hepcidin mRNA and downregulation of Fpn1 protein expression in the spleen and liver of LPS-treated mice. Mechanistically, this effect was attributed to RocA's ability to inhibit the IL-6/STAT3 pathway, resulting in the suppression of hepcidin mRNA and subsequent increase in Fpn1 and TfR1 expression in LPS-treated macrophages. Moreover, RocA inhibited the elevation of the cellular labile iron pool (LIP) and reactive oxygen species (ROS) induced by LPS in RAW264.7 cells. These findings reveal a pivotal mechanism underlying the roles of RocA in modulating iron homeostasis and also provide a candidate natural product on alleviating AI.


Assuntos
Benzofuranos , Hepcidinas , Homeostase , Interleucina-6 , Ferro , Animais , Camundongos , Anemia/metabolismo , Anemia/genética , Anemia/tratamento farmacológico , Anemia/patologia , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Ferritinas/metabolismo , Ferritinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hepcidinas/efeitos dos fármacos , Hepcidinas/genética , Hepcidinas/metabolismo , Homeostase/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/genética , Inflamação/patologia , Interleucina-6/metabolismo , Interleucina-6/genética , Ferro/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Fígado/patologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Receptores da Transferrina/metabolismo , Receptores da Transferrina/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Benzofuranos/farmacologia
4.
Phytomedicine ; 128: 155333, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38518633

RESUMO

BACKGROUND: Targeting long non-coding RNAs (LncRNAs) is a novel and promising approach in cancer therapy. In our previous study, we investigated the effects of ailanthone (aila), the main active compound derived from the stem barks of Ailanthus altissima (Mill.) Swingle, on the growth of non-small cell lung cancer (NSCLC) cells. Although we observed significant inhibition of NSCLC cell growth of aila, the underlying mechanisms involving LncRNAs, specifically LncRNA growth arrest specific 5 (GAS5), remain largely unknown. METHODS: To further explore the impact of aila on NSCLC, we performed a series of experiments. Firstly, we confirmed the inhibitory effect of aila on NSCLC cell growth using multiple assays, including MTT, wound healing, transwell assay, as well as subcutaneous and metastasis tumor mice models in vivo. Next, we utilized cDNA microarray and RT-QPCR to identify GAS5 as the primary target of aila. To verify the importance of GAS5 in aila-induced tumor inhibition, we manipulated GAS5 expression levels by constructing GAS5 over-expression and knockdown NSCLC cell lines. Furthermore, we investigated the upstream and downstream signaling pathways of GAS5 through western blot and RT-QPCR analysis. RESULTS: Our results showed that aila effectively increased GAS5 expression, as determined by microarray analysis. We also observed that aila significantly enhanced GAS5 expression in a dose- and time-dependent manner across various NSCLC cell lines. Notably, over-expression of GAS5 led to a significant suppression of NSCLC cell tumor growth; while aila had minimal inhibitory effect on GAS5-knockdown NSCLC cells. Additionally, we discovered that aila inhibited ULK1 and autophagy, and this inhibition was reversed by GAS5 knockdown. Moreover, we found that aila up-regulated GAS5 expression by suppressing UPF1-mediated nonsense-mediated mRNA decay (NMD). CONCLUSION: In summary, our findings suggest that aila promotes GAS5 expression by inhibiting UPF1-mediated NMD, leading to the repression of ULK1-mediated autophagy and subsequent inhibitory effects on NSCLC cells. These results indicate that aila is a potent enhancer of GAS5 and holds promising potential for application in NSCLC therapy. However, our research is currently focused only on NSCLC. It remains to be determined whether aila can also inhibit the growth of other types of tumors through the UPF1/GAS5/ULK1 signaling pathway. In future studies, we can further investigate the mechanisms by which aila suppresses other types of tumors and potentially broaden the scope of its application in cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , RNA Longo não Codificante , Transdução de Sinais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , RNA Longo não Codificante/genética , Humanos , Animais , Neoplasias Pulmonares/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos , Camundongos Nus , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Transativadores/genética , Transativadores/metabolismo , Ailanthus/química , Antineoplásicos Fitogênicos/farmacologia , Camundongos Endogâmicos BALB C , Quassinas/farmacologia , RNA Helicases/metabolismo
5.
J Leukoc Biol ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456763

