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1.
Plant Commun ; : 100857, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38433446

RESUMO

The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing species. However, the mechanisms that regulate this process in plants remain largely unknown. Here, we find that the rice (Oryza sativa L.) protein RETINOBLASTOMA RELATED 1 (RBR1) is essential to the transition from mitosis to meiosis. Loss of RBR1 function results in hyper-proliferative sporogenous-cell-like cells (SCLs) in the anther locules during early stages of reproductive development. These hyper-proliferative SCLs are unable to initiate meiosis, eventually stagnating and degrading at late developmental stages to form pollen-free anthers. These results suggest that RBR1 acts as a gatekeeper of entry into meiosis. Furthermore, cytokinin content is significantly increased in rbr1 mutants, whereas the expression of type-B response factors, particularly LEPTO1, is significantly reduced. Given the known close association of cytokinins with cell proliferation, these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin pathway. Using a genetic strategy, the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been confirmed. In summary, we reveal a unique role of RBR1 in the initiation of meiosis; our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.

2.
Nano Lett ; 23(3): 757-764, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36648291

RESUMO

Effective delivery of the CRISPR-Cas9 components is crucial to realizing the therapeutic potential. Although many delivery approaches have been developed for this application, oral delivery has not been explored due to the degradative nature of the gastrointestinal tract. For this issue, we developed a series of novel phenylboronic acid (PBA)-functionalized chitosan-polyethylenimine (CS-PEI) polymers for oral CRISPR delivery. PBA functionalization equipped the polyplex with higher stability, smooth transport across the mucus, and efficient endosomal escape and cytosolic unpackaging in the cells. From a library of 12 PBA-functionalized CS-PEI polyplexes, we identified a formulation that showed the most effective penetration in the intestinal mucosa after oral gavage to mice. The optimized formulation performed feasible CRISPR-mediated downregulation of the target protein and reduction in the downstream cholesterol. As the first oral CRISPR carrier, this study suggests the potential of addressing the needs of both local and systemic editing in a patient-compliant manner.


Assuntos
Ácidos Borônicos , Quitosana , Animais , Camundongos , Polímeros , Técnicas de Transferência de Genes
3.
Nat Prod Res ; 37(19): 3245-3252, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35437081

RESUMO

Resina Draconis (RD), also known as 'dragon's blood', contains a broad range of natural compounds, such as flavonoids, stilbenes and dihydrochalcones. It is clinically used to enhance blood circulation. However, the major components of RD suffer from relatively poor water solubility. Glycosylation is a critical determinant for modulating solubility and improving bioavailability and bioactivity of natural products. Herein, we report a novel method to efficiently synthesize glycosidic derivatives of the major polyphenols in RD using a microbial glycosyltransferase, i.e., YjiC1. Solubility test showed that the synthetic glycosidic derivatives displayed higher water solubility than the raw materials. This research sheds light on the structural modification of natural products for higher water solubility, which is important for innovative drug discovery.

4.
Med Biol Eng Comput ; 60(6): 1613-1626, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35397109

RESUMO

Gas embolism is a potentially serious complication of hysteroscopic surgery. It is particularly necessary to monitor bubble parameters in hysteroscopic images by computer vision method for helping develop automatic bubble removal devices. In this work, a framework combining a deep edge-aware network and marker-controlled watershed algorithm is presented to extract bubble parameters from hysteroscopy images. The proposed edge-aware network consists of an encoder-decoder architecture for bubble segmentation and a contour branch which is supervised by edge losses. The post-processing method based on marker-controlled watershed algorithm is used to further separate bubble instances and calculate size distribution. Extensive experiments substantiate that the proposed model achieves better performance than some typical segmentation methods. Accuracy, sensitivity, precision, Dice score, and mean intersection over union (mean IoU) obtained for the proposed edge-aware network are observed as 0.859 ± 0.017, 0.868 ± 0.019, 0.955 ± 0.005, 0.862 ± 0.005, and 0.758 ± 0.007, respectively. This work provides a valuable reference for automatic bubble removal devices in hysteroscopic surgery.


