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1.
Cell Signal ; 121: 111256, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878804

RESUMO

The term ferroptosis, coined in 2012, has been widely applied in various disease research fields. Ferroptosis is a newly regulated form of cell death distinct from apoptosis, necrosis, and autophagy, the mechanisms of which have been extensively studied. Chronic kidney disease, characterized by renal dysfunction, is a common disease severely affecting human health, with its occurrence and development influenced by multiple factors and leading to dysfunction in multiple systems. It often lacks obvious clinical symptoms in the early stages, and thus, diagnosis is typically made in the later stages, complicating treatment. While research on ferroptosis and acute kidney injury has made continuous progress, studies on the association between ferroptosis and chronic kidney disease remain limited. This review aims to summarize chronic kidney disease, investigate the mechanism and regulation of ferroptosis, and attempt to elucidate the role of ferroptosis in the occurrence and development of chronic kidney disease.

2.
PLoS One ; 19(4): e0302419, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38687722

RESUMO

Workpiece surface defect detection is an indispensable part of intelligent production. The surface information obtained by traditional 2D image detection has some limitations due to the influence of environmental light factors and part complexity. However, the digital twin model has the characteristics of high fidelity and scalability, and the digital twin surface can be obtained by a device with a scanning accuracy of 0.02mm to achieve the representation of the real surface of the workpiece. The surface defect detection system for digital twin models is proposed based on the improved YOLOv5 model in this paper. Firstly, the digital twin model of the workpiece is reconstructed by the point cloud data obtained by the scanning device, and the surface features with defects are captured. Subsequently, the training dataset is calibrated based on the defect surface, where the defect types include Inclusion, Perforation, pitting surface and Rolled-in scale. Finally, the improved YOLOv5 model with CBAM mechanism and BiFPN module was used to identify the surface defects of the digital twin model and compare it with the original YOLOv5 model and other common models. The results show that the improved YOLOv5 model can realize the identification and classification of surface defects. Compared with the original YOLOv5 model, the mAP value of the improved YOLOv5 model has increased by 0.2%, and the model has high precision. On the basis of the same data set, the improved YOLOv5 model has higher recognition accuracy than other models, improving 11.7%, 3.4%, 6.2%, 33.5%, respectively. As a result, this study provides a practical and systematic detection method for digital twin model surface during the intelligent production process, and realizes the rapid screening of the workpiece with defects.


Assuntos
Propriedades de Superfície , Processamento de Imagem Assistida por Computador/métodos , Humanos , Modelos Teóricos , Algoritmos
3.
Neuropediatrics ; 54(4): 260-265, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36634691

RESUMO

BACKGROUND: Previous studies proved that the brain-derived neurotrophic factor (BDNF) is correlated with sleep regulation, yet how BDNF functions and reacts in the melatonin treatment of circadian rhythm sleep-wake disorder (CRSWD) among obese children remain enigmatic. Focusing on CRSWD in obese children, this study monitored their sleep efficiency and serum BDNF level changes during the treatment of melatonin. METHODS: In total, 35 obese children diagnosed with CRSWD were included in this study and administrated melatonin (3 mg/night) for 3 months. Blood samples were collected 24 hours before and after the treatment (08:00, 12:00, 16:00, 20:00, 24:00, and 04:00). Subsequently, the plasma melatonin level and serum BDNF level were measured by enzyme-linked immunosorbent assay. Sleep parameters, including sleep quality, Pittsburgh Sleep Quality Index as well as melatonin and BDNF levels before and after treatment, were recorded to profile the effectiveness and safety of melatonin treatment. RESULTS: Melatonin treatment increased plasma melatonin concentration and restored circadian rhythm. Besides, the serum BDNF level showed a significant increase, representing a strong positive correlation with melatonin concentration (p = 0.026). Patients experienced much-improved sleep efficiency (P < 0.001), with longer actual sleep time (P < 0.001), shorter sleep onset latency, and fewer awakenings after treatment (P < 0.001). Besides, melatonin was well tolerated by patients without producing severe side effects. CONCLUSION: Melatonin treatment effectively improved CRSWD among obese children with their serum BDNF levels increased, indicating that BDNF is a key regulator in CRSWD in obese children. This study may offer theoretical support for melatonin treatment of CRSWD in obese children.


