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1.
Cell Rep ; 42(12): 113477, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-37979167

RESUMO

Targeting lysine-specific histone demethylase 1A (LSD1) can improve tumor immunogenicity of poorly immunogenic tumors, such as non-small cell lung cancer (NSCLC), with elevated T cell infiltration and sensitize tumors to anti-PD-1 therapy. However, the lack of reliable biomarkers limits utilization of LSD1 inhibitors in cancer therapy. Here, we identify an E3 ligase, Trim35, as an effective biomarker for high activity of LSD1 to predict prognosis of LSD1-targeted therapy as well as immunotherapy. Mechanistically, Trim35 represses LSD1 demethylase activity by mediating K63 ubiquitination at lysine site 422 of LSD1. Suppressed LSD1 activity facilitates ERGIC1 transcription, followed by autophagy inhibition and IFNGR1 stabilization to activate IFN-γ signaling, leading to increased MHC class I expression and immune surveillance of NSCLC cells. Furthermore, combinational use of an LSD1 inhibitor and anti-PD-1 therapy can significantly eradicate poorly immunogenic lung cancer with low Trim35. These findings strongly suggest that Trim35 is a promising biomarker for prediction of immunotherapy outcome in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Ubiquitina-Proteína Ligases/metabolismo , Lisina/metabolismo , Ubiquitinação , Histona Desmetilases/metabolismo , Biomarcadores/metabolismo , Linhagem Celular Tumoral
2.
EMBO Rep ; 24(9): e55060, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37477088

RESUMO

Inflammation plays an important role in the initiation and progression of colorectal cancer (CRC) and leads to ß-catenin accumulation in colitis-related CRC. However, the mechanism remains largely unknown. Here, pancreatic progenitor cell differentiation and proliferation factor (PPDPF) is found to be upregulated in CRC and significantly correlated with tumor-node-metastasis (TNM) stages and survival time. Knockout of PPDPF in the intestinal epithelium shortens crypts, decreases the number of stem cells, and inhibits the growth of organoids and the occurrence of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC. Mechanistically, PPDPF is found to interact with Casein kinase 1α (CK1α), thereby disrupting its binding to Axin, disassociating the ß-catenin destruction complex, decreasing the phosphorylation of ß-catenin, and activating the Wnt/ß-catenin pathway. Furthermore, interleukin 6 (IL6)/Janus kinase 2 (JAK2)-mediated inflammatory signals lead to phosphorylation of PPDPF at Tyr16 and Tyr17, stabilizing the protein. In summary, this study demonstrates that PPDPF is a key molecule in CRC carcinogenesis and progression that connects inflammatory signals to the Wnt/ß-catenin signaling pathway, providing a potential novel therapeutic target.


Assuntos
Neoplasias Colorretais , Interleucina-6 , Humanos , Interleucina-6/efeitos adversos , Interleucina-6/metabolismo , Fosforilação , beta Catenina/metabolismo , Via de Sinalização Wnt , Janus Quinase 2/metabolismo , Neoplasias Colorretais/genética , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
3.
ACS Appl Mater Interfaces ; 15(19): 23371-23379, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37155833

RESUMO

Memristive devices, regardless of their potential applications in memory and computing scenarios, still suffer from large cycle-to-cycle and device-to-device variations due to the stochastic growth of conductive filaments (CFs). In this work, we fabricated a crossbar memristor using the 2D TiSe2 material and then oxidized it into TiO2 in the atmosphere at a moderate temperature. Such a mild oxidation approach fails to evaporate all Se into the air, and after further annealing using thermal or electrical stimulations, the remnant Se atoms gather near the interfaces and grow into nanosized crystals with relatively high conductivity. The resulting peninsula-shaped nanocrystals distort the electric field, forcing CFs to grow on them, which could largely confine the location and length of CFs. As a result, this two-terminal TiSe2/TiO2/TiSe2 device exhibits excellent resistive switching performance with a fairly low threshold voltage (Vset < 0.8 V, Vreset > 0.55 V) and high cycle-to-cycle consistency, enabling resistive switching at narrow operating variations, e.g., 500 ± 48 and 845 ± 39 mV. Our work offers a new approach to minimize the cycle-to-cycle stochasticity of the memristive device, paving the way for its applications in data storage and brain-inspired computing.

