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1.
Environ Sci Pollut Res Int ; 31(36): 49026-49039, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39042189

RESUMO

Heavy metal pollution poses a serious threat to crops growth and yield. Recently, nanoparticles (NPs) have emerged as a promising strategy to mitigate the negative effect of heavy metal on crop growth. This study investigated the beneficial effects of copper oxide nanoparticles (CuO NPs) on the morphological and physiological-biochemical traits of rice seedlings (Oryza sativa L.) under cadmium (Cd) stress. The results demonstrated that the application of CuO NPs increased the contents of nutrition elements in shoots and roots as well as photosynthetic pigments, consequently improving the growth of rice seedlings under Cd stress, especially at low level of Cd stress. Meanwhile, CuO NPs obviously decreased the Cd accumulation in the rice seedlings and immobilized Cd in less toxic chemical forms and subcellular compartments. Moreover, CuO NPs modulated the antioxidant system, ameliorating oxidative damage and membrane injury caused by Cd. Multivariate analysis established correlations between physio-biochemical parameters and further revealed the mitigation of Cd damage to rice seedlings by CuO NPs was associated with inhibition Cd accumulation, altering Cd chemical form and subcellular distribution, increasing the contents of mineral nutrients, photosynthetic pigments and secondary metabolites and antioxidant enzyme activities, and reducing oxidative damage. Overall, the present study indicated that CuO NPs could effectively reduce the Cd toxicity to rice seedlings, demonstrating their potential application in agricultural production.


Assuntos
Cádmio , Cobre , Oryza , Plântula , Oryza/efeitos dos fármacos , Cádmio/toxicidade , Cobre/toxicidade , Plântula/efeitos dos fármacos , Poluentes do Solo/toxicidade , Nanopartículas Metálicas/toxicidade , Nanopartículas
2.
Aging (Albany NY) ; 16(7): 5929-5948, 2024 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-38535990

RESUMO

Study finds that eukaryotic translation initiation factor 3 subunit D (EIF3D) may play an important role in aberrant alternative splicing (AS) events in tumors. AS possesses a pivotal role in both tumour progression and the constitution of the tumour microenvironment (TME). Regrettably, our current understanding of AS remains circumscribed especially in the context of immunogene-related alternative splicing (IGAS) profiles within Head and Neck Squamous Cell Carcinoma (HNSC). In this study, we comprehensively analyzed the function and mechanism of action of EIF3D by bioinformatics analysis combined with in vitro cellular experiments, and found that high expression of EIF3D in HNSC was associated with poor prognosis of overall survival (OS) and progression-free survival (PFS). The EIF3D low expression group had a higher degree of immune infiltration and better efficacy against PD1 and CTLA4 immunotherapy compared to the EIF3D high expression group. TCGA SpliceSeq analysis illustrated that EIF3D influenced differentially spliced alternative splicing (DSAS) events involving 105 differentially expressed immunogenes (DEIGs). We observed an induction of apoptosis and a suppression of cell proliferation, migration, and invasion in EIF3D knock-down FaDu cells. RNA-seq analysis unveiled that 531 genes exhibited differential expression following EIF3D knockdown in FaDu cells. These include 52 DEIGs. Furthermore, EIF3D knockdown influenced the patterns of 1923 alternative splicing events (ASEs), encompassing 129 IGASs. This study identified an RNA splicing regulator and revealed its regulatory role in IGAS and the TME of HNSC, suggesting that EIF3D may be a potential target for predicting HNSC prognosis and immunotherapeutic response.


Assuntos
Processamento Alternativo , Fator de Iniciação 3 em Eucariotos , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Fator de Iniciação 3 em Eucariotos/genética , Fator de Iniciação 3 em Eucariotos/metabolismo , Processamento Alternativo/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Prognóstico , Apoptose/genética , Masculino , Movimento Celular/genética , Feminino
3.
Food Chem ; 444: 138585, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38335680