Assuntos
Aprendizado Profundo , Redes Neurais de Computação , Algoritmos , Processamento de Imagem Assistida por Computador/métodos
5.
Biochem Genet ; 60(6): 2106-2119, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35254597

RESUMO

This study aims to investigate the specific mechanism of miR-139-5p regulating hepatocellular carcinoma (HCC). Bioinformatic approaches was utilized to observe miR-139-5p level in HCC and unearth its target mRNA. Next, miR-139-5p and enabled homolog (ENAH) levels in HCC cell lines and normal liver cell line were evaluated with qRT-PCR. ENAH protein level was assessed by Western blot. The cell viability, migratory and invasive capacities of HepG2 cells was observed by cell functional assays. The binding of these two genes was proved through dual-luciferase method. Xenograft nude mouse model was prepared to identify the role of miR-139-5p in vivo. Poorly expressed miR-139-5p in HCC hindered the phenotypes of cancer cells. ENAH was at high level in HCC and it is a downstream target of miR-139-5p. Additionally, ENAH could reverse the suppressive impacts of miR-139-5p on HCC cell behaviors. Likewise, miR-139-5p was determined to perform tumor-suppressing function in vivo. MiR-139-5p hampered HCC cell processes by mediating ENAH, and miR-139-5p/ENAH is hopefully to be the possible target for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Linhagem Celular Tumoral , Camundongos Nus , Movimento Celular/genética , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo
6.
Bol. latinoam. Caribe plantas med. aromát ; 20(5): 515-523, sept. 2021. ilus
Artigo em Inglês | LILACS | ID: biblio-1369061

RESUMO

To explore a new underlying molecular mechanism of Huangkui Extract Powder (HKEP) in the alleviation of diabetic nephropathy (DN). Murine immortalized podocytes were divided into (i) normal glucose (NG, 5.6 mM), (ii) NG + HKEP (0.45 g/L), (iii) HG, and (iv) HG + HKEP (0.45 g/L) groups. MTT assay and flow cytometry were used to detect the podocyte proliferation, apoptosis and cell cycle. Cell viability was inhibited, and apoptosis increased in(iii) HG group compared with (i) NG group (p<0.05). mRNA and protein expression of nephrin and podocin significantly decreased in (iii) HG group compared with (i) NG group (p<0.05). When compared with (iii) HG group, (iv) HG + HKEP group had higher cell viability, lower apoptotic rate and higher mRNA and protein expression of nephrin and podocin (p<0.05). HKEP can attenuate HG-induced podocyte damage, which may be one of the mechanisms of HKEP for attenuating DN.


Explorar un nuevo mecanismo molecular subyacente del extracto del polvo de Huangkui (HKEP) en el alivio de la nefropatía diabética (ND). Los podocitos murinos inmortalizados se dividieron en (i) grupos de glucosa normal (NG, 5,6 mM), (ii) NG + HKEP (0,45 g/L), (iii) HG y (iv) HG + HKEP (0,45 g/L). Se utilizaron el ensayo MTT y la citometría de flujo para detectar la proliferación de podocitos, la apoptosis y el ciclo celular. La viabilidad celular se inhibió y la apoptosis aumentó en el grupo (iii) HG en comparación con el grupo (i) NG (p<0,05). La expresión de ARNm y proteínas de nefrina y podocina disminuyó significativamente en el grupo (iii) HG en comparación con el grupo (i) NG (p<0,05). En comparación con el grupo (iii) HG, el grupo (iv) HG + HKEP tuvo una mayor viabilidad celular, una tasa de apoptosis más baja y una expresión de ARNm y proteínas más altas de nefrina y podocina (p<0,05). HKEP puede atenuar el daño de los podocitos inducido por HG, que puede ser uno de los mecanismos de HKEP para atenuar la DN.