RESUMO

Immune evasion by cancer cells poses a significant challenge for natural killer (NK) cell-based immunotherapy. Pyroptosis, a newly discovered form of programmed cell death, has shown great potential for enhancing the antitumor immunity of NK cells. Consequently, targeting pyroptosis has become an attractive strategy for boosting NK cell activity against cancer. In this study, various assays were conducted, including NK cell cytotoxicity assays, flow cytometry, xenograft tumor models, real-time PCR, and ELISA to assess NK cell-mediated cell killing, as well as gene and protein expressions. The results indicated that Euphohelioscopin A (Eupho-A), a potential pyroptosis activator, enhances NK cell-mediated lysis of tumor cells, resulting in inhibiting tumor growth that could be reversed by NK cell depletion. Furthermore, we found that Eupho-A significantly enhanced IFN-γ production in NK cells and synergistically up-regulated GSDME with IFN-γ in cancer cells. Eupho-A also increased the cleavage of GSDME, promoting GZMB-induced pyroptosis, which could be reversed by GSDME knockdown and IFN-γ blockade. Overall, the findings suggested that Eupho-A enhanced NK cell-mediated killing of cancer cells by triggering pyroptosis, making Eupho-A a promising pyroptosis activator with great potential for using in NK cell-based cancer immunotherapy.

6.
Pest Manag Sci ; 79(12): 5044-5052, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37556562

RESUMO

BACKGROUND: Periplocoside P (PSP) is a major component of Periploca sepium Bunge known for its potent insecticidal activity. V-Type adenosine triphosphatase (V-ATPase), which is widely distributed in the cytoplasmic membranes and organelles of eukaryotic cells, plays a crucial role in synaptic excitability conduction. Previous research has shown that PSP targets the apical membrane of goblet cells in the insect midgut. However, the effects of PSP on synaptic transmission at the neuromuscular junction are often overlooked. RESULTS: The bioassay revealed that Drosophila adults with different genetic backgrounds showed varying levels of susceptibility to PSP in the order: parats1 > parats1 ;DSC1-/- ≈ w1118 > DSC1-/- . Intracellular electrode recording demonstrated that PSP, similar to bafilomycin A1, had an impact on the amplitude of the excitatory junction potential (EJP) and accelerated excitability decay. Furthermore, the alteration in EJP amplitude is concentration-dependent. Another surprising discovery was that the knockout DSC1 channel showed insensitivity to PSP. CONCLUSION: Our findings confirm that PSP can influence synaptic transmission at the neuromuscular junction of Drosophila larvae by targeting V-ATPase. These results provide a basis for investigating the mechanism of action of PSP and its potential application in designing novel insecticides. © 2023 Society of Chemical Industry.


Assuntos
Drosophila melanogaster , Inseticidas , Animais , Adenosina Trifosfatases , Inseticidas/farmacologia , Drosophila , Transmissão Sináptica , Junção Neuromuscular
7.
BMC Med Imaging ; 22(1): 51, 2022 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305577

RESUMO

OBJECTIVE: To investigate and verify the efficiency and effectiveness of a nomogram based on radiomics labels in predicting the treatment of lumbar disc herniation (LDH). METHODS: By reviewing medical records that were analysed over the past three years, clinical and imaging data of 200 lumbar disc patients at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were obtained. The collected cases were randomly divided into a training group (n = 140) and a testing group (n = 60) at a ratio of 7:3. Two radiologists with experience in reading orthopaedics images independently segmented the ROIs. The whole intervertebral disc with the most obvious protrusion in the sagittal plane T2WI lumbar MRI as a mask (ROI) is sketched. The LASSO (Least Absolute Shrinkage And Selection Operator) algorithm was used to filter the features after extracting the radiomics features. The multivariate logistic regression model was used to construct a quantitative imaging Rad­Score for the selected features with nonzero coefficients. The radiomics labels and nomogram were evaluated using the receiver operating characteristic curve (ROC) and the area under the curve (AUC). The calibration curve was used to evaluate the consistency between the nomogram prediction and the actual treatment plan. The DCA decision curve was used to evaluate the clinical applicability of the nomogram. RESULT: Following feature extraction, 11 radiomics features were used to construct the radiomics label for predicting the treatment plan of LDH. A nomogram was then constructed. The AUC was 0.93 (95% CI: 0.90-0.97), with a sensitivity of 89%, a specificity of 91%, a positive predictive value of 92.7%, a negative predictive value of 89.4%, and an accuracy of 91%. The calibration curve showed that there was good consistency between the prediction and the actual observation. The DCA decision curve analysis showed that the nomogram of the imaging group has great potential for clinical application when the risk threshold is between 5 and 72%. CONCLUSION: A nomogram based on radiomics labels has good predictive value for the treatment of LDH and can be used as a reference for clinical decision-making.