RESUMO

This study aimed to synthesize a novel emulsifier, hyaluronic acid-poly(glyceryl)10-stearate (HA-PG10-C18), and employ it for the fabrication of nanoemulsions incorporating deep-sea fish oil to improve their apparent solubility and physicochemical stability. 1H NMR and FT-IR analyses indicated successful synthesis of HA-PG10-C18. Nanoemulsions of deep-sea fish oil loaded with HA-PG10-C18 (HA-PG10-C18@NE) were successfully fabricated by ultrasonic emulsification. The fixed aqueous layer thickness (FALT) of PG10-C18@NE and HA-PG10-C18@NE was determined and the FALT of both nanoemulsions was similar, while the surface density of HA-PG10-C18@NE (4.92 × 10-12 ng/nm2) is 60 % higher than that of PG10-C18@NE (3.07 × 10-12 ng/nm2). Notably, HA-PG10-C18@NE demonstrated an exceptional physicochemical stability when exposed to various stressed environmental conditions, especially its freeze-thaw stability. Moreover, after simulated in vitro digestion, the HA-PG10-C18@NE exhibited a comparatively greater liberation of free fatty acids (94.0 ± 1.7 %) when compared to the release observed in PG10-C18@NE (85.5 ± 2.2 %).


Assuntos
Óleos de Peixe , Estearatos , Ácido Hialurônico , Emulsões/química , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Diagn Pathol ; 18(1): 123, 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37951919

RESUMO

BACKGROUND: With the continuous discovery of new borderline thyroid lesions and benign and malignant "gray areas", coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. METHODS: In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. RESULTS: Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher. CONCLUSIONS: The results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue.


Assuntos
Adenoma , Carcinoma Papilar , Disgenesia da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico , Ciclina D1 , Hiperplasia , Diagnóstico Diferencial , Carcinoma Papilar/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias da Glândula Tireoide/patologia , Adenoma/patologia , Disgenesia da Tireoide/diagnóstico
5.
Pestic Biochem Physiol ; 195: 105581, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37666606

RESUMO

Anthracnose decay caused by Colletotrichum gloeosporioides greatly shortens the shelf life and commercial quality of mango fruit. Putrescine (1,4-Diaminobutane) is involved in modulating plant defense to various environmental stresses. In this research, in vivo and in vitro tests were used to explore the antifungal activity and the underlying mechanism of putrescine against C. gloeosporioides in mango fruit after harvested. In vivo tests suggested that putrescine markedly delayed the occurrence of disease and limited the spots expansion on inoculated mango fruit. Further analysis exhibited that putrescine treatment enhanced disease resistance, along with enhanced activities of chitinase (CHI), ß-1,3-glucanase (GLU), phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate coenzyme A ligase (4CL), polyphenol oxidase (PPO) and the accumulation of lignin, flavonoid, phenolics, and anthocyanin in infected mango fruit. In addition, in vitro tests showed that putrescine exerted strongly antifungal activity against C. gloeosporioides. Putrescine induced the production of reactive oxygen species (ROS) and severe lipid peroxidation damage in C. gloeosporioides mycelia, resulting in the leakage of soluble protein, soluble sugar, nucleic acids, K+ and Ca2+ of C. gloeosporioides mycelia. The mycelium treated with putrescine showed severe deformity and shrinkage, and even cracking. Taken together, putrescine could effectively reduce the incidence rate and severity of anthracnose disease possibly through direct fungicidal effect and indirect induced resistance mechanism, thus showing great potential to be applied to disease control.


Assuntos
Fungicidas Industriais , Mangifera , Antifúngicos/farmacologia , Putrescina/farmacologia , Frutas , Fungicidas Industriais/farmacologia
6.
Sci Total Environ ; 877: 162784, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36906019

RESUMO

The present study investigated the potential of diatomite addition in enhancing sludge settlement of two-stage PN/Anammox for real reject water treatment, with a focus on sludge settling velocity, nitrogen removal capacity, sludge morphological features, and microbial community changes. The study found that diatomite addition significantly improved the sludge settleability of the two-stage PN/A process, resulting in a decrease in sludge volume index (SVI) from 70 to 80 mL/g to about 20-30 mL/g for both PN and Anammox sludge, although the sludge-diatomite interaction differed between the two types of sludge. In the PN sludge, diatomite acted as a carrier, while in the Anammox sludge, it acted as micro-nuclei. The addition of diatomite also increased the biomass amounts in the PN reactor, with a 5-29 % improvement attributed to its role as a biofilm carrier. The effects of diatomite addition on sludge settleability were more prominent at high mixed liquor suspended solids (MLSS), where sludge characteristics were deteriorated. Furthermore, the settling rate of the experimental group consistently exceeded that of the blank group after diatomite addition, with a significant decrease in SV. The relative abundance of Anammox bacteria was improved, and sludge particle size decreased in the diatomite-added Anammox reactor. Diatomite was effectively retained in both reactors, with less loss observed for Anammox than PN due to its more tightly wrapped structure, resulting in a stronger sludge-diatomite interaction. Overall, the results of this study suggest that diatomite addition has potential in enhancing the settling properties and performance of two-stage PN/Anammox for real reject water treatment.


