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1.
Immunol Cell Biol ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044372

RESUMO

Therapy-induced senescence can regulate both the innate and adaptive immune systems, thereby affecting therapeutic efficacy. Bleomycin is a major component of combined chemotherapy regimens, utilized for the treatment of multiple tumors, whereas pulmonary toxicity severely restricts its clinical benefits. As a member of the bleomycin family, boningmycin (BON) exhibits potent anticancer activity with minimal pulmonary toxicity, making it a potential alternative to bleomycin. Low concentrations of BON can induce senescence, but the impact of BON-induced senescence on anticancer immunity remains unclear. This study investigates the effects of BON-induced senescence on PD-L1 expression and the underlying mechanisms in human cancer cells. Firstly, the elevation of PD-L1 protein during BON-induced senescence was confirmed by a senescence ß-galactosidase staining assay, detection of the senescence-associated secretory phenotype (SASP), western blot and flow cytometry in human lung cancer NCI-H460 cells and breast cancer MDA-MB-231 cells. Subsequently, it was shown that the increase in PD-L1 protein is mediated by SASP, as evidenced by the use of conditional media, knockdown of cyclic GMP-AMP synthase and inhibition of stimulator of interferon genes. Ultimately, it was demonstrated that SASP-mediated PD-L1 up-regulation is dependent on the activation of the JAK/STAT pathway through the use of specific inhibitors and siRNAs. These findings clarify the impact of BON-induced senescence on PD-L1 expression and may contribute to the optimization of the therapeutic efficacy of bleomycin-related compounds and the clinical transformation of BON.

2.
Pestic Biochem Physiol ; 202: 105969, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879313

RESUMO

Populus pseudo-cathayana × Populus deltoides is a crucial artificial forest tree species in Northeast China. The presence of the fall webworm (Hyphantria cunea) poses a significant threat to these poplar trees, causing substantial economic and ecological damage. This study conducted an insect-feeding experiment with fall webworm on P. pseudo-cathayana × P. deltoides, examining poplar's physiological indicators, transcriptome, and metabolome under different lengths of feeding times. Results revealed significant differences in phenylalanine ammonia-lyase activity, total phenolic content, and flavonoids at different feeding durations. Transcriptomic analysis identified numerous differentially expressed genes, including AP2/ERF, MYB, and WRKY transcription factor families exhibiting the highest expression variations. Differential metabolite analysis highlighted flavonoids and phenolic acid compounds of poplar's leaves as the most abundant in our insect-feeding experiment. Enrichment analysis revealed significant enrichment in the plant hormone signal transduction and flavonoid biosynthetic pathways. The contents of jasmonic acid and jasmonoyl-L-isoleucine increased with prolonged fall webworm feeding. Furthermore, the accumulation of dihydrokaempferol, catechin, kaempferol, and naringenin in the flavonoid biosynthesis pathway varied significantly among different samples, suggesting their crucial role in response to pest infestation. These findings provide novel insights into how poplar responds to fall webworm infestation.


Assuntos
Populus , Populus/genética , Populus/metabolismo , Animais , Flavonoides/metabolismo , Besouros/fisiologia , Besouros/metabolismo , Oxilipinas/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Fenilalanina Amônia-Liase/genética , Ciclopentanos/metabolismo , Folhas de Planta/metabolismo , Transcriptoma , Regulação da Expressão Gênica de Plantas , Mariposas/genética , Mariposas/fisiologia , Reguladores de Crescimento de Plantas/metabolismo
3.
BMC Surg ; 24(1): 174, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824553