4.
Environ Sci Pollut Res Int ; 30(5): 13551-13559, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36136195

RESUMO

Rice agriculture is both an important source of the potent greenhouse gas methane (CH4) and a bioaccumulator of cadmium (Cd), which is hazardous to human health. Avoiding flooding during rice production is effective for reducing CH4 emissions, but it increases rice Cd uptake. Although lime application decreases Cd concentration in rice grains, it is not clear whether combining appropriate water management with liming can simultaneously reduce CH4 emissions and Cd uptake in rice paddies. Thus, a pot experiment was performed to investigate the interactive effects of water management (F: continuous flooding, FDF: flooding - midseason drainage - flooding, FDI: flooding - midseason drainage - intermittent irrigation) and lime application on CH4 emissions and rice Cd uptake in an acid paddy soil spiked with Cd. Results showed that neither water management nor liming significantly affected grain yield. Overall, liming reduced CH4 emissions by 42.2%. Compared to F, the FDF and FDI treatments reduced CH4 emissions by 43.5% and 54.2%, respectively. Liming reduced CH4 emissions by 32.6% under F, but with a greater decrease of 48.6% and 52.7% under FDF and FDI, respectively. Overall, liming reduced rice Cd uptake by an average of 47.3%. Compared to FDI, F and FDF significantly reduced Cd uptake by 84.0% and 75.1%, respectively, but there was no significant difference between F and FDF. Liming did not significantly affect Cd uptake under F and FDF, whereas liming reduced Cd uptake by 55.9% under FDI. These results suggest that maintaining flooding following midseason drainage can help in reducing rice Cd uptake, though slightly promoting CH4 emissions. Therefore, we recommend FDF combined with liming to mitigate CH4 emissions without increasing rice Cd uptake in acid paddy soils.


Assuntos
Oryza , Solo , Humanos , Água/análise , Cádmio/análise , Agricultura/métodos , Metano , Abastecimento de Água , Óxido Nitroso/análise
5.
Plant Physiol Biochem ; 194: 70-84, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36379179

RESUMO

Carbon reserves in cotton roots can be remobilized to support reproductive growth, thus potentially affecting cotton yield. However, the regulation of carbon remobilization in cotton roots and its relationship with cotton yield are still poorly understood. Plant population density (PPD) and mepiquat chloride (MC) have been hypothesized to affect the dynamics of nonstructural carbohydrate content and the resulting carbon remobilization in cotton roots through the regulation of carbohydrate metabolism enzyme activities. A mid-maturation cotton line 4003-6 was field-grown in 2019 and 2020. Three different levels of PPD (D1: 2.25 plants m-2, D2: 4.5 plants m-2, and D3: 6.75 plants m-2) and two levels of MC dosage (M0: 0 g hm-2, M1: 82.5 g hm-2) were combined to create six populations differing in terms of the source-sink relationship. The changes in the hexose, sucrose, and starch contents and the key carbon metabolic enzyme activities in cotton roots were examined during peak squaring (PS) to late boll opening (LB). The combination of the PPD of 6.75 plants m-2 and MC application (M1D3) exhibited the greatest cotton yield and reproductive biomass-to-leaf area ratio from peak flowering (PF) onwards. M1D3 presented the greatest total nonstructural carbohydrate (TNC) remobilization amount of 2.96 and 3.80 g m-2, the highest efficiency of 39.11% and 48.39%, and the largest gross contribution to seed cotton yield of 0.66% and 0.79% in 2019 and 2020, respectively. The three parameters were positively correlated with the seed cotton yield except for the remobilization rate in 2019. Unlike the other treatments, the greater carbohydrate content per unit ground area in M1D3 prior to the PF stage was attributed to the higher sucrose phosphate synthase (SPS) and ADP-glucose pyrophosphorylase (AGPase) activities during the PS to first flowering (FF) stages. Conversely, the greater α-amylase and ß-amylase activities in M1D3 at the PF stage accounted for the lower starch content at the EB stage, and the smaller vacuolar invertase (VIN) and cell wall invertase (CWIN) activities at the EB stage could be responsible for the lower hexose concentration at that time. The TNC remobilization amount had a positive association with the AGPase and SPS activities at the FF stage and with ß-amylase activity at the PF stage in cotton tap roots in 2019 and 2020. This study provides a cotton yield-improving alternative through the promotion of carbon remobilization in roots using certain agronomic practices.