Assuntos
Deslocamento do Disco Intervertebral , Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/terapia , Imageamento por Ressonância Magnética/métodos , Nomogramas , Estudos Retrospectivos
8.
Ann Transl Med ; 10(24): 1359, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36660626

RESUMO

Background: As a surrogate for the breast tumor bed, individual fiducial markers frequently move during radiotherapy. This study aimed to classify the motions and calculate the individualized target margin. Methods: The mammary basal diameters (D) and heights (H) were measured to represent breast sizes for 15 patients after breast-conserving surgery. The clinical target volume (CTV) was divided into 4 quadrants by a coordinate system with the center of mass of the tumor bed as the origin. The lateral, anteroposterior, and craniocaudal motions of markers were calculated (MLR, MAP, MSI) based on the difference of the setup errors between the spine matching and the fiducial markers matching. The distances between markers and the innermost, foremost, and uppermost borders of CTV (DSLR, DSAP, DSSI) were recorded. Results: In the first quadrant, MAP was strongly correlated with D×H (r>0.80) when D×H <99.89 cm2. Both MLR and MAP were positively linearly related to DSLR, DSAP, DSSI (r>0.85, R2>0.75). MSI was also positively linearly correlated with DSAP and DSLR (r>0.90, R2>0.80). In the fourth quadrant with D×H <90.71 cm2, only MLR and DSLR showed a linear positive correlation (r>0.90, R2>0.75), whereas the others showed linear negative correlations (r>-0.90, R2>0.80). The planning target volume (PTV) margin varied significantly between the first and fourth quadrant (P<0.05), and the largest margin was 12.4 mm in the craniocaudal direction of the first quadrant with D×H ≥99.89 cm2. Conclusions: Fiducial motion is susceptible to breast size and fiducial position, and the individualized PTV margins should take the above factors into account.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34444367

RESUMO

Residential sprawl constitutes a main part of urban sprawl which poses a threat to the inhabitant environment and public health. The purpose of this article is to measure the residential sprawl at a micro-scale using a case study of Hangzhou city. An integrated sprawl index on each 1 km × 1 km residential land cell was calculated based on multi-dimensional indices of morphology, population density, land-use composition, and accessibility, followed by a dynamic assessment of residential sprawl. Furthermore, the method of GeoDetector modeling was applied to investigate the potential effects of location, urbanization, land market, and planning policy on the spatial variation of residential sprawl. The results revealed a positive correlation between CO2 emissions and residential sprawl in Hangzhou. There has been a remarkable increase of sprawl index on residential land cells across the inner suburb and outer suburb, and more than three-fifths of the residential growth during 2000-2010 were evaluated as dynamic sprawl. The rapid development of the land market and urbanization were noted to impact the spatiotemporal distribution of residential sprawl, as q-statistic values of population growth and land price ranked highest. Most notably, the increasing q-statistic values of urban planning and its significant interactions with other factors highlighted the effects of incremental planning policies. The study derived the policy implication that it is necessary to transform the traditional theory and methods of incremental planning.