Assuntos
Melatonina , Obesidade Infantil , Transtornos do Sono do Ritmo Circadiano , Transtornos do Sono-Vigília , Humanos , Criança , Melatonina/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/uso terapêutico , Obesidade Infantil/tratamento farmacológico , Transtornos do Sono do Ritmo Circadiano/tratamento farmacológico , Transtornos do Sono do Ritmo Circadiano/etiologia , Transtornos do Sono do Ritmo Circadiano/diagnóstico , Sono/fisiologia , Ritmo Circadiano/fisiologia
4.
J Sci Food Agric ; 102(2): 757-763, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34216009

RESUMO

BACKGROUND: Calcium pectinate (CaP) gel is traditionally prepared by de-esterifying high methoxyl pectin (HMP) to low methoxyl pectin (LMP), followed by gelation with calcium. To save both time and cost in the production of CaP gel, an alternative method was developed by the addition of CaCl2 to HMP at alkaline pH. To optimize the production, response surface methodology (RSM) was used to investigate the effects of temperature (30-50 °C), time (20-40 min) and pH (8-10) on yield, calcium content of the CaP gel and the degree of esterification (DE) of pectin following decalcification of CaP (DC-pectin). RESULTS: The linear term for pH had a significant effect (P < 0.01) on all three responses, whereas interaction effects were not significant (P > 0.01), except on the calcium content (P < 0.01). The optimized process conditions (temperature, time and pH) to obtain maximum CaP-HMP gel yield (88.83%) were 50 °C, 40 min and pH 9.6, and for the highest calcium content (97.23 mg g-1 ) they were 40 °C, 30 min and pH 9.7. DC-pectin was a typical LMP with DE varying from 26.92% to 50.33%. The DE of DC-pectin could be predicted by a model that proved significant (R2  = 0.9888). CONCLUSION: The optimum conditions were established to produce CaP gels from HMP with high yield and calcium content. Also, LMP with predictable DE can be produced following a significant model. This study provides new insights into the production and application of CaP gel. © 2021 Society of Chemical Industry.


Assuntos
Cálcio/química , Pectinas/química , Esterificação , Géis/química , Concentração de Íons de Hidrogênio , Temperatura , Viscosidade
5.
Foods ; 9(2)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32053983

RESUMO

Macadamia has increasing commercial importance in the food, cosmetics, and pharmaceutical industries. However, the toxic compound hydrogen cyanide (HCN) released from the hydrolysis of cyanogenic compounds in Macadamia causes a safety risk. In this study, optimum conditions for the maximum release of HCN from Macadamia were evaluated. Direct headspace analysis of HCN above Macadamia plant parts (flower, leaves, nuts, and husks) was carried out using selected ion flow tube-mass spectrometry (SIFT-MS). The cyanogenic glycoside dhurrin and total cyanide in the extracts were analyzed using HPLC-MS and UV-vis spectrophotometer, respectively. HCN released in the headspace was at a maximum when Macadamia samples were treated with pH 7 buffer solution and heated at 50 °C for 60 min. Correspondingly, treatment of Macadamia samples under these conditions resulted in 93%-100% removal of dhurrin and 81%-91% removal of total cyanide in the sample extracts. Hydrolysis of cyanogenic glucosides followed a first-order reaction with respect to HCN production where cyanogenesis is principally induced by pH changes initiating enzymatic hydrolysis rather than thermally induced reactions. The effective processing of different Macadamia plant parts is important and beneficial for the safe production and utilization of Macadamia-based products.

6.
Water Sci Technol ; 80(7): 1347-1356, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31850886

RESUMO

Polysilicate titanium salt (PST) is synthesized by using spent titanium solutions and polysilicic acid (PSiA) as raw materials. PSiA could improve the aggregation ability of titanium salt flocculants and also restrain the hydrolysis of Ti4+ to stabilize titanium salts. Meanwhile, replacing titanium salt with spent titanium solutions could reduce the cost of PST and solve the problem of wastewater treatment in the titanium industry, which makes valuable waste regeneration possible. Scanning electron microscopy (SEM) results show the morphology transformation (sheet, spheroid, and sphere) of PST with different Ti/Si molar ratios. The formation process of PST is analyzed by Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). This study investigates the effect of Ti/Si molar ratios on PST flocculation performance in humic-kaolin water and actual domestic wastewater treatment. The in situ floc size change of PST is measured by laser particle size analyzer in humic-kaolin water treatment. Additionally, the performance of PST is comprehensively evaluated on flocculation and sedimentation ability, rapid sweep netting ability and stability. In short, the prepared PST in this study is suitable for treating wastewater with high turbidity and chemical oxygen demand (COD) in a wide range of pH values.