Assuntos
Compostos de Amônio , Purificação da Água , Esgotos/microbiologia , Oxidação Anaeróbia da Amônia , Reatores Biológicos/microbiologia , Nitrogênio , Oxirredução , Desnitrificação
7.
Front Cardiovasc Med ; 9: 948561, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061556

RESUMO

Background: Obesity as a risk factor of heart disease (HD) is confirmed through observational, laboratory, and intervention studies. However, it cannot explain why HD declines, but obesity increases in the United States in recent decades. This study attempted to understand this paradox. Methods: Annual data of national HD mortality (1999-2018) were derived from Wide-Ranging Online Data for Epidemiologic Research, biannual obesity data (1999-2016) from the National Health and Nutrition Examination Survey, and smoking data (1965-1990) were from the National Health Interview Survey. Age-period-cohort method was used to decompose HD mortality into age, period, and cohort effects, and to estimate age-cohort adjusted mortality rates. To explain the paradox, age-cohort adjusted rates were associated with obesity rates to verify the positive obesity-HD relationship, while smoking rates were associated with cohort effects to explain the current declines in HD mortality. Results: During 1999-2018, the prevalence of obesity increased while the crude HD mortality rate declined for both sex and all races. After controlling for the curvilinear age effect and consistent declining cohort effect, the age-cohort adjusted HD mortality sustained stable in 1999-2007 and increased thereafter. The age-cohort adjusted rate in 1999-2018 (per 100,000) increased from 189.31 to 238.56 for males, 67.23 to 90.28 for females, 115.54 to 157.39 for White, 246.40 to 292.59 for Black, 79.79 to 101.40 for Hispanics, and 49.95 to 62.86 for Asian. The age-cohort adjusted HD mortality rates were positively associated with obesity rates (r = 0.68 for males, 0.91 for females, 0.89 for White, and 0.69 for Hispanic, p < 0.05), but not significant for Black and Asian. Further, during 1965-1990, the estimated cohort effect showed a decline in HD risk and was positively associated with smoking rates (r = 0.98 for both sex, 0.99 for White, and 0.98 for Black, p < 0.01). Conclusion: Study findings reveal potential increase of HD risk and support the positive relationship between obesity and HD risk. Declines in HD mortality in the past two decades are primarily due to tobacco use reduction and this protective effect was entangled in the mortality rates as cohort effect.

8.
J Cell Mol Med ; 25(22): 10638-10649, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34697906

RESUMO

Cancer treatment has gradually developed from toxic chemotherapy to targeted therapy with fewer side effects. Approximately 30% of breast cancer patients overexpress human epidermal growth factor receptor 2 (HER-2). Previous studies have successfully produced single-chain antibodies (scFv) targeting HER-2+ breast cancer; however, scFv have poor stability, easy aggregation and a shorter half-life, which have no significant effect on targeting therapy. Moreover, scFv has been considered as a drug delivery platform that can kill target cells by effector molecules. However, the functional killing domains of immunotoxins are mainly derived from plant or bacterial toxins, which have a large molecular weight, low tissue permeability and severe side effects. To address these concerns, we designed several apoptotic immune molecules to replace exogenous toxins using endogenous apoptosis-related protein DNA fragmentation factor 40 (DFF40) and tandem-repeat Cytochrome c base on caspase-3 responsive peptide (DEVD). Our results suggest that DFF40 or Cytc fusion scFv specifically targets HER-2 overexpressing breast cancer cells (SK-BR-3 and BT-474) rather than HER-2 negative cells (MDA-MB-231 and MCF-7). Following cellular internalization, apoptosis-related proteins inhibited tumour activity by initiating endogenous apoptosis pathways, which significantly reduced immunogenicity and toxic side effects. Therefore, we suggest that immunoapoptotic molecules may become potential drugs for targeted immunotherapy of breast cancer.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Proteínas Recombinantes de Fusão/farmacologia , Animais , Especificidade de Anticorpos , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/genética , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Ordem dos Genes , Humanos , Camundongos , Plasmídeos/genética , Receptor ErbB-2/imunologia , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Int Immunopharmacol ; 100: 108107, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34482265