Assuntos
Carbono , beta-Amilase , Carbono/metabolismo , beta-Frutofuranosidase/metabolismo , Densidade Demográfica , beta-Amilase/metabolismo , Raízes de Plantas/metabolismo , Amido/metabolismo , Carboidratos , Gossypium/metabolismo
6.
Cancers (Basel) ; 14(22)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36428781

RESUMO

Girdin, an Akt substrate, has been reported to promote tumorigenesis in various tumors. However, the role of Girdin in a spontaneous tumor model has not yet been explored. Here, we studied the role of Girdin in lung adenocarcinoma (LUAD) using the autochthonous mouse model and found that Girdin led to LUAD progression and chemoresistance by enhancing the Warburg effect. Mechanistically, Girdin interacted with pyruvate kinase M2 (PKM2), which played a vital role in aerobic glycolysis. Furthermore, Girdin impaired Platelet Derived Growth Factor Receptor Beta (PDGFRß) degradation, which in turn, promoted PKM2 tyrosine residue 105 (Y105) phosphorylation and inhibited PKM2 activity, subsequently promoting aerobic glycolysis in cancer cells. Taken together, our study demonstrates that Girdin is a crucial regulator of tumor growth and may be a potential therapeutic target for overcoming the resistance of LUAD cells to chemotherapy.

7.
Biochem Biophys Res Commun ; 630: 175-182, 2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-36155064

RESUMO

Lung adenocarcinoma (LUAD) is the most common type of lung cancers, which remains the leading cause of cancer-related death worldwide. Drebrin can promote cell migration and invasion with poor prognosis, but its roes in LUAD tumor progression remains unknown. We showed that the expression of Drebrin was upregulated in clinical LUAD samples. A Kaplan-Meier survival analysis showed that a high expression of Drebrin predicated poor prognosis in LUAD. In vitro, Drebrin promoted anchorage-independent growth and migration of LUAD cells. Drebrin interacted with dynamin through CT domain, and served as an adaptor to promote LUAD cell migration through inducing integrin ß1 endocytosis. Thus, this study demonstrated the critical role of Drebrin in LUAD and associated mechanism.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Neuropeptídeos , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Endocitose , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina beta1/genética , Integrina beta1/metabolismo , Neoplasias Pulmonares/patologia , Neuropeptídeos/genética
8.
Plant Physiol Biochem ; 178: 125-136, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35298944

RESUMO

Carbohydrates remobilization in non-leaf organs has a potential association with the formation of cotton yield. However, our understanding of the physiological and molecular mechanisms regulating carbon remobilization during flowering is still limited. The objectives of the study were to: i) evaluate the potential of carbohydrate remobilization in stems and roots to yield formation; ii) unravel the carbon metabolism and transport associated gene expression patterns regulating carbon remobilization. Two cotton lines 4003-6 and 4003-10 were employed to examine leaf photosynthesis, reproductive biomass accumulation, and carbon dynamics in stems and roots during reproductive growth. The results showed that decreasing leaf photosynthetic capacity combined with rapidly increasing reproductive biomass and leaf area index is accompanied by the initiation of carbohydrate remobilization during first flowering to peak flowering. The proportion of sucrose to total nonstructural carbohydrate was also decreased at that period. The upper and lower of stem recorded higher soluble sugars and starch concentrations, respectively compared to the two others. The gross contribution rate of carbon remobilization to seed cotton yield ranged from 2.83% to 7.12%. Key genes and sugar transporters related to starch and sucrose metabolism in the lower stem exhibited significant up- or down-regulated expressions indicating their important roles in carbon reserves remobilization. Three pivotal sugar transporters SWEET1, TMT2, and ERLD5 presented higher transcript levels at peak flowering suggesting more active sugar movement occurring at that stage. The present study provides potential target genes for engineering carbohydrate metabolism and transport to improve the remobilization efficiency of nonstructural carbohydrates.