RESUMO

BACKGROUND: The purpose of this study was to investigate effect of liver Transplants (LT) with retrograde reperfusion on early postoperative recovery of liver function and its risk factors. METHODS: We conducted a retrospective analysis of clinical data from 136 liver transplantation (LT) patients at the 900th Hospital of the Chinese People's Liberation Army Joint Support Army, covering the period from January 2015 to January 2021. All participants provided informed consent, adhering to medical ethics guidelines. Patients were stratified into two groups based on the liver perfusion technique used: retrograde reperfusion (RTR, n = 108) and initial portal reperfusion (IPR, n = 28). Our study focused on a subset of 23 patients from each group to compare postoperative liver function recovery. The final analysis included 86 RTR and 28 IPR cases after excluding 8 RTR patients who underwent initial hepatic artery reperfusion and 14 who received simultaneous hepatic artery and portal vein reperfusion. Further subdivision within the RTR group identified 19 patients with early hepatic allograft dysfunction (EAD) and 67 without, allowing for an assessment of the influence of preoperative and intraoperative parameters, as well as perfusion methods, on EAD incidence post-LT. RESULTS: Alanine aminotransferase (ALT) was 329 (211 ~ 548) and 176 (98 ~ 282) U/L on the 3rd and 7th day after RTR, respectively, which was significantly lower than 451 (288 ~ 918) and 251 (147 ~ 430) U/L in the IPR group (Z =-1.979, -2.299, P = 0.048, 0.021). Aspartate aminotransferase (AST) on postoperative days 3, 5, and 7 was 252 (193, 522), 105 (79, 163), and 93 (41, 135) U/L in the RTR group, respectively; it was also significantly lower than 328 (251, 724), 179 (129, 306), and 150 (91, 200)U/L in the IPR group (Z=-2.212, -3.221, -2.979; P = 0.027, 0.001, 0.003). Logistic regression analysis showed that MELD score was an independent risk factor for EAD after LT. CONCLUSION: RTR LT is more favorable for patients' early postoperative liver function recovery. For patients undergoing LT for RTR, preoperative MELD score was an independent risk factor for their postoperative development of EAD.


Assuntos
Transplante de Fígado , Recuperação de Função Fisiológica , Reperfusão , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Reperfusão/métodos , Adulto , Testes de Função Hepática , Fígado/irrigação sanguínea , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia
4.
Philos Trans A Math Phys Eng Sci ; 381(2244): 20220033, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36774962

RESUMO

Prestressed stayed columns (PSCs) are structural systems whose compressive load-carrying capacity is enhanced through pre-tensioned cable stays. Much research has demonstrated that PSCs buckle subcritically when their prestressing levels maximize the critical buckling load of the theoretically perfect arrangement. Erosion of the pre-tensioned cables' effectiveness (e.g. through creep or corrosion) can thus lead to sudden collapse. The present goal is to develop a structural health monitoring (SHM) technique for in-service PSCs that returns the current structural utilization factor based on selected probing measurements. Hence, PSCs with different cable erosion and varying compression levels are probed in the pre-buckling range within the numerical setting through a nonlinear finite element (FE) model. In contrast to the previous work, it is found presently that the initial lateral stiffness from probing a PSC provides a suitable health index for in-service structures. A machine learning-based surrogate is trained on simulated data of the loading factor, cable erosion and probing indices; it is then used as a predictive tool to return the current utilization factor for PSCs alongside the level of cable erosion given probing measurements, showing excellent accuracy and thus provides confidence that an SHM technique based on probing is indeed feasible. This article is part of the theme issue 'Probing and dynamics of shock sensitive shells'.