RESUMO

Activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome plays a crucial role in the inflammatory responses of monosodium urate (MSU) crystal-induced gouty arthritis. Therefore, the molecular basis of NLRP3 inflammasome is very valuable in developing potential therapeutic drugs for gout. Tetrahydropalmatine (THP), the main active component of the traditional Chinese medicinal herb Corydalis yanhusuo, has shown prominent anti-inflammatory and analgesic activities, but to date, these effects have not been investigated exhaustively on gout. This study indicated that THP attenuated pain and swelling in an MSU-induced acute gout model by decreasing pro-inflammatory cytokine production and inflammatory cell infiltration. THP exerted its actions by suppressing NLRP3 inflammasome activation and subsequent formation of caspase-1. Furthermore, results showed that THP alleviated MSU-induced reactive oxygen species (ROS) generation, upstream of NLRP3 inflammasome activation, by an increase in the activities of antioxidant enzymes both in vitro and in vivo. In conclusion, our study suggests that THP suppressed ROS-mediated NLRP3 inflammasome activation in MSU-induced inflammatory responses, which highlights its therapeutic potential in gouty arthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Artrite Gotosa/prevenção & controle , Alcaloides de Berberina/farmacologia , Inflamassomos/metabolismo , Articulações/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Analgésicos/farmacologia , Animais , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/imunologia , Artrite Gotosa/metabolismo , Caspase 1/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Articulações/imunologia , Articulações/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Transdução de Sinais , Ácido Úrico
10.
Nat Prod Res ; 35(11): 1869-1873, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31305144

RESUMO

In the course of searching for cytotoxic metabolites from insects associated actinomyces, two new natural p-terphenyl glycosides, strepantibin D (1) and strepantibin E (2), along with terferol (3), actinomycin D (4), actinomycin V (5) and actinomycin V0ß (6), were identified from the fermentation medium of a Streptomyces sp. which was obtained from the larva body of mud dauber wasp. Strepantibin D (1), previously reported as a synthetic derivative of terfestatin A, is firstly isolated as a natural p-terphenyl in this research. Strepantibin D (1) and terferol (3) showed medium cytotoxic activity against breast cancer cells MCF-7, MDA-MB-231 and BT-474. Actinomycins (4-6), especially actinomycin V (5), displayed remarkable cytotoxicity against breast cancer cells, with IC50 values ranging from 0.83 nM to 369.90 nM.


Assuntos
Dactinomicina/farmacologia , Streptomyces/química , Compostos de Terfenil/farmacologia , Vespas/microbiologia , Animais , Antineoplásicos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dactinomicina/química , Humanos , Larva/microbiologia , Compostos de Terfenil/química
11.
ACS Omega ; 5(25): 15077-15082, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32637780

RESUMO

To find a facile way to produce a hydrophobic sponge that can effectively absorb oils is urgent to resolve the environmental pollution and ecological disaster caused by oil spillage. Here, alkylated carbon dots (C dots) were prepared from pyrolysis of a mixture of dodecylamine and citric acid followed by purification through silica gel column chromatography. Polyurethane sponge was modified by alkylated C dots by a simple dip-coating method, which endows the photoluminescent and hydrophobic sponge with good absorption capacities for various oils and nonpolar organic solvents with high recyclability. The water contact angle of the modified sponge can reach 138.8°. Interestingly, the sponge enables visual absorption under UV irradiation in the dark, which has not been achieved by other carbon-based adsorbents. The sponge was further made ferromagnetic by introducing alkylated Fe3O4 nanoparticles into its structure, which allowed controllable oil-water separation.