Assuntos
Carbono , Raízes de Plantas , Metabolismo dos Carboidratos/genética , Carboidratos , Carbono/metabolismo , Expressão Gênica , Raízes de Plantas/genética , Raízes de Plantas/metabolismo
9.
Sci Rep ; 12(1): 1704, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105892

RESUMO

Red soil is characterized by poor physico-chemical properties and low nutrient availability. The present study aimed to examine rich husk ash (RHA) incorporation into red soil at various rates effects on its properties and the growth of cotton seedlings under a plug-seeding in tray experiment. Bulk density was decreased, and water holding capacity and total porosity were increased in red soil with increasing application rate of RHA. The addition of RHA counteracts the acidity of red soil and improves the nutrient availability to plants. The RHA incorporated soils favored the growth of cotton seedlings with improved shoot morphological traits and root architectures. The application rate at a volume ratio of 1:1 of RHA to red soil was found to be optimal for growing cotton seedlings in the present study. The mixture of RHA and red soil at a 1:1 volume ratio plus 2 g L-1 super absorbent polymers exhibited a high nursing seedling efficiency comparable to a commercial growing media under the condition of foliar application of mepiquat chloride at the one-true-leaf stage. RHA can be a promising substitute for peat as growing media for nursing cotton seedlings.

10.
Cancer Sci ; 113(2): 565-575, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34807493

RESUMO

Colitis-associated colorectal cancer (CAC) arises due to prolonged inflammation and has distinct molecular events compared with sporadic colorectal cancer (CRC). Although inflammatory NF-κB signaling was activated by pro-inflammatory cytokines (such as TNFα) in early stages of CAC, Wnt/ß-catenin signaling later appears to function as a key regulator of CAC progression. However, the exact mechanism responsible for the cross-regulation between these 2 pathways remains unclear. Here, we found reciprocal inhibition between NF-κB and Wnt/ß-catenin signaling in CAC samples, and the Dvl2, an adaptor protein of Wnt/ß-catenin signaling, is responsible for NF-κB inhibition. Mechanistically, Dvl2 interacts with the C-terminus of tumor necrosis factor receptor 1 (TNFRI) and mediates TNFRI endocytosis, leading to NF-κB signal inhibition. In addition, increased infiltration of the pro-inflammatory cytokine interleukin-13 (IL-13) is responsible for upregulating Dvl2 expression through STAT6. Targeting STAT6 effectively decreases Dvl2 levels and restrains colony formation of cancer cells. These findings demonstrate a unique role for Dvl2 in TNFRI endocytosis, which facilitates the coordination of NF-κB and Wnt to promote CAC progression.


Assuntos
Neoplasias Associadas a Colite/metabolismo , Proteínas Desgrenhadas/metabolismo , NF-kappa B/metabolismo , Proteínas Wnt/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Associadas a Colite/genética , Neoplasias Associadas a Colite/patologia , Citocinas/metabolismo , Progressão da Doença , Proteínas Desgrenhadas/genética , Endocitose , Regulação Neoplásica da Expressão Gênica , Humanos , Inflamação , Camundongos , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
11.
Signal Transduct Target Ther ; 6(1): 408, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836940

RESUMO

Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma, respectively. However, clinical analyses demonstrate that EBV or HPV is associated with improved response of patients, although underlying mechanism remains unclear. Here, we reported that the oncoproteins of DNA viruses, such as LMP1 of EBV and E7 of HPV, inhibit PERK activity in cancer cells via the interaction of the viral oncoproteins with PERK through a conserved motif. Inhibition of PERK led to increased level of reactive oxygen species (ROS) that promoted tumor and enhanced the efficacy of chemotherapy in vivo. Consistently, disruption of viral oncoprotein-PERK interactions attenuated tumor growth and chemotherapy in both cancer cells and tumor-bearing mouse models. Our findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK might be an attractive strategy for the treatment of NPC and cervical carcinoma.