Assuntos
Titânio , Purificação da Água , Floculação , Espectroscopia de Infravermelho com Transformada de Fourier , Águas Residuárias
7.
J Food Biochem ; 43(4): e12795, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31353605

RESUMO

Alliin is a natural organosulfur-containing phytochemical in garlic. It is possible that alliin can regulate the gut microbiota for its strong antimicrobial activity against many pathogens. Here, we assessed whether alliin impacts the distal small intestinal bacteria, hence the cecal microbiota, thus altering the gene expression of colonic epithelial tissues (CETs). Eighty mg/kg alliin was orally administered to rats for 14 days, and the 16S rDNA from small intestinal and cecal microbiota as well as mRNA from CETs were sequenced and analyzed. The results showed that alliin consumption affected microbiota composition in both the small intestine and cecum, although there was only one specific genus, Allobaculum that was significantly altered in the rat cecum. The altered composition of microbiota indirectly impacted 174 genes in the CETs. Specifically, five genes, including RT1-Ba, RT1-Bb, Cd80, Madcam1, and Aicda, indicated this consumption related to the intestinal immune network for IgA production. PRACTICAL APPLICATIONS: We firstly reported alliin consumption in vivo potentially affected the intestinal immunity of healthy rats by slightly alteration of microbiota composition in small intestine and cecum. The alteration subsequently amplified, resulting in the change of the colonic epithelial expression of several genes related to the intestinal immune network for IgA production. Hence, we suggested the alliin consumption may potentially affect the immune system of healthy individuals by alteration of gut microbiota and epithelial gene expression.


Assuntos
Ceco/metabolismo , Colo/microbiologia , Cisteína/análogos & derivados , Células Epiteliais/metabolismo , Alho/metabolismo , Microbioma Gastrointestinal , Intestino Delgado/metabolismo , Proteínas/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Ceco/microbiologia , Colo/metabolismo , Cisteína/metabolismo , Células Epiteliais/microbiologia , Alho/química , Expressão Gênica , Intestino Delgado/microbiologia , Proteínas/genética , Ratos , Ratos Sprague-Dawley
8.
J Thorac Dis ; 10(9): 5328-5338, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30416780

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) is reportedly overexpressed in most esophageal tumors, but most targeted therapies showed no efficacy in non-selected patients. This study aims at investigating the adaptive cetuximab subset in a cohort of esophageal squamous cell carcinoma (ESCC) patient-derived xenografts (PDXs). METHODS: A large panel of ESCC PDXs has been established. The copy number, mRNA expression and immunohistochemistry (IHC) of key EGFR pathways have been examined along with cetuximab response. A preclinical trial on a randomly selected cohort of 16 ESCC PDXs was conducted, and the genomic annotations of these models were compared against the efficacy readout of the mouse trial. RESULTS: The trial identified that 7 of 16 (43.8%) responded to cetuximab (ΔT/ΔC <0 as responders). The gene amplification and expression analysis indicated that EGFR copy number ≥5 (P=0.035), high EGFR mRNA expression (P=0.001) and IHC score of 2-3 (P=0.034) are associated with tumor growth inhibition by cetuximab, suggesting EGFR may function as a single predictive biomarker for cetuximab response in ESCC. CONCLUSIONS: Overall, our results suggest that an ESCC subtype with EGFR amplification and overexpression benefits from cetuximab treatment, which warrants further clinical confirmation.

9.
Mar Drugs ; 15(12)2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29236064

RESUMO

Marine algae have attracted a great deal of interest as excellent sources of nutrients. Polysaccharides are the main components in marine algae, hence a great deal of attention has been directed at isolation and characterization of marine algae polysaccharides because of their numerous health benefits. In this review, extraction and purification approaches and chemico-physical properties of marine algae polysaccharides (MAPs) are summarized. The biological activities, which include immunomodulatory, antitumor, antiviral, antioxidant, and hypolipidemic, are also discussed. Additionally, structure-function relationships are analyzed and summarized. MAPs' biological activities are closely correlated with their monosaccharide composition, molecular weights, linkage