Assuntos
Planejamento de Cidades , Urbanização , Cidades , Densidade Demográfica , Crescimento Demográfico
10.
Front Physiol ; 12: 619816, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643066

RESUMO

Odorant binding proteins (OBPs) play a key role in the olfactory recognition of insects, whose functions have been extensively studied in adult insects but rarely in larvae. In this study, one OBP (SlitOBP11) with high expression in larval antenna but low expression in adult antenna of Spodoptera litura was screened by RNA-seq and verified by quantitative real-time PCR. Furthermore, the function of SlitOBP11 was explored by analysis of the expression patterns and prokaryotic expression of proteins as well as assays of competitive binding. Competitive binding assay demonstrated that SlitOBP11 had high binding affinity to all four female sex pheromone components, but exhibited almost no binding affinity to plant volatiles except for a low affinity to Phenylacetaldehyde and Phenethyl acetate. Homology modeling and molecular docking implied that the shape of these four sex pheromones were linear, which were appropriate for the binding channel of SlitOBP11 and the amino acid residue Asn99 of SlitOBP11 might play an important role in binding. Taken together, our results indicate that SlitOBP11 may be involved in the perception of female sex pheromones by S. litura larvae, and OBPs in the larvae of S. litura play an important role in the olfactory perception process.

11.
Front Genet ; 12: 611476, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33719334

RESUMO

Insects are behaviorally and physiologically affected by different light conditions, including photoperiod, light intensity, and spectrum. Light at night has important influences on nocturnal insects, including most moth species. Moth copulation and mating usually occur at night. Although a few studies examine changes in insect mating under artificial light at night, detailed influences of light, such as that of monochromatic light, on moth mating remain largely unknown. In this study, on the basis of long-term insects rearing experience, dim red light (spectrum range: 610-710nm, with a peak at 660nm; 2.0 Lux) during scotophase was hypothesized to enhance mating in the yellow peach moth, Conogethes punctiferalis. To test the hypothesis, the mating of moths under dim red, blue, and white lights during scotophase was observed. Under the dim red light, the enhancement of mating in C. punctiferalis was observed. In addition, the electroantennografic response of males against the female sex pheromone increased with red light treatment during scotophase. In an analysis of the differentially expressed genes in the antennae of males under red light and dark conditions, the expression levels of two odorant-binding protein (OBP) genes, CpunOBP2 and CpunPBP5, were up-regulated. Two genes were then expressed in Escherichia coli, and the recombinant proteins showed strong binding to female pheromone components in fluorescence-binding assays. Thus, the results of this study indicated that dim red light at night enhanced the mating of C. punctiferalis. One of the mechanisms for the enhancement was probably an increase in the antennal sensitivity of males to the female sex pheromone under red light that was caused by increases in the expression levels of pheromone-binding protein genes in male antennae.

12.
World J Gastroenterol ; 23(29): 5333-5344, 2017 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-28839433

RESUMO

AIM: To investigate the capability of salvianolic acid B (Sal B) to protect hepatocytes from hydrogen peroxide (H2O2)/carbon tetrachloride (CCl4)-induced lysosomal membrane permeabilization. METHODS: Cell Counting Kit-8 assay was used to measure cell viability. Apoptosis and death were assayed through flow cytometry. BrdU incorporation was used to detect cell proliferation. Serum alanine aminotransferase activity and liver malondialdehyde (MDA) content were measured. Liver histopathological changes were evaluated using hematoxylin-eosin staining. Lysosomal membrane permeability was detected with LysoTracker Green-labeled probes and acridine orange staining. The levels of protein carbonyl content (PCC), cathepsins (Cat)B/D, and lysosome-associated membrane protein 1 (LAMP1) were evaluated through western blotting. Cytosol CatB activity analysis was performed with chemiluminescence detection. The mRNA level of LAMP1 was evaluated through quantitative real-time polymerase chain reaction. RESULTS: Results indicated that H2O2 induced cell injury/death. Sal B attenuated H2O2-induced cell apoptosis and death, restored the inhibition of proliferation, decreased the amount of PCC, and stabilized the lysosome membrane by increasing the LAMP1 protein level and antagonizing CatB/D leakage into the cytosol. CCl4 also triggered hepatocyte death. Furthermore, Sal B effectively rescued hepatocytes by increasing LAMP1 expression and by reducing lysosomal enzyme translocation to the cytosol. CONCLUSION: Sal B protected mouse embryonic hepatocytes from H2O2/CCl4-induced injury/death by stabilizing the lysosomal membrane.