Assuntos
Extratos Vegetais/administração & dosagem , Nefropatias Diabéticas/tratamento farmacológico , Podócitos/efeitos dos fármacos , Pós , Extratos Vegetais/genética , Ciclo Celular , Western Blotting , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Glucose
7.
Phytomedicine ; 77: 153275, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32659678

RESUMO

BACKGROUND: The tuber of Pinellia ternata has been used for a thousand years in China. P. ternata possessed the activities of anti-emetic, sedative-hypnotic, anti-cancer, anti-asthmatic, anti-tussive, and anti-inflammatory. It is the representative of expectorant medicines in Traditional Chinese Medicine (TCM). Phlegm is the pathological product and a new pathogenic factor of the metabolite, which is analogous to the damage of oxidative stress. PURPOSE: The objectives of the study were to investigate the protective activity and mechanism of ethanol extract of P. ternata tubers (PTE) and its main constituents on oxidative stress-induced cell senescence. METHODS: H2O2 and AAPH were used to establish cellular senescence models. The anti-aging effects of PTE and its components were evaluated by SA-ß-gal staining, flow cytometry, scanning electron microscope (SEM), and multiple microplate reader, the molecular mechanisms of them were investigated by qRT-PCR and Western Blot. RESULTS: We found PTE exhibited the apparent effect on cell senescence, evidenced by inhibiting senescence ß-Galactosidase (SA-ß-gal) expression, lipofuscin accumulation, cell cycle arrest at the G2/M phase, oxidative damage and apoptosis, and increasing telomerase activity. Their mechanisms were related to increase expressions of SIRT1, forkhead box 3a (Foxo3a), Bcl-2, active regulator of SIRT1, RPS19BP1 (AROS), and Hu antigen R (HuR), but decrease Bax, p53 and deleted in breast cancer 1 (DBC1) levels. Furthermore, adenosine, and succinic acid, as the critical substances in PTE, could also inhibit SA-ß-gal expression and cell cycle arrest, down-regulate the expression of Bax, and up-regulate Bcl-2, SirT1, and Foxo3a. CONCLUSIONS: We have demonstrated that PTE slows down oxidative stress-induced cell senescence, and adenosine and succinic acid are the key active components.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Pinellia/química , Extratos Vegetais/farmacologia , Animais , Senescência Celular/efeitos dos fármacos , Chlorocebus aethiops , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Etanol/química , Humanos , Peróxido de Hidrogênio/farmacologia , Lipofuscina/metabolismo , Células PC12 , Extratos Vegetais/química , Tubérculos/química , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Proteínas/genética , Proteínas/metabolismo , Ratos , Telomerase/metabolismo , Células Vero , beta-Galactosidase/metabolismo
8.
New Phytol ; 228(1): 163-178, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32464682

RESUMO

Transport and homeostasis of transition metals in chloroplasts, which are accurately regulated to ensure supply and to prevent toxicity induced by these metals, are thus crucial for chloroplast function and photosynthetic performance. However, the mechanisms that maintain the balance of transition metals in chloroplasts remain largely unknown. We have characterized an albino-revertible green 1 (arg1) rice mutant. ARG1 encodes an evolutionarily conserved protein belonging to the ATP-binding cassette (ABC) transporter family. Protoplast transfection and immunogold-labelling assays showed that ARG1 is localized in the envelopes and thylakoid membranes of chloroplasts. Measurements of metal contents, metal transport, physiological and transcriptome changes revealed that ARG1 modulates cobalt (Co) and nickel (Ni) transport and homeostasis in chloroplasts to prevent excessive Co and Ni from competing with essential metal cofactors in chlorophyll and metal-binding proteins acting in photosynthesis. Natural allelic variation in ARG1 between indica and temperate japonica subspecies of rice is coupled with their different capabilities for Co transport and Co content within chloroplasts. This variation underpins the different photosynthetic capabilities in these subspecies. Our findings link the function of the ARG1 transporter to photosynthesis, and potentially facilitate breeding of rice cultivars with improved Co homeostasis and consequently improved photosynthetic performance.