12.
Cancer Sci ; 111(10): 3802-3812, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32691974

RESUMO

Baicalein, a flavonoid phytochemical, has been shown to be effective as an anti-metastatic agent for various cancers, especially for non-small-cell lung cancer (NSCLC). However, the underlying mechanism of how baicalein targets cellular processes during NSCLC cell invasion and metastasis remains elusive. In this study, we found that non-cytotoxic concentrations of baicalein still retained anti-dissemination activity both in vitro and in vivo. Using a genetic encoding tension probe based on Förster resonance energy transfer (FRET) theory, baicalein was shown to significantly decrease ezrin tension by downregulating cellular ezrin S-nitrosylation (SNO) levels in NSCLC cells in the inflammatory microenvironment. Decreased ezrin tension inhibited the formation of an aggressive phenotype of NSCLC cell and leader cell in collective migration, and subsequently suppressed NSCLC dissemination. Baicalein restrained SNO-mediated ezrin tension by decreasing iNOS expression levels. Overall this study demonstrates the novel mechanism used by baicalein to suppress NSCLC invasion and metastasis from a mechanopharmacology perspective and illustrates a new direction for drug development.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas do Citoesqueleto/metabolismo , Flavanonas/farmacologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Proteínas do Citoesqueleto/genética , Modelos Animais de Doenças , Flavanonas/química , Humanos , Masculino , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Óxido Nítrico Sintase Tipo II/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Proteomics ; 20(12): e1900255, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32419311

RESUMO

The recent development and implementation of the advanced peak determination (APD) algorithm with MS instrument dramatically increased the sampling of low abundance features for MS/MS fragmentation. After in-depth evaluation, it is found that with APD on, many chimeric spectra are acquired through co-fragmentation of high abundance contaminants with low abundance targets, and such co-fragmentations are largely avoided when APD is off. To evaluate whether such a co-fragmentation could significantly distort the accuracy of the isobaric-labeling based quantitation of the low abundance target, a single-shot TMT experiment is performed using a two-proteome model, whereby each TMT channel contains premixed peptides from human and a cyanobacterium with a known ratio. Unexpectedly, it is found that APD does not significantly distort TMT ratios, probably because the majority of the APD-specific chimeric spectra are not identifiable. Nevertheless, a few examples of significant distortion of TMT ratios of low abundance peptides caused by APD is found through manual inspection, and suggests that APD should be off in a single-shot TMT experiment to avoid the laborious and time-costing manual inspection.


Assuntos
Marcação por Isótopo/métodos , Peptídeos/análise , Proteoma/análise , Proteômica/métodos , Proteínas de Bactérias/análise , Proteínas de Bactérias/metabolismo , Cromatografia Líquida/métodos , Células HEK293 , Humanos , Peptídeos/metabolismo , Proteoma/metabolismo , Reprodutibilidade dos Testes , Synechocystis/metabolismo , Espectrometria de Massas em Tandem/métodos
14.
Mar Drugs ; 17(5)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075906

RESUMO

Four angucycline glycosides were previously characterized from marine-derived Streptomyces sp. OC1610.4. Further investigation of this strain cultured on different fermentation media from that used previously resulted in the isolation of two new angucycline glycosides, vineomycins E and F (1-2), and five known homologues, grincamycin L (3), vineomycinone B2 (4), fridamycin D (5), moromycin B (7), and saquayamycin B1 (8). Vineomycin F (2) contains an unusual ring-cleavage deoxy sugar. All the angucycline glycosides isolated from Streptomyces sp. OC1610.4 were evaluated for their cytotoxic activity against breast cancer cells MCF-7, MDA-MB-231, and BT-474. Moromycin B (7), saquayamycin B1 (8), and saquayamycin B (9) displayed potent anti-proliferation against the tested cell lines, with IC50 values ranging from 0.16 to 0.67 µM. Saquayamycin B (9) inhibited the migration and invasion of MDA-MB-231 cells in a dose-dependent manner, as detected by Transwell and wound-healing assays.


Assuntos
Antineoplásicos/farmacologia , Glicosídeos/farmacologia , Antraciclinas/farmacologia , Antraquinonas/farmacologia , Antineoplásicos/química , Neoplasias da Mama , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Concentração Inibidora 50 , Células MCF-7 , Estrutura Molecular , Streptomyces/metabolismo
15.
J Nat Prod ; 82(5): 1114-1119, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31013087

RESUMO

Two new p-terphenyls, strepantibins A and B (1 and 2), along with the first representative of a naturally occurring bisphenyltropone, strepantibin C (3), were characterized from a Streptomyces sp. associated with the larvae of the mud dauber wasp Sceliphron madraspatanum. Their structures were determined by high-resolution electrospray ionization mass spectrometry, NMR, and X-ray crystallography data interpretation. Strepantibins A-C inhibited hexokinase II (HK2) activity and displayed antiproliferative activity against hepatoma carcinoma cells HepG-2, SMMC-7721 and plc-prf-5. In SMMC-7721 cells treated with strepantibin A, the morphological characteristics of apoptosis were observed.