Assuntos
Benzofuranos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Membranas Intracelulares/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Apoptose/efeitos dos fármacos , Benzofuranos/uso terapêutico , Western Blotting , Tetracloreto de Carbono/toxicidade , Catepsina A/metabolismo , Catepsina B/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citosol/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Citometria de Fluxo , Hepatócitos , Humanos , Peróxido de Hidrogênio/toxicidade , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Proteínas de Membrana Lisossomal/metabolismo , Lisossomos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Carbonilação Proteica/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Salvia miltiorrhiza/química , Transdução de Sinais
13.
J Cancer ; 7(13): 1877-1887, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27698928

RESUMO

Cistanche tubulosa phenylethanoid glycosides (CTPG) have been shown various biological activities including anti-allergy, hepatoprotective activity and bone regeneration. However, the anti-tumor activity of CTPG needs to be investigated. CTPG was used to treat B16-F10 cells both in vitro and in vivo. We found that CTPG dramatically changed the morphology of B16-F10 cells, and significantly reduced the viability of B16-F10 cells in a dose-dependent and time-dependent manner, which might be mediated by CTPG-induced apoptosis and cell cycle arrest. After CTPG treatment, the expressions of BAX and BCL-2 were up-regulated and down-regulated, respectively. Moreover, mitochondrial membrane potential was reduced and ROS generation was increased. Consequently, the levels of cytochrome c and cleaved-caspase-3 and -9 were up-regulated by CTPG treatment but not for cleaved-caspase-8. We further observed that CTPG significantly inhibited the tumor growth in vivo and improved the survival rate of tumor mice. We also observed that CTPG promoted the proliferation of splenocytes and increased the proportions of CD4+ and CD8+ T cells in spleens of tumor mice. The results showed that CTPG induced the apoptosis of B16-F10 cells through mitochondria-dependent pathway, suggesting that CTPG could be a potential candidate for treatment of cancer.

14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 32(10): 1331-1335, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-27667457

RESUMO

Objective To construct a DNA contraception vaccine targeting canine zona pellucida 3 (CZP3) antigen and assess the immunological efficacy and contraceptive effect of the vaccine. Methods The CZP3 gene was amplified from total RNA of canine ovary by reverse transcription PCR and analyzed by bioinformatics, such as ProtScale, TMHMM, Signal P, InterProScan, PREDICT PROTEIN, homology modeling, etc. The constructed DNA vaccine pcDNA-CZP3 was used to vaccinate mice, and then its immune effect and contraceptive effect were evaluated in the mice. Results The CZP3 gene had 426 amino acids with two hydrophobic regions at its N-terminal and C-terminal, respectively. The top 22 amino acids at the N-terminal of the CZP3 was the signal peptide and there was a transmembranous helix from extracellular to intracellular at the C-terminal. CZP3 also had 8 B cell epitopes. The DNA contraception vaccine pcDNA3-CZP3 induced high levels of antibody and lower average litter size of mouse compared with the blank and negative control groups significantly. Conclusion The canine contraception DNA vaccine pcDNA-CZP3 has been successfully constructed and it can reduce the mouse fertility remarkably.


Assuntos
Anticoncepção Imunológica/veterinária , Cães/fisiologia , Fertilidade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Vacinas Anticoncepcionais/imunologia , Vacinas de DNA/imunologia , Glicoproteínas da Zona Pelúcida/imunologia , Zona Pelúcida/imunologia , Animais , Anticorpos/imunologia , Anticoncepção Imunológica/instrumentação , Anticoncepção Imunológica/métodos , Cães/imunologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Vacinação , Vacinas Anticoncepcionais/administração & dosagem , Vacinas Anticoncepcionais/genética , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética , Glicoproteínas da Zona Pelúcida/administração & dosagem , Glicoproteínas da Zona Pelúcida/genética
15.
Vaccine ; 34(31): 3568-75, 2016 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-27211038