5.
Mediators Inflamm ; 2023: 7992140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152370

RESUMO

Liver hepatocellular carcinoma (LIHC) is a highly lethal malignant tumor originating from the digestive system, which is a serious threat to human health. In recent years, immunotherapy has shown significant therapeutic effects in the treatment of LIHC, but only for a minority of patients. The basement membrane (BM) plays an important role in the occurrence and development of tumors, including LIHC. Therefore, this study is aimed at establishing a risk score model based on basement membrane-related genes (BMRGs) to predict patient prognosis and response to immunotherapy. First, we defined three patterns of BMRG modification (C1, C2, and C3) by consensus clustering of BMRG sets and LIHC transcriptome data obtained from public databases. Survival analysis showed that patients in the C2 group had a better prognosis, and Gene Set Variation Analysis (GSVA) revealed that the statistically significant pathways were mainly enriched in the C2 group. Moreover, we performed Weighted Correlation Network Analysis (WGCNA) on the above three subgroups and obtained 179 intersecting genes. We further applied function enrichment analyses, and the results demonstrated that they were mainly enriched in metabolism-related pathways. Furthermore, we conducted the LASSO regression analysis and obtained 4 BMRGs (MPV17, GNB1, DHX34, and MAFG) that were significantly related to the prognosis of LIHC patients. We further constructed a prognostic risk score model based on the above genes, which was verified to have good predictive performance for LIHC prognosis. In addition, we analyzed the correlation between the risk score and the tumor immune microenvironment (TIM), and the results showed that the high-risk scoring group tended to be in an immunosuppressed status. Finally, we investigated the relationship between the risk score and LIHC immune function. The results demonstrated that the risk score was closely related to the expression levels of multiple immune checkpoints. Patients in the low-risk group had significantly higher IPS scores, and patients in the high-risk group had lower immune escape and TIDE score. In conclusion, we established a novel risk model based on BMRGs, which may serve as a biomarker for prognosis and immunotherapy in LIHC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas/genética , Membrana Basal , Prognóstico , Microambiente Tumoral , RNA Helicases
6.
Mediators Inflamm ; 2023: 9810733, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37273451

RESUMO

Ferroptosis resistance is vital for B cell development, especially in inflammatory diseases, yet the underlying mechanism is still unclear. In this study, based on the scRNA-seq technique and flow cytometry, we discovered a proportion of neutrophils exhibited upregulated expression of the IL-6 and correlated with the expression of IL-6 receptor and SLC7A11 from B cells in lupus kidney. Moreover, we identified that in lupus kidney, neutrophils could provide IL-6 to facilitate ferroptosis resistance in B cells via SLC7A11, and inhibition of SLC7A11 could significantly enhance ferroptosis in B cells and could decrease B cell proliferation. This study helps understand the crosstalk between neutrophils and B cells in the kidney in the development of lupus.


Assuntos
Ferroptose , Interleucina-6 , Nefrite Lúpica , Humanos , Rim , Neutrófilos , Linfócitos B
7.
Kidney Int ; 102(3): 521-535, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35598813

RESUMO

Bruceine A is a natural quassinoid compound extracted from the fruit of the Traditional Chinese Medicine Brucea javanica (L.) Merr. that has various types of various biological activities. However, whether the compound has a protective effect on diabetic kidney disease remains unknown. Galectin-1 is actively involved in a variety of chronic inflammation-relevant human diseases including diabetic kidney disease. Here, we identified Bruceine A as a kidney protective molecule against a model of diabetic kidney disease in db/db mice with potent anti-inflammatory activity both in vitro and in vivo. Mechanistically, by selectively binding to the conserved carbohydrate-recognition domain of galectin-1 and disrupting the interaction between galectin-1 and the receptor for activated protein C kinase 1, Bruceine A was found to inhibit galectin-1-mediated inflammatory signal transduction under high glucose stress in rat mesangial HBZY-1 cells. Thus, our findings reveal Bruceine A as an unidentified galectin-1 inhibitor affording significant protection against diabetic kidney disease and may provide novel pharmacological therapeutics for the disease.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Quassinas , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/prevenção & controle , Galectina 1 , Humanos , Camundongos , Quassinas/química , Quassinas/farmacologia , Ratos
8.
Gastric Cancer ; 25(2): 346-359, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34724589