Assuntos
Oryza , Transportadores de Cassetes de Ligação de ATP/metabolismo , Clorofila/metabolismo , Cloroplastos/metabolismo , Cobalto/metabolismo , Homeostase , Níquel/metabolismo , Níquel/toxicidade , Oryza/genética , Fotossíntese , Melhoramento Vegetal
9.
Vaccines (Basel) ; 8(1)2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31935935

RESUMO

Toxoplasma gondii is a protozoan parasite, occurring worldwide, endangers human health and causes enormous economic losses to the Ministry of Agriculture. A safe and effective vaccination is needed to handle these problems. In addition, ideal vaccine production is a challenge in the future. In this study, we knocked out the adenylosuccinate lyase (ADSL) gene and found that the gene reduces the growth rate of T. gondii tachyzoites in vitro under standard growth conditions by plaque or replication experiments. Furthermore, mice that were immunized with tachyzoites of the ME49ΔADSL strain induced 100% protection efficacy against challenge with the type 1 strain RH, type 2 strain ME49 and type 3 strain VEG. All mice that were immunized with ME49ΔADSL had a survival rate of 100% when they were reinfected with wild-type strains, either 30 days or 70 days after immunization, and immunization was also protective against homologous infection with 50 T. gondii ME49 tissue cysts. In addition, the level of Toxoplasma-specific IgG was significantly elevated at 30 and 70 days after immunization. ME49ΔADSL induced high levels of Th1 cytokines (interferon gamma (IFN-γ), interleukin (IL)-12) at 4 weeks after immunization and spleen cell cultures from mice vaccinated for 150 days were able to produce robust INF-γ and IL-12 levels in the supernatant. The results of the present study showed that ΔADSL vaccination induced a T. gondii-specific cellular immune response against further infections. These results suggest that the ADSL-deficient vaccine can induce anti-Toxoplasma gondii humoral and cellular immune responses and has 100% immune protection against post-challenge by the type 1 strain RH, type 2 strain ME49 and type 3 strain VEG. It will be used as an excellent candidate for live vaccines and may contribute in a positive meaning to control human toxoplasmosis.

10.
Acta Crystallogr C Struct Chem ; 75(Pt 7): 960-968, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271385

RESUMO

Coordination polymers (CPs) have been widely studied because of their diverse and adjustable topologies and wide-ranging applications in luminescence, chemical sensors, magnetism, photocatalysis, gas adsorption and separation. In the present work, two coordination polymers, namely poly[(µ5-benzene-1,3,5-tricarboxylato-κ6O1:O1':O3:O3:O5,O5'){µ3-1,3-bis[(1,2,4-triazol-4-yl)methyl]benzene-κ3N:N':N''}di-µ3-hydroxido-dicobalt(II)], [Co2(C9H3O6)(OH)(C12H12N6)]n or [Co2(btc)(OH)(mtrb)]n, (1), and poly[[diaquabis(µ3-benzene-1,3,5-tricarboxylato-κ3O1:O3:O5)bis{µ3-1,3-bis[(1,2,4-triazol-4-yl)methyl]benzene-κ3N:N':N''}tetra-µ3-hydroxido-tetracopper(II)] monohydrate], {[Cu4(C9H3O6)2(OH)2(C12H12N6)2(H2O)2]·H2O}n or {[Cu4(btc)2(OH)2(mtrb)2(H2O)2]·H2O}n, (2), were synthesized by the hydrothermal method using 1,3-bis[(1,2,4-triazol-4-yl)methyl]benzene (mtrb) and benzene-1,3,5-tricarboxylate (btc3-). CP (1) exhibits a (3,8)-coordinated three-dimensional (3D) network of the 3,8T38 topological type, with a point symbol of {4,5,6}2{42·56·616·72·82}, based on the tetranuclear hydroxide cobalt(II) cluster [Co4(µ3-OH)2]. CP (2) shows a (3,8)-coordinated tfz-d topology, with a point symbol of {43}2{46·618·84}, based on the tetranuclear hydroxide copper(II) cluster [Cu4(µ3-OH)2]. The different (3,8)-coordinated 3D networks based on tetranuclear hydroxide-metal clusters of (1) and (2) are controlled by the different central metal ions [CoII for (1) and CuII for (2)]. The thermal stabilities and solid-state optical diffuse-reflection spectra were measured. The energy band gaps (Eg) obtained for (1) and (2) were 2.72 and 2.29 eV, respectively. CPs (1) and (2) exhibit good photocatalytic degradation of the organic dyes methylene blue (MB) and rhodamine B (RhB) under visible-light irradiation.