RESUMO

Our previous study reported that the combination of Pleurotus ferulae water extract (PFWE) and CpG (PFWE+CpG) enhanced the maturation and function of dendritic cells (DCs). Here, we investigated the effects of PFWE+CpG on the immune responses and antitumor efficacy of DC-based vaccine. We observed that all of HPV E6 and E7 peptides pulsed DCs (HPV-immature DCs, HPV+PFWE-, +CpG- or +PFWE+CpG-DCs) induced antigen-specific CD8(+) T cell responses and HPV+PFWE+CpG-DCs induced highest level of CD8(+) T cell responses. The antitumor efficacy of HPV-DCs vaccines was evaluated in TC-1 tumor mouse model. The early therapeutic study showed that HPV+PFWE-, +CpG- and +PFWE+CpG-DCs greatly inhibited tumor growth. Moreover, HPV+PFWE+CpG-DCs controlled tumor growth at a faster rate compared to other groups. These three groups induced HPV-specific CD8(+) T cell responses and significantly decreased the frequencies of induced regulatory T cells (iTregs: CD4(+)CD25(-)Fopx3(+)). However, only HPV+PFWE+CpG-DCs significantly decreased the frequency of natural Tregs (nTregs: CD4(+)CD25(+)Fopx3(+)). Furthermore, HPV+PFWE+CpG-DCs also significantly inhibited tumor growth in the late therapeutic study. The results showed that PFWE+CpG enhanced the immune responses and antitumor efficacy of DC-based vaccine, suggesting that PFWE+CpG might be the potential candidate for the generation of clinical-grade mature DCs.


Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Neoplasias/prevenção & controle , Oligodesoxirribonucleotídeos/imunologia , Infecções por Papillomavirus/prevenção & controle , Pleurotus/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/virologia , Papillomaviridae , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/imunologia
16.
Vaccine ; 33(16): 1923-33, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25748337

RESUMO

Dendritic cells (DCs) play important roles in the regulation of immune system, which link innate and adaptive immune responses. Mature DCs produced interleukin (IL)-12 promote optimal type 1 T helper (Th1) cells and cytotoxic T lymphocytes. The extracts of traditional herbal medicines have been shown to enhance immune responses through promoting the maturation and cytokine production of DCs. Here, we investigated the effects of Pleurotus ferulae water extract (PFWE) on the maturation and function of bone marrow-derived DCs (BM-DCs). Upon PFWE treatment, BM-DCs dose-dependently upregulated the expression of CD40, CD80, CD86 and MHC II and increased the production of IL-12, IL-6 and tumor necrosis factor (TNF)-α but not for IL-10, which is mediated by TLR4 signaling pathway, at least partially. The production of prostaglandin E2 (PGE2) in BM-DCs was decreased by the treatment of PFWE. Moreover, PFWE treatment decreased the expression of active caspase-3 but increased the expression of CCR7. PFWE treated DCs enhanced the proliferation of allogenic CD8(+) T cells and the capacity of antigen presenting to autologous CD8(+) T cells. The combination of PFWE and CpG-ODN further enhanced the maturation and function of murine BM-DCs. The results showed that PFWE could enhance the maturation and function of DCs through TLR4 signaling pathway and has additive effect when combined with CpG-ODN, suggesting that PFWE alone or combined with CpG-ODN could be used to enhance the immune responses.


Assuntos
Produtos Biológicos/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Pleurotus/química , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Animais , Apresentação de Antígeno/imunologia , Apoptose/efeitos dos fármacos , Células da Medula Óssea/citologia , Diferenciação Celular/efeitos dos fármacos , Citocinas/biossíntese , Células Dendríticas/citologia , Dinoprostona/biossíntese , Feminino , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Camundongos , Fenótipo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
17.
J Mater Chem B ; 3(6): 1116-1124, 2015 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32261990

RESUMO

Polyaniline (PANI) microtubes are becoming greatly significant electrochemical materials owing to their large geometric surface area, high conductivity and ideal electrocatalytic activity. In this work, using glucose oxidase (GOx) as a model redox protein, a direct electron transfer strategy based on PANI microtubes was developed for fabricating sensitive biosensors. There is a strong electrostatic interaction between the positively charged PANI microtubes and negatively charged GOx, which promotes the immobilization of GOx on the PANI microtube surface. The immobilized GOx displayed a pair of well-defined quasi-reversible redox peaks with a potential of -0.39 V (vs. SCE) and an ideal electron transfer rate constant (ks) of 3.0 s-1 in PBS solution (0.1 M, pH = 5.5) on the PANI microtubes instead of a bare glass carbon electrode (GCE). The amperometric response of the GOx/PANI microtube modified electrode was linearly proportional to the concentration of glucose in the range of 4.0 µM to 0.80 mM. The glucose detection limit was 0.8 µM at a signal-to-noise ratio of 3, which was better than those reported for the GOx/PANI film (1 mM) and GOx/PANI nanowire (50 µM). The advantages might be attributed to the PANI microtubes' large geometric surface for carrying enzyme (GOx) and efficient electrocatalytic activity to facilitate the direct electron transfer of GOx, as well as an efficient GOx biocatalyst reaction on the microtube surface. A promising application of PANI microtube-based biosensors was offered.