RESUMO

BACKGROUND: Cancer-associated fibroblasts (CAFs) are the most principal cells of depositing and remodeling extracellular matrix (ECM) within solid tumours. Both CAFs and ECM have been demonstrated to play critical roles in tumour development. However, the functional roles of CAFs-associated ECM or ECM remodeling in the pathogenesis of gastric cancer remain unclear. METHODS: Bioinformatics analysis of the differentially expressed genes between CAFs and corresponding normal fibroblasts (NFs) in gastric cancer was performed. The clinical relevance of hyaluronan and proteoglycan link protein 1 (HAPLN1) was investigated using TCGA data and human gastric cancer specimens. Spheroid cell invasion assay and nude mouse xenograft model were introduced to assay cell invasion. Second harmonic generation (SHG) was used to image and analyze the changes of collagen fibers in ECM. RESULTS: HAPLN1 was identified as the most significantly up-regulated gene in CAFs of gastric cancer, and higher HAPLN1 levels were associated with shorter overall survival. HAPLN1 was prominently produced by CAFs, and its levels were correlated positively with tumor T staging (P < 0.0001), lymph node metastasis (P = 0.0006) and TNM stage (P = 0.0063). Mechanically, gastric cancer cells activate fibroblasts to up-regulate HAPLN1 expression via activation of TGF-ß1/Smad2/3 signaling, which in turn promotes tumour migration and invasion. Importantly, SHG assays with mouse xenograft models and human samples further demonstrated CAFs-derived HAPLN1 increased tumour invasiveness through ECM remodeling. CONCLUSIONS: This study sheds light on the role of CAFs-derived HAPLN1 in the pathogenesis of gastric cancer, and provides insights for the development of novel strategies for prevention and treatment of gastric carcinoma.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Gástricas , Animais , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Fibroblastos/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Invasividade Neoplásica/patologia , Neoplasias Gástricas/patologia
9.
Appl Opt ; 61(35): 10380-10389, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36607096

RESUMO

The efficiency of a hollow beam received by the Cassegrain antenna coupling into a single-mode fiber is low, and converting the hollow beam into a solid beam can remarkably improve the coupling efficiency. In this paper, shaping diffractive optical elements (DOEs) are designed through a modified Gerchberg-Saxton algorithm (MGS) with Fresnel diffraction. Further, the MGS algorithm can be applicable in the issue of circular symmetric beam shaping. The properties of the system with/without shaping DOEs are analyzed and compared. According to the simulation results, in consideration of the energy loss of the antenna, DOEs, and coupling lens, the total transmission efficiency of the receiving antenna system at 1550 nm wavelength can reach 77.81%. In addition, the system with shaping DOEs can better adapt for coupling lenses with different focal lengths, and the variation of the maximum coupling efficiency of the DOEs shaping system at different focal lengths studied in this paper is within 2.00%, which is 6.73% lower than that of the lens shaping system. The research results provide an idea of reverse design for improving a coupling system, which can also provide inspiration for other optical system designs.

10.
Molecules ; 27(4)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35208940

RESUMO

A group of peptide metabolites (1-4), designated as mintaimycins, were isolated from Micromonospora sp. C-3509. The planar structures of mintaimycins were determined by combination of mass spectrometry, 1D and 2D NMR spectroscopy, and the stereochemistry of mintaimycins were partially resolved by Marfey's or Mosher's method. Mintaimycins featured a central ß-methylphenylalanine or phenylalanine linked at its amino group with 5-methyl-2-hexenoic acid, and at its carboxyl group with 5-hydroxy-norleucine or leucine that combined a derivative of hexanoic acid or 4-methylpentanoic acid. Mintaimycin A1 (1), the principal component, was found to exhibit the biological activity of inducing pre-adipocyte differentiation of 3T3-L1 fibroblast cells at 10.0 µmol/L.