Assuntos
Antineoplásicos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Hexoquinase/antagonistas & inibidores , Streptomyces/química , Vespas/microbiologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray
16.
Onco Targets Ther ; 10: 5297-5302, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29158681

RESUMO

BACKGROUND: Although the associations between common single nucleotide polymorphisms (SNPs) of EFEMP1 gene and glioma risk have been investigated in Chinese population-based case-control studies, investigation results for several SNPs are inconsistent. In addition, the single-center study has a poor statistical power due to finite sample size. Therefore, a meta-analysis was conducted to comprehensively determine the associations. METHODS: All eligible case-control studies were obtained by searching PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the associations in fixed- or random-effects model. RESULTS: EFEMP1 rs1346787 polymorphism was significantly associated with glioma risk in Chinese population under all genetic models (GG vs AA, OR =2.22, 95% CI =1.46-3.36; AG vs AA, OR =1.54, 95% CI =1.27-1.87; (GG+AG) vs AA, OR =1.60, 95% CI =1.34-1.93; GG vs (AG+AA), OR =1.86, 95% CI =1.24-2.78; G vs A, OR =1.54, 95% CI =1.32-1.79). However, the significant association of EFEMP1 rs1346786 with glioma risk in Chinese population was observed only under heterozygous model of AG vs AA (OR =1.34, 95% CI =1.10-1.62), dominant model of (GG+AG) vs AA (OR =1.36, 95% CI =1.13-1.63), and allelic model of G vs A (OR =1.28, 95% CI =1.10-1.50). CONCLUSION: Our study demonstrated that EFEMP1 polymorphisms, especially rs1346787 and rs1346786, might predict glioma risk in Chinese population. However, high-quality case-control studies with larger sample sizes are warranted to confirm the above-mentioned findings.

17.
J Cell Biochem ; 118(11): 3943-3952, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28398610

RESUMO

Radioprotection is an important approach to reduce the side-effects of radiotherapy. The radioprotective effect of the flavonoids of Rosa roxburghii Tratt (FRT) has been confirmed, and the mechanism has been identified as theBcl-2/caspase-3/PARP-1 signaling pathway. In this study, we investigated the effects of FRT on the intercellular adhesion molecule (ICAM), and vascular cell adhesion protein (VCAM) in addition to apoptosis-related proteins such as Bax/Bcl-2, p-ERK/ERK, p-p53/p53, and p-p38/p38. In the present study, we focused on the effect of FRT on PARP-1/AIF. Ionizing radiation triggered the activation of PARP-1 and AIF translocation from the mitochondrion to the nucleus. The inhibition of PARP-1/AIF signaling pathway by FRT was investigated. Our results showed that the expressions of Bax/Bcl-2, p-ERK/ ERK, p-p53/p53, and p-p38/p38 were decreased after FRT treatment compared with the radiation-treated group. FRT inhibited PARP-1 activation to inhibit AIF translocation from mitochondrion to nucleus. Pretreatment with FRT diminished the comet's tail and reduced fragments in six Gy-irradiated thymocytes compared with the irradiated cells without FRT treatment. We conclude that FRT enhanced radioprotection at least partially by regulating PARP-1/AIF to reduce apoptosis. J. Cell. Biochem. 118: 3943-3952, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Fator de Indução de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Núcleo Celular/metabolismo , Flavonoides/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Rosa/química , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Núcleo Celular/patologia , Flavonoides/química , Masculino , Camundongos
18.
Eur J Pharmacol ; 795: 66-74, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27916554

RESUMO

Radiotherapy is one of the most effective non-surgical treatments for many tumors. However, radiation damage remains a major negative consequence of radiotherapy. At present, radio-protective effect of troxerutin has been confirmed, but the mechanism of this radioprotection has not been elucidated. Here, this study showed that troxerutin protected thymus tissue of irradiated mice, and its radio-protective effect on thymocytes was significant in the range of 0.625-10µg/ml. Troxerutin significantly inhibited apoptosis of irradiated thymocytes at the concentration of 10µg/ml. Computer-aided drug design was used to investigate potential candidate targets for troxerutin, and an excellent correlation was identified between troxerutin and AKT (Pharm mapper and KEGG signal pathway). Troxerutin inhibited the activation of PTEN to stimulate AKT, which in turn prevented the activation of JNK to protect cells. Our results showed that troxerutin enhanced radioprotection at least partially by activating AKT to inhibit the activation of JNK.