18.
Analyst ; 139(14): 3622-8, 2014 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-24886910

RESUMO

In this article, a bare glassy carbon electrode (GCE) surface was directly activated by a simple in situ chemical method, which was characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Based on these results, it was found that oxygen-containing functional groups at the modified GCE surface were enhanced with a low damage to the surface state. Hence, the modified GCE exhibited an excellent performance, such as the negatively charged surface, good reproducibility and high selectivity. The resulting electrode was applied as a sensitive sensor for detection of antioxidant tertiary butyl hydroquinone (TBHQ), and a good linear relationship was obtained between the oxidation peak current and the concentration in a broad range of 1.0 µM-1.1 mM, with detection limits of 67 nM (S/N = 3) by DPV. Electrochemical parameters of TBHQ on the resulting GCE were also investigated, suggesting that the modified GCE could promote electron transfer kinetics towards the electrochemical reaction of TBHQ. Besides, the present method was used for determination of TBHQ in jatropha biodiesel with recovery ranging from 95.2% to 103.2%.

19.
J Mater Chem B ; 2(26): 4122-4129, 2014 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32261744

RESUMO

An easy and convenient method for the synthesis of polyaniline (PANI) microtubes was developed using polystyrene (PS) electrospun microfibers as a template. The diameter range of these microtubes was from 0.63 to 2.93 µm. This accuracy was achieved by tuning the template microfiber's diameter. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to study the effect of these microtubes' diameters on their electroactivity. When the diameter is 1.43 µm, the PANI microtube exhibited the maximum electroactivity and a distinguished electrocatalytic oxidation of ascorbic acid (AA). Herein, the PANI microtube was fabricated into an amperometric AA sensor. At the working potential of 0.4 V (vs. SCE), the oxidation current was significantly enhanced by the addition of a low concentration of AA but no such current was observed with other selected small molecules. The AA detection limit was 0.28 µM at the signal-to-noise ratio of 3. A linear relationship was demonstrated between the oxidation current enhancement and the AA concentration ranging from 5.0 µM to 4.7 mM. The detection limit was better than a reported PANI nanotube (1.0 µM), nanofiber (1.7 µM) and nanoparticle (8.3 µM). The high sensitivity could be attributed to the PANI microtube's high conductivity, high electroactivity for the AA electrocatalytic oxidation, as well as its high surface-to-volume ratio resulting in an efficient interaction between the microtube and the AA molecule. A promising application of the PANI microtube-based sensor was offered.

20.
Analyst ; 138(20): 6171-6, 2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-23971074

RESUMO

Ruthenium nanoparticle tris(2,2'-bipyridyl)ruthenium(II) bis(hexafluorophosphate) (Ru(bpy)3(PF6)2, RuNP) was self-assembled on polystyrene (PS) electrospun microfibers. The formation of RuNP is attributed to the sulfonated PS (SPS) microfibers' high adsorptive capability of 94% for Ru(bpy)3(2+), as well as the strong interaction between the Ru(bpy)3(2+) and ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate, BMIMPF6). The RuNP/SPS microfibers exhibited an enhanced electrochemiluminescence (ECL) emission, 2.3 times higher than that from Ru(bpy)3(2+)/SPS microfibers and 6.6 times higher than that from Ru(bpy)3(2+)/SPS continuous thin films. It is worthy of note that, as a result of the hydrophobic nature of the RuNP, the transfer of water-insoluble α-naphthol is accelerated, and thus the α-naphthol ECL quenching efficiency is enhanced. An ECL sensor based on the RuNP/SPS microfibers was fabricated and used to detect low concentrations of α-naphthol. The detection limit was of 1.0 nM (S/N > 3), and the linear response ranged from 0 to 18 µM. This sensor has been successfully applied to measure the α-naphthol content in pesticide carbaryl samples. Our work provides a very simple and cost-effective method to fabricate RuNP on polymer microfibers with great potential in the field of chemo/biosensors.

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