Assuntos
Micromonospora , Peptídeos , Espectrometria de Massas , Micromonospora/química , Micromonospora/metabolismo , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos/química , Peptídeos/metabolismo
11.
Opt Express ; 29(15): 24561-24575, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34614698

RESUMO

A parallel bit-interleaved filter-bank multicarrier/offset quadrature amplitude modulation (FBMC/OQAM) security strategy based on four-dimensional chaos is proposed in this paper. After the QAM constellation point distribution is disturbed, the modulated FBMC bits and symbols are interleaved and encrypted to realize the improvement of the FBMC/OQAM system physical layer security performance. The chaotic sequence generated by the four-dimensional hyperchaotic system is optimized and calculated to control the disturbance process, which enhances the performance of the system against illegal malicious attacks. The parallel encryption scheme proposed in this scheme increases the encryption efficiency by 1.43 times; can provide a keyspace of 1090 size, which effectively resists brute force attacks; and improves the physical layer security of the system. The proposed FBMC/OQAM parallel bit interleaved encryption scheme using a 5 km weakly coupled four-mode fiber achieves a 3×10 Gb/s multiple-input multiple-output-free transmission. The experimental results show that this scheme can effectively improve the security performance of the system, and combines the few-mode multiplexing technology with advanced modulation. It is a candidate for the future large-capacity and high-security optical transmission system.

12.
J Cell Mol Med ; 24(12): 6750-6761, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32363730

RESUMO

Searching for the novel tumour biomarkers is pressing for gastric cancer diagnostication and prognostication. The serum specimens from patients diagnosed with locally advanced gastric carcinoma before operation and 4 week after surgery were collected, respectively, and serum proteome profiling was conducted by liquid chromatography-mass spectrometry (MS)/MS. Fifty-five proteins were identified to be up-regulated and 16 proteins were down-regulated, and these differentially expressed proteins participated in various biological processes. Serum levels of SOX3, one of down-regulated proteins, in stomach cancer patients were higher than in healthy controls. SOX3 levels in cancer tissues were remarkably related to tumour differentiation, lymph node metastasis, primary tumour invasion and pTNM (pathological TNM) stage. Analysis with The Cancer Genome Atlas database indicated that SOX3 level and pTNM stage were the independent risk factors for the patient survival and that the overall survival was negatively associated with the SOX3 levels. Loss-of-function showed that SOX3 promoted gastric cancer cell invasion and migration in vitro and in vivo. SOX3 silence inhibits the expression of MMP9, and SOX3 is responsible for MMP9 expression transcriptionally. Our study highlights the potentiality of the paired pre- and post-operation serum proteome signatures for the detection of biomarkers and reveals that SOX3 may serve as a candidate prognosis marker for gastric cancer.


Assuntos
Biomarcadores Tumorais/sangue , Proteoma/metabolismo , Proteômica , Fatores de Transcrição SOXB1/sangue , Neoplasias Gástricas/sangue , Movimento Celular , Regulação para Baixo , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
13.
Opt Express ; 28(14): 21236-21246, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32680168

RESUMO

In this article we have enhanced the security of an orthogonal frequency division multiplexed passive optical network (OFDM-PON) based on four dimensional (4D) encryption, including constellation, subcarrier, symbol and time, which is proposed for the first time in this paper. 4D-hyperchaotic mapping is used to generate four masking factors to achieve ultra-high security encryption in four different dimensions. During the encryption, dimension coordination optimization is adopted, which effectively reduces the time cost of the system and improves the encryption efficiency by 3 times. At the same time, probabilistic shaping (PS) technology is used to further optimize the system that has effectively improved the bit error performance by about 1 dB. The proposed encryption technique for OFDM-PON has been demonstrated successfully with the help of experiments. The generated OFDM signal is modulated by the quadrature amplitude modulation (QAM) technique, which transmitted 16 Gb/s data rate across a 25 km fiber span of standard single-mode fiber. The values of bit error rate (BER) and peak-to-average-power ratio (PAPR) are analyzed during the experiments, and the obtained results show that the proposed security-enhanced OFDM-PON has high sensitivity and security and can be well compatible with PS and OFDM technologies. The proposed scheme has very reliable security performance and also has excellent benefit improvement, which is very promising in the future PS-OFDM-PON.