Assuntos
Antineoplásicos/farmacologia , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4/metabolismo , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/metabolismo , Infecções por Papillomavirus/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Proteínas da Matriz Viral/metabolismo , Animais , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Feminino , Células HeLa , Herpesvirus Humano 4/genética , Humanos , Camundongos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Proteínas da Matriz Viral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Immunol Res ; 2021: 9995869, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124276

RESUMO

The majority of diffuse large B-cell lymphoma (DLBCL) patients develop relapsed or refractory disease after standard ruxolitinib, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, which is partly related to a dysregulated tumor immune microenvironment. However, how the infiltration of immune cells is appropriately regulated is poorly understood. Herein, we show that the E3 ubiquitin ligase Trim35 is expressed at low levels in human DLBCL tissues. We also show that overexpression of Trim35 suppresses DLBCL cell proliferation and correlates with inferior survival in DLBCL patients. Our mechanistic study shows that Trim35 functions as an E3 ligase to mediate the ubiquitination and degradation of CLOCK, a key regulator of circadian rhythmicity. High expression of Trim35 correlates with NK cell infiltration in DLBCL, partly due to the degradation of CLOCK. Consistently, patients with high expression of CLOCK show poor overall survival. Overall, these findings suggest that Trim35 suppresses the progression of DLBCL by modulating the tumor immune microenvironment, indicating that it may be a promising diagnostic and prognostic biomarker in DLBCL.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas CLOCK/metabolismo , Células Matadoras Naturais/imunologia , Linfoma Difuso de Grandes Células B/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Reguladoras de Apoptose/genética , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular/genética , Relógios Circadianos/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Proteólise , Análise de Sobrevida , Microambiente Tumoral
13.
Mol Breed ; 41(5): 34, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-37309326

RESUMO

Nulliplex branch is a key architectural trait in sea-island cotton (Gossypium barbadense L.), but its genetic basis is not well understood. Here we investigated the genetic basis of the nulliplex-branch trait in cotton by combining newly created bulked segregant analysis (BSA)-seq data, published RNA-seq data, and published whole-genome resequencing (WGR) data. We delimited the nulliplex-branch locus (qD07-NB) to D07, region 14.8-17.1 Mb, using various BSA methods and markers. We integrated our BSA data with WGR data of sea-island cotton varieties and detected a missense single-nucleotide polymorphism in the candidate gene (Gbar_D07G011870) of qD07-NB. This gene was under positive selection during sea-island cotton breeding in the Xinjiang Uygur Autonomous Region, China. Notably, the nulliplex-branch varieties possessed a better fiber quality than the long-branch varieties, and a set of high-quality molecular markers was identified for molecular breeding of the nulliplex-branch trait in cotton. We combined BSA-seq and RNA-seq data to compare gene expression profiles between two elite sea-island cotton varieties during three developmental stages. We identified eleven relevant candidate genes, five downregulated and six upregulated, in the qD07-NB locus. This research will expand our understanding of the genetic basis of the nulliplex-branch trait and provide guidance for architecture-focused breeding in cotton. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01229-w.

14.
Plant Biotechnol J ; 19(3): 462-476, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32902115

RESUMO

Abiotic stresses such as extreme temperatures, water-deficit and salinity negatively affect plant growth and development, and cause significant yield losses. It was previously shown that co-overexpression of the Arabidopsis vacuolar pyrophosphatase gene AVP1 and the rice SUMO E3 ligase gene OsSIZ1 in Arabidopsis significantly increased tolerance to multiple abiotic stresses and led to increased seed yield for plants grown under single or multiple abiotic stress conditions. It was hypothesized that there might be synergistic effects between AVP1 overexpression and OsSIZ1 overexpression, which could lead to substantially increased yields if these two genes are co-overexpressed in real crops. To test this hypothesis, AVP1 and OsSIZ1 were co-overexpressed in cotton, and the impact of OsSIZ1/AVP1 co-overexpression on cotton's performance under normal growth and multiple stress conditions were analysed. It was found that OsSIZ1/AVP1 co-overexpressing plants performed significantly better than AVP1-overexpressing, OsSIZ1-overexpressing and wild-type cotton plants under single, as well as under multiple stress conditions in laboratory and field conditions. Two field studies showed that OsSIZ1/AVP1 co-overexpressing plants produced 133% and 81% more fibre than wild-type cotton in the dryland conditions of West Texas. This research illustrates that co-overexpression of AVP1 and OsSIZ1 is a viable strategy for engineering abiotic stress-tolerant crops and could substantially improve crop yields in low input or marginal environments, providing a solution for food security for countries in arid and semiarid regions of the world.