Assuntos
Hidroxietilrutosídeo/análogos & derivados , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Protetores contra Radiação/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/efeitos da radiação , Hidroxietilrutosídeo/farmacologia , Masculino , Camundongos , Timo/efeitos dos fármacos , Timo/patologia , Timo/efeitos da radiação
19.
Apoptosis ; 21(10): 1125-43, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27401922

RESUMO

The objective of our study was to assess the radioprotective effect of flavonoids extracted from Rosa roxburghii Tratt (FRT) and investigate the role of Bcl-2(Ca(2+))/Caspase-3/PARP-1 pathway in radiation-induced apoptosis. Cells and mice were exposed to (60)Co γ-rays at a dose of 6 Gy. The radiation treatment induced significant effects on tissue pathological changes, apoptosis, Ca(2+), ROS, DNA damage, and expression levels of Bcl-2, Caspase-3 (C-Caspase-3), and PARP-1. The results showed that FRT acted as an antioxidant, reduced DNA damage, corrected the pathological changes of the tissue induced by radiation, promoted the formation of spleen nodules, resisted sperm aberration, and protected the thymus. FRT significantly reduced cell apoptosis compared with the irradiation group. The expression of Ca(2+) and C-Caspase-3 was decreased after FRT treatment compared with the radiation-treated group. At the same time, expression of prototype PARP-1 and Bcl-2 increased, leading to a decrease in the percentage of apoptosis cells in FRT treatment groups. We conclude that FRT acts as a radioprotector. Apoptosis signals were activated via the Bcl-2(Ca(2+))/Caspase-3/PARP-1 pathway in irradiated cells and FRT inhibited this pathway of apoptosis by down-regulation of C-Caspase-3 and Ca(2+) and up-regulation of prototype PARP-1 and Bcl-2.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Flavonoides/administração & dosagem , Extratos Vegetais/administração & dosagem , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Protetores contra Radiação/administração & dosagem , Rosa/química , Animais , Apoptose/efeitos da radiação , Caspase 3/genética , Raios gama , Humanos , Masculino , Camundongos , Poli(ADP-Ribose) Polimerase-1/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética
20.
Zhongguo Zhong Yao Za Zhi ; 41(21): 4066-4071, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-28929697

RESUMO

This study aims to analyze the effect of berberine on serum inflammatory factors and carotid atherosclerotic plaques in ppatients with acute cerebral ischemic stroke(AIS). In the study, 120 patients with AIS were randomly divided into berberine group(n=60) and general group (n=60). The 60 cases in the general group were provided with general therapy according to the latest guidelines of diagnosis and treatment of AIS. The berberine group received berberine 300 mg(tid) in addition to the therapy of the general group. The levels of serum inflammatory factors, the nerve function defect grades and the indexes of carotid atherosclerosis plaques [including the total plaque area(TPA), intima-media thickness(IMT) and the number of unstable carotid atherosclerotic plaques] were measured and compared. The results indicated that the levels of serum inflammatory factors, the NIHSS(national institute of health stroke scales) cores and the indexes of carotid atherosclerosis plaques were not significantly different between the berberine groups of general group, with positive correlation between serum inflammatory factors and NIHSS scores(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine groups on 14 d were significantly lower than those on 1 d(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine group on 14 d were significantly lower than those of the general group(P<0.05). The TPA and the number of unstable carotid atherosclerotic plaques of the berberine groups on 90 d were significantly lower than those of general group, with significant differences(P<0.05). The IMT showed a downward trend, but with significant difference.The mRS(modified rankin scale) scores of the berberine group on 90 d were significantly lower, with a higher rate of short-term favorable prognosis (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. This study showed that berberine in addition to the general therapy can significantly lower the levels of serum MIF and IL-6, reduce the degree of carotid atherosclerosis to some extent and improve neurological impairment and the prognosis of patients with AIS.


Assuntos
Anti-Inflamatórios/uso terapêutico , Berberina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Placa Aterosclerótica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Espessura Intima-Media Carotídea , Humanos , Interleucina-6/sangue , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Fatores de Risco
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