14.
Chemistry ; 26(12): 2521-2528, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31692097

RESUMO

Hypoxia, as a crucial characteristic of cancer, has become an extremely significant direction for researchers to construct fluorescent probes for early diagnosis of tumors. Aggregation-induced emission fluorogens (AIEgens) possess many superior properties to those of conventional fluorophores due to aggregation-induced emission (AIE) features, such as a linear concentration-dependent increase in brightness, remarkable resistance to photobleaching, and the long-term tracking and imaging of cells. Constructing hypoxic response AIEgen-based probes will be very useful for the early diagnosis of tumors. Herein, several hypoxia-responsive probes based on AIEgens reported in the last three years are reported; these examples may lead to the construction of hypoxia-responsive AIE probes used for tumor hypoxia imaging in the future. In addition, typical, conventional hypoxia-responsive bioprobes are presented to further understand hypoxia-responsive fluorescent probes based on AIEgens.


Assuntos
Corantes Fluorescentes/química , Neoplasias/diagnóstico por imagem , Hipóxia Tumoral/fisiologia , Compostos Azo/química , Dimerização , Humanos , Imagem Óptica
15.
Acta Pharmacol Sin ; 41(1): 110-118, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31515527

RESUMO

In addition to the well-known cardiotonic effects, cardiac glycosides (CGs) produce potent anticancer effects with various molecular mechanisms. We previously show that ouabain induces autophagic cell death in human lung cancer cells by regulating AMPK-mediated mTOR and Src-mediated ERK1/2 signaling pathways. However, whether and how AMPK and Src signaling interacts in ouabain-treated cancer cells remains unclear. Given the pivotal role of AMPK in metabolism, whether ouabain affects cancer cell metabolism remains elusive. In this study we showed that treatment with ouabain (25 nM) caused simultaneous activation of AMPK and Src signaling pathways in human lung cancer A549 cells and human breast cancer MCF7 cells. Cotreatment with AMPK inhibitor compound C or siRNA greatly abrogates ouabain-induced Src activation, whereas cotreatment with Src inhibitor PP2 has little effect on ouabain-induced AMPK activity, suggesting that AMPK served as an upstream regulator of the Src signaling pathway. On the other hand, ouabain treatment greatly depletes ATP production in A549 and MCF7 cells, and supplement of ATP (100 µM) blocked ouabain-induced AMPK activation. We further demonstrated that ouabain greatly inhibited the mitochondrial oxidative phosphorylation (OXPHOS) in the cancer cells, and exerted differential metabolic effects on glycolysis depending on cancer cell type. Taken together, this study reveals that the altered cancer cell metabolism caused by ouabain may contribute to AMPK activation, as well as its cytotoxicity towards cancer cells.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cardiotônicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Ouabaína/farmacologia , Transdução de Sinais/efeitos dos fármacos , Quinases da Família src/metabolismo , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Trifosfato de Adenosina/antagonistas & inibidores , Trifosfato de Adenosina/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosforilação/efeitos dos fármacos , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Quinases da Família src/antagonistas & inibidores
16.
J Cell Mol Med ; 23(1): 293-305, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30394687

RESUMO

Gastric cancer (GC) is a malignancy of the lining of the stomach and is prone to distant metastasis, which involves a variety of complex molecules. The S100 proteins are a family of calcium-binding cytosolic proteins that possess a wide range of intracellular and extracellular functions and play pivotal roles in the invasion and migration of tumour cells. Among these, S100A10 is known to be overexpressed in GC. Lysine succinylation, a recently identified form of protein post-translational modification, is an important regulator of cellular processes. Here, we demonstrated that S100A10 was succinylated at lysine residue 47 (K47), and levels of succinylated S100A10 were increased in human GC. Moreover, K47 succinylation of S100A10 was stabilized by suppression of ubiquitylation and subsequent proteasomal degradation. Furthermore, carnitine palmitoyltransferase 1A (CPT1A) was found to function as a lysine succinyltransferase that interacts with S100A10. Succinylation of S100A10 is regulated by CPT1A, while desuccinylation is regulated by SIRT5. Overexpression of a succinylation mimetic mutant, K47E S100A10, increased cell invasion and migration. Taken together, this study reveals a novel mechanism of S100A10 accumulation mediated by succinylation in GC, which promotes GC progression and is regulated by the succinyltransferase CPT1A and SIRT5-mediated desuccinylation.