Assuntos
Proteínas de Arabidopsis , Secas , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Gossypium/genética , Gossypium/metabolismo , Temperatura Alta , Pirofosfatase Inorgânica/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Salinidade , Estresse Fisiológico
15.
Mater Sci Eng C Mater Biol Appl ; 117: 111298, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919659

RESUMO

A purely physically crosslinked double network (DN) hydrogel, poly(sulfobetaine-co-acrylic acid)/chitosan-citrate (P(SBMA-co-AAc)/CS-Cit) DN hydrogel, was prepared based on electrostatic interaction and hydrogen bonding between the polymer chains. The hydrogel is highly stretchable, transparent, anti-fatigue, self-adhesive and has good self-healing properties with a self-healing efficiency as high as 95.4%. Furthermore, the resistance of the P(SBMA-co-AAc)/CS-Cit DN hydrogel is sensitive to a wide strain window and the relative resistance shows stable and reliable change during deformation. Herein, the hydrogel was demonstrated as a strain sensor to detect human motions, such as joint bending and swallowing. More excitingly, before ionic crosslinking, the P(SBMA-co-AAc)/CS-Cit composite hydrogel is injectable, thus the P(SBMA-co-AAc)/CS-Cit DN hydrogel sensor can be made into various complex shapes by injecting the P(SBMA-co-AAc)/CS-Cit composite hydrogel into citrate solution, including multilayer structures, exhibiting a great potential for applications as 3D printing strain sensors.


Assuntos
Quitosana , Dispositivos Eletrônicos Vestíveis , Adesivos , Humanos , Hidrogéis , Impressão Tridimensional , Cimentos de Resina
16.
Front Cell Dev Biol ; 8: 490, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32626713

RESUMO

Upon interactions with its specific ligand hepatocyte growth factor (HGF), the c-Met signal is relayed to series of downstream pathways, exerting essential biological roles. Dysregulation of the HGF-c-Met signaling pathway has been implicated in the onset, progression and metastasis of various cancers, making the HGF-c-Met axis a promising therapeutic target. Both c-Met and HGF undergo glycosylation, which appears to be biologically relevant to their function and structural integrity. Different types of glycoconjugates in the local cellular environment can also regulate HGF/c-Met signaling by distinct mechanisms. However, detailed knowledge pertaining to the glycosylation machinery of the HGF-c-Met axis as well as its potential applications in oncology research is yet to be established. This mini review highlights the significance of the HGF-c-Met signaling pathway in physiological and pathological context, and discusses the molecular mechanisms by which affect the glycosylation of the HGF-c-Met axis. Owing to the crucial role played by glycosylation in the regulation of HGF/c-Met activity, better understanding of this less exploited field may contribute to the development of novel therapeutics targeting glycoepitopes.

17.
Cancer Biol Med ; 17(2): 328-342, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32587772

RESUMO

Objectives: Improper activation of Wnt/ß-catenin signaling has been implicated in human diseases. Beyond the well-studied glycogen synthase kinase 3ß (GSK3ß) and casein kinase 1 (CK1), other kinases affecting Wnt/ß-catenin signaling remain to be defined. Methods:To identify the kinases that modulate Wnt/ß-catenin signaling, we applied a kinase small interfering RNA (siRNA) library screen approach. Luciferase assays, immunoblotting, and real-time polymerase chain reaction (PCR) were performed to confirm the regulation of the Wnt/ß-catenin signaling pathway by cyclin-dependent kinase 11 (CDK11) and to investigate the underlying mechanism. Confocal immunofluorescence, coimmunoprecipitation (co-IP), and scratch wound assays were used to demonstrate colocalization, detect protein interactions, and explore the function of CDK11. Results: CDK11 was found to be a significant candidate kinase participating in the negative control of Wnt/ß-catenin signaling. Down-regulation of CDK11 led to the accumulation of Wnt/ß-catenin signaling receptor complexes, in a manner dependent on intact adenomatosis polyposis coli (APC) protein. Further analysis showed that CDK11 modulation of Wnt/ß-catenin signaling engaged the endolysosomal machinery, and CDK11 knockdown enhanced the colocalization of Wnt/ß-catenin signaling receptor complexes with early endosomes and decreased colocalization with lysosomes. Mechanistically, CDK11 was found to function in Wnt/ß-catenin signaling by regulating microtubule stability. Depletion of CDK11 down-regulated acetyl-α-tubulin. Moreover, co-IP assays demonstrated that CDK11 interacts with the α-tubulin deacetylase SIRT2, whereas SIRT2 down-regulation in CDK11-depleted cells reversed the accumulation of Wnt/ß-catenin signaling receptor complexes. CDK11 was found to suppress cell migration through altered Wnt/ß-catenin signaling. Conclusions: CDK11 is a negative modulator of Wnt/ß-catenin signaling that stabilizes microtubules, thus resulting in the dysregulation of receptor complex trafficking from early endosomes to lysosomes.