11.
World Neurosurg ; 123: 383-389, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30528527

RESUMO

BACKGROUND: Extraaxial lymphoma involving the trigeminal nerve, an uncommon condition that presents as a trigeminal schwannoma, resulted in misdiagnosis and a flawed surgical strategy. We report 2 cases: a primary lymphoma of the Meckel cave and a metastasis lymphoma in the prepontine cistern arising from the supraclavicular lymph node. CASE DESCRIPTION: The first patient presented with a 3-month history of persistent, sharp facial pain across the area innervated by the V2 nerve. She was misdiagnosed with primary trigeminal neuralgia and underwent microvascular decompression. Intraoperatively, the trigeminal nerve was swollen to a large extent and surrounded by red granuloma-like tissue. The second case was a 75-year-old woman; she had a history of a malignant lymphoma of the supraclavicular lymph node and presented with right facial pain. Magnetic resonance imaging revealed that the cisternal portion of the right trigeminal nerve was swollen. A specimen was taken from the 2 patients, and histopathologic examinations revealed a diffuse large B cell lymphoma. CONCLUSIONS: The diagnosis of a malignant lymphoma should be considered for lesions in the trigeminal region. Extracting a specimen for biopsy is the most suitable surgical strategy. Our report indicates that postoperative adjuvant chemotherapy for malignant lymphomas is essential.


Assuntos
Linfoma Difuso de Grandes Células B/complicações , Neuralgia do Trigêmeo/etiologia , Idoso , Antígenos CD20/metabolismo , Feminino , Humanos , Antígenos Comuns de Leucócito/metabolismo , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/cirurgia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Neuralgia do Trigêmeo/diagnóstico por imagem
12.
Front Microbiol ; 9: 2822, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519229

RESUMO

Toxoplasma gondii (T. gondii) is a zoonotic parasite that severely harms the health of the host. The cysts of T. gondii can reactivate from bradyzoites to tachyzoites, if the individual develops low or defective immunity, causing lethal toxoplasmosis. The host resists T. gondii infection by mediating Th1-type cellular immunity to generate pro-inflammatory cytokines. Tumor necrosis factor (TNF) is an important pro-inflammatory cytokine, which can induce lysosomal fusion of parasitophorous vacuole (PV) to kill parasites. Etanercept is a soluble TNF receptor fusion protein, which is widely used clinically to cure autoimmune diseases. The effects and specific molecular mechanisms of etanercept treatment on patients co-infected with autoimmune diseases and chronic toxoplasmosis are rarely reported. In our study, a mouse model of chronic infection with T. gondii and murine macrophages RAW264.7 cells infected with T. gondii were employed to investigate the impact of etanercept on the status of chronic infection. The cytokines levels and a series of phenotypic experiments in vivo and in vitro were measured. In the present study, the expression levels of TNF, IL-1ß, and IL-6 were decreased and the brain cysts number was increased in mice chronically infected with T. gondii after being treated with etanercept. In vivo experiments confirmed that etanercept caused a decrease in the immune levels of the mice and activated the brain cysts, which would lead to conversion from chronic infection to acute infection, causing severe clinical and pathological symptoms. Murine macrophages RAW264.7 cells were pretreated with etanercept, and then infected with T. gondii. In vitro experiments, the expression levels of cytokines were decreased, indicating that etanercept could also reduce the cells' immunity and promote the transformation of bradyzoites to tachyzoites, but did not affect the intracellular replication of tachyzoites. In summary, etanercept treatment could activate the conversion of bradyzoites to tachyzoites through reducing host immunity in vivo and in vitro. The results obtained from this study suggest that the use of etanercept in patients co-infected with autoimmune diseases and chronic toxoplasmosis may lead to the risk of activation of chronic infection, resulting in severe acute toxoplasmosis.