Assuntos
Anexina A2/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Proteínas S100/metabolismo , Neoplasias Gástricas/patologia , Animais , Anexina A2/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Lisina/metabolismo , Masculino , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Processamento de Proteína Pós-Traducional , Proteínas S100/genética , Sirtuínas/metabolismo , Neoplasias Gástricas/metabolismo , Succinatos/metabolismo
17.
Anal Bioanal Chem ; 411(5): 1041-1052, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30613842

RESUMO

The great hurdles related with matrix-assisted laser desorption/ionization (MALDI) analysis are inhomogeneous crystallization, poor reproducibility, and low sensitivity. To effectively improve the performance of MALDI mass spectrometry (MS), graphene oxide (GO) was first utilized as an auxiliary matrix of the conventional matrices, including 2,5-dihydroxybenzoic acid (DHB), α-cyano-4-hydoxycyanocinnamic acid (CHCA), 2,4,6-trihydroxyacetophenone (THAP), and 3,5-dimethoxy-4-hydroxycinnamic acid (SA), for the analysis of small molecules and biological macromolecules on different MALDI MS systems. The results revealed that the DHB-GO composite matrix could provide much superior crystal homogenization, better reproducibility, higher sensitivity, and more excellent linearity for the statins' tissue imaging on iMScope than the single-use DHB matrix. Moreover, the DHB-GO dramatically improved the spot-to-spot and shot-to-shot reproducibility, crystal homogenization, sensitivity, and linearity of MALDI-TOF MS for statins' analysis in dried droplet. The capability of THAP on the analysis of lipids, similarly, could be greatly enhanced by the combined use of GO. THAP-GO composite matrix was expected to be widely used in the MALDI MS-based liposome studies. It was also found that CHCA-GO could provide superior analytical performance for peptides. The sensitivity and reproducibility of intact proteins could be greatly improved by SA-GO composite matrix. More importantly, the better reproducibility produced by the composite matrices sufficiently indicated that low concentration (0.1 mg mL-1) of GO almost did not cause contamination to MALDI MS system. Thus, GO was proved to be a versatile auxiliary matrix for the MALDI MS-based routine analysis of small molecules and biological macromolecules. Graphical abstract ᅟ.


Assuntos
Grafite/química , Lipídeos/análise , Peptídeos/análise , Proteínas/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Acetofenonas/química , Animais , Ácidos Cumáricos/química , Cristalização , Gentisatos/química , Fígado/química , Masculino , Camundongos Endogâmicos BALB C , Somatostatina/análise
18.
Acta Pharmacol Sin ; 40(5): 699-709, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30218071

RESUMO

The combinational administration of antioxidants and chemotherapeutic agents during conventional cancer treatment is among one of the most controversial areas in oncology. Although the data on the combinational usage of doxorubicin (DOX) and glutathione (GSH) agents have been explored for over 20 years, the duration, administration route, and authentic rationality have not yet been fully understood yet. In the current study, we systematically investigated the pharmacokinetics (PK) and pharmacodynamics (PD) with both in vivo and in vitro models to elucidate the influence of GSH on the toxicity and efficacy of DOX. We first studied the cardioprotective and hepatoprotective effects of GSH in Balb/c mice, H9c2, and HL7702 cells. We showed that coadministration of exogenous GSH (5, 50, and 500 mg/kg per day, intragastric) significantly attenuated DOX-induced cardiotoxicity and hepatotoxicity by increasing intracellular GSH levels, whereas the elevated GSH concentrations did not affect the exposure of DOX in mouse heart and liver. From PK and PD perspectives, then the influences of GSH on the chemotherapeutic efficacy of DOX were investigated in xenografted nude mice and cancer cell models, including MCF-7, HepG2, and Caco-2 cells, which revealed that administration of exogenous GSH dose-dependently attenuated the anticancer efficacy of DOX in vivo and in vitro, although the elevated GSH levels neither influenced the concentration of DOX in tumors in vivo, nor the uptake of DOX in MCF-7 tumor cells in vitro. Based on the results we suggest that the combined administration of GSH and DOX should be contraindicated during chemotherapy unless DOX has caused serious hepatotoxicity and cardiotoxicity.