Assuntos
Quinases Ciclina-Dependentes/metabolismo , Regulação para Baixo , Endossomos/metabolismo , Microtúbulos/metabolismo , Proteína da Polipose Adenomatosa do Colo , Linhagem Celular Tumoral , Quinases Ciclina-Dependentes/genética , Endossomos/genética , Humanos , Luciferases/análise , Luciferases/genética , Microtúbulos/genética , Sirtuína 2/genética , Sirtuína 2/metabolismo , Proteínas Wnt , Via de Sinalização Wnt , beta Catenina
18.
Oncotarget ; 8(32): 52333-52344, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28881733

RESUMO

The Epstein-Barr virus latent membrane protein 1 (LMP1) is an integral membrane protein. LMP1 has been reported to activate the NF-κB and mitogen-activated protein kinase pathways. However, these effects alone are unable to account for the profound oncogenic properties of LMP1. TAZ is one of the nuclear effectors of Hippo-related pathways and highly expressed in many human tumors. Here, we reported that TAZ was frequently expressed in LMP1-positive nasopharyngeal carcinoma. In NPC cell lines, we showed that LMP1 promoted TAZ expression. Gelsolin is an important inhibitor of TAZ activity. Our studies showed that LMP1 interacted with gelsolin, resulting in inhibition of Lats1/2 phosphorylation and improvement of TAZ stability. Furthermore, we revealed that TAZ is important for LMP1-mediated cell proliferation, cancer stem cell-like properties and epithelial-mesenchymal transition. These findings provide new insights into the carcinogenic roles of LMP1 and contribute to further understanding of its oncogenic mechanism.

19.
J Integr Plant Biol ; 57(5): 450-67, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25263268

RESUMO

To introgress the good fiber quality and yield from Gossypium barbadense into a commercial Upland cotton variety, a high-density simple sequence repeat (SSR) genetic linkage map was developed from a BC1 F1 population of Gossypium hirsutum × Gossypium barbadense. The map comprised 2,292 loci and covered 5115.16 centiMorgan (cM) of the cotton AD genome, with an average marker interval of 2.23 cM. Of the marker order for 1,577 common loci on this new map, 90.36% agrees well with the marker order on the D genome sequence genetic map. Compared with five published high-density SSR genetic maps, 53.14% of marker loci were newly discovered in this map. Twenty-six quantitative trait loci (QTLs) for lint percentage (LP) were identified on nine chromosomes. Nine stable or common QTLs could be used for marker-assisted selection. Fifty percent of the QTLs were from G. barbadense and increased LP by 1.07%-2.41%. These results indicated that the map could be used for screening chromosome substitution segments from G. barbadense in the Upland cotton background, identifying QTLs or genes from G. barbadense, and further developing the gene pyramiding effect for improving fiber yield and quality.


Assuntos
Mapeamento Cromossômico , Cruzamentos Genéticos , Ligação Genética , Gossypium/genética , Locos de Características Quantitativas/genética , Têxteis , Alelos , Cromossomos de Plantas/genética , Frequência do Gene/genética , Loci Gênicos , Marcadores Genéticos , Genoma de Planta , Genótipo , Heterozigoto , Repetições de Microssatélites/genética , Polimorfismo Genético , Poliploidia
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