13.
Materials (Basel) ; 12(1)2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30577554

RESUMO

Microchannel tube (MCT) is widely employed in industry due to its excellent efficiency in heat transfer. An MCT is commonly produced through extrusion within a porthole die, where severe plastic deformation is inevitably involved. Moreover, the plastic deformation, which dramatically affects the final property of the MCT, varies significantly from location to location. In order to understand the development of the microstructure and its effect on the final property of the MCT, the viscoplastic self-consistent (VPSC) model, together with the finite element analysis and the flow line model, is employed in the current study. The flow line model is used to reproduce the local velocity gradient within the complex porthole die, while VPSC model is employed to predict the evolution of the microstructure accordingly. In addition, electron backscatter diffraction (EBSD) measurement and mechanical tests are used to characterize the evolution of the microstructure and the property of the MCT. The simulation results agree well with the corresponding experimental ones. The influence of the material's flow line on the evolution of the orientation and morphology of the grains, and the property of the produced MCT are discussed in detail.

14.
Expert Opin Drug Metab Toxicol ; 13(3): 323-330, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27766890

RESUMO

INTRODUCTION: Apigenin, a natural flavone, is widely distributed in plants such as celery, parsley and chamomile. It is present principally as glycosylated in nature. Higher intake of apigenin could reduce the risk of chronic diseases. It has gained particular interest in recent years as a beneficial, health-promoting agent with low intrinsic toxicity. Areas covered: This review summarizes and the absorption, distribution, metabolism and excretion (ADME) properties of apigenin, and drug-drug interaction of apigenin. Expert opinion: Since apigenin is a bioactive plant flavone and is widely distributed in common food, its consumption through the diet is recommended. Apigenin-enriched drugs are better for some chronic diseases, but may affect animal and human health if present in the daily diet. Dietary or therapeutic apigenin has value as a good cellular regulator in cancer, especially cancers of the gastrointestinal tract. Due to apigenin's limitations on absorption and bioavailability, novel carriers would need to be developed to enhance the oral bioavailability of apigenin. Further research about its ADME properties and drug-drug interactions are needed before apigenin can be brought to clinical trials.


Assuntos
Apigenina/farmacocinética , Interações Medicamentosas , Extratos Vegetais/farmacocinética , Animais , Disponibilidade Biológica , Interações Ervas-Drogas , Humanos
15.
Sci Rep ; 6: 28044, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27363496

RESUMO

Notch ligands and receptors are frequently deregulated in several human malignancies including gastric cancer. The activation of Notch signaling has been reported to contribute to gastric carcinogenesis and progression. However, the prognostic roles of individual Notch receptors in gastric cancer patients remain elusive. In the current study, we accessed the prognostic roles of four Notch receptors, Notch 1-4, in gastric cancer patients through "The Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information include a total of 876 gastric cancer patients. All four Notch receptors' high mRNA expression was found to be correlated to worsen overall survival (OS) for all gastric cancer patients followed for 20 years. We further accessed the prognostic roles of individual Notch receptors in different clinicopathological features using Lauren classification, pathological grades, clinical grades, HER2 status and different choices of treatments of gastric cancer patients. These results indicate that there are critical prognostic values of the four Notch receptors in gastric cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of gastric cancer and to develop tools to more accurately predict their prognosis.


Assuntos
Proteínas de Neoplasias/biossíntese , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Receptor Notch1/biossíntese , Receptor Notch4/biossíntese , Neoplasias Gástricas , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida
16.
J Biomater Appl ; 31(2): 261-72, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27288463

RESUMO

The clinical use of daunomycin is restricted by dose-dependent toxicity and low specificity against cancer cells. In the present study, modified superparamagnetic iron oxide nanoparticles were employed to load daunomycin and the drug-loaded nanospheres exhibited satisfactory size and smart pH-responsive release. The cellular uptake efficiency, targeted cell accumulation, and cell cytotoxicity experimental results proved that the superparamagnetic iron oxide nanoparticle-loading process brings high drug targeting without decreasing the cytotoxicity of daunomycin. Moreover, a new concern for the evaluation of nanophase drug delivery's effects was considered, with monitoring the interactions between human serum albumin and the drug-loaded nanospheres. Results from the multispectroscopic techniques and molecular modeling calculation elucidate that the drug delivery has detectable deleterious effects on the frame conformation of protein, which may affect its physiological function.


Assuntos
Daunorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Compostos Férricos/química , Nanopartículas de Magnetita/química , Sobrevivência Celular , Doxorrubicina/química , Liberação Controlada de Fármacos , Células HeLa , Humanos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Simulação de Acoplamento Molecular , Nanosferas/química , Albumina Sérica/química
17.
Bioorg Chem ; 60: 110-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25989424

RESUMO

Intensive reports allowed the conclusion that molecules with extended aromatic surfaces always do good jobs in the DNA interactions. Inspired by the previous successful researches, herein, we designed a series of cationic porphyrins with expanded planar substituents, and evaluated their binding behaviors to G-quadruplex DNA using the combination of surface-enhanced raman, circular dichroism, absorption spectroscopy and fluorescence resonance energy transfer melting assays. Asymmetrical tetracationic porphyrin with one phenyl-4-N-methyl-4-pyridyl group and three N-methyl-4-pyridyl groups exhibit the best G4-DNA binding affinities among all the designed compounds, suggesting that the bulk of the substituents should be matched to the width of the grooves they putatively lie in. Theoretical calculations applying the density functional theory have been carried out and explain the binding properties of these porphyrins reasonably. Meanwhile, these porphyrins were proved to be potential photochemotherapeutic agents since they have photocytotoxic activities against both myeloma cell (Ag8.653) and gliomas cell (U251) lines.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , DNA/metabolismo , Quadruplex G/efeitos dos fármacos , Porfirinas/química , Porfirinas/farmacologia , Antineoplásicos/síntese química , Cátions/síntese química , Cátions/química , Cátions/farmacologia , Linhagem Celular Tumoral , Dicroísmo Circular , DNA/química , Transferência Ressonante de Energia de Fluorescência , Humanos , Luz , Modelos Moleculares , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/síntese química , Termodinâmica , Raios Ultravioleta
18.
Plant J ; 60(6): 1055-69, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19765235

RESUMO

Cellulose synthase-like (CSL) proteins of glycosyltransferase family 2 (GT2) are believed to be involved in the biosynthesis of cell-wall polymers. The CSL D sub-family (CSLD) is common to all plants, but the functions of CSLDs remain to be elucidated. We report here an in-depth characterization of a narrow leaf and dwarf1 (nd1) rice mutant that shows significant reduction in plant growth due to retarded cell division. Map-based cloning revealed that ND1 encodes OsCSLD4, one of five members of the CSLD sub-family in rice. OsCSLD4 is mainly expressed in tissues undergoing rapid growth. Expression of OsCSLD4 fluorescently tagged at the C- or N-terminus in rice protoplast cells or Nicotiana benthamiana leaves showed that the protein is located in the endoplasmic reticulum or Golgi vesicles. Golgi localization was verified using phenotype-rescued transgenic plants expressing OsCSLD4-GUS under the control of its own promoter. Two phenotype-altered tissues, culms and root tips, were used to investigate the specific wall defects. Immunological studies and monosaccharide compositional and glycosyl linkage analyses explored several wall compositional effects caused by disruption of OsCSLD4, including alterations in the structure of arabinoxylan and the content of cellulose and homogalacturonan, which are distinct in the monocot grass species Oryza sativa (rice). The inconsistent alterations in the two tissues and the observable structural defects in primary walls indicate that OsCSLD4 plays important roles in cell-wall formation and plant growth.


Assuntos
Parede Celular/metabolismo , Glucosiltransferases/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/genética , Proteínas de Plantas/metabolismo , Sequência de Aminoácidos , Clonagem Molecular , DNA de Plantas/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Glucosiltransferases/genética , Complexo de Golgi/metabolismo , Dados de Sequência Molecular , Oryza/enzimologia , Pectinas/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Alinhamento de Sequência , Análise de Sequência de DNA , Xilanos/metabolismo
19.
Zhonghua Er Ke Za Zhi ; 44(5): 369-73, 2006 May.
Artigo em Chinês | MEDLINE | ID: mdl-16780716

RESUMO

OBJECTIVE: Vasoactive intestinal peptide (VIP) is a neuro-peptide that can modulate immunity in several aspects. Previous reports showed that VIP attenuates the deleterious consequences of severe infection and septic shock by regulating production of inflammatory cytokines in immune activated cells. Intestine is one of the major organ of immune system and it may trigger multiple organ dysfunction syndrome in sepsis. The present study was planned to study the change of serum TNF-alpha, IL-1beta, IL-10 level and histopathological alteration of intestinal tract, and protective effects of VIP on endotoxic shock in rat. METHODS: Twenty eight SD rats were randomly divided into 3 groups, including control group (8 rats), LPS shock group (10 rats), and LPS + VIP group (10 rats). Endotoxic shock model was established by administration of a single dose of 10 mg/kg LPS in LPS shock group, a bolus of 5 nmol VIP intravenous injection following LPS in LPS + VIP group. The rats in the control group were given the same volume of normal saline injection. Blood samples were taken at time points of 1, 2, 4, and 6 hours after intervention from each group for measuring the level of TNF-alpha, IL-1beta and IL-10 by ELISA. Pathological changes of the intestine were observed by light microscope and electron microscope at the animals death or at the end of the experiment. RESULTS: Serum TNF-alpha, IL-1beta and IL-10 levels elevated at each time point in LPS shock group and LPS + VIP group (P < 0.05 or P < 0.01). TNF-alpha concentration reached the peak level 2 h after LPS injection; IL-1beta and IL-10 increased continuously till the end of the experiment. In LPS + VIP group, TNF-alpha and IL-1beta elevated slightly and IL-10 increased significantly as compared with LPS shock group (P < 0.01). Leukocyte infiltration, ischemia, segmental hemorrhage or necrosis appeared in intestine under light microscope and cell swelling, cytoplasmic vacuoles and organelle damage were observed under electron microscope. However, pathological changes in LPS + VIP group were milder than those in LPS group. CONCLUSIONS: VIP improved endotoxic shock-associated histopathological alteration of intestine, down-regulated pro-inflammatory cytokines production and up-regulated anti-inflammatory cytokines. These effects may suggest a protective mechanism of VIP in septic shock. VIP is a potential immunoregulatory substance in treatment of septic shock.


Assuntos
Intestinos/efeitos dos fármacos , Choque Séptico/tratamento farmacológico , Choque Séptico/imunologia , Peptídeo Intestinal Vasoativo/imunologia , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Interleucina-10/sangue , Interleucina-1beta/sangue , Intestinos/patologia , Intestinos/ultraestrutura , Lipopolissacarídeos/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley , Choque Séptico/sangue , Fator de Necrose Tumoral alfa/sangue , Peptídeo Intestinal Vasoativo/administração & dosagem
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