Assuntos
Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Cardiotônicos/uso terapêutico , Cardiotoxicidade/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doxorrubicina/uso terapêutico , Glutationa/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Cardiotônicos/administração & dosagem , Cardiotônicos/farmacocinética , Linhagem Celular Tumoral , Contraindicações de Medicamentos , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Doxorrubicina/toxicidade , Quimioterapia Combinada , Glutationa/administração & dosagem , Glutationa/farmacocinética , Xenoenxertos , Humanos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Miocárdio/metabolismo , Ratos , Distribuição Tecidual
19.
Sci Technol Adv Mater ; 20(1): 870-875, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489056

RESUMO

Liquid-phase exfoliated graphene sheets are promising candidates for printing electronics. Here, a high-performance printed 2.4 GHz graphene-based antenna is reported. Graphene conductive ink prepared by using liquid-phase exfoliation process is printed onto a water-transferable paper by using blade printing technique, which is then patterned as dipole antenna and transferred onto a target substrate. The fabricated dipole antenna (43 × 3 mm), exhibiting typical radiation patterns of an ideal dipole antenna, achieves -10 dB bandwidth of 8.9% and a maximum gain of 0.7 dBi. The printed graphene-antennas satisfy the application requirements of the Internet of Things and suggest its feasibility of replacing conventional metallic antennas in those applications.

20.
Plant Physiol ; 174(2): 875-885, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28400493

RESUMO

Virus-induced flowering (VIF) uses virus vectors to express Flowering Locus T (FT) to induce flowering in plants. This approach has recently attracted wide interest for its practical applications in accelerating breeding in crops and woody fruit trees. However, the insight into VIF and its potential as a powerful tool for dissecting florigenic proteins remained to be elucidated. Here, we describe the mechanism and further applications of Potato virus X (PVX)-based VIF in the short-day Nicotiana tabacum cultivar Maryland Mammoth. Ectopic delivery of Arabidopsis (Arabidopsis thaliana) AtFT by PVX/AtFT did not induce the expression of the endogenous FT ortholog NtFT4; however, it was sufficient to trigger flowering in Maryland Mammoth plants grown under noninductive long-day conditions. Infected tobacco plants developed no systemic symptoms, and the PVX-based VIF did not cause transgenerational flowering. We showed that the PVX-based VIF is a much more rapid method to examine the impacts of single amino acid mutations on AtFT for floral induction than making individual transgenic Arabidopsis lines for each mutation. We also used the PVX-based VIF to demonstrate that adding a His- or FLAG-tag to the N or C terminus of AtFT could affect its florigenic activity and that this system can be applied to assay the function of FT genes from heterologous species, including tomato (Solanum lycopersicum) SFT and rice (Oryza sativa) Hd3a Thus, the PVX-based VIF represents a simple and efficient system to identify individual amino acids that are essential for FT-mediated floral induction and to test the ability of mono- and dicotyledonous FT genes and FT fusion proteins to induce flowering.


Assuntos
Proteínas de Arabidopsis/genética , Flores/genética , Regulação da Expressão Gênica de Plantas , Nicotiana/virologia , Potexvirus/genética , Substituição de Aminoácidos , Flores/virologia , Solanum lycopersicum/genética , Solanum lycopersicum/virologia , Oryza/genética , Oryza/virologia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Nicotiana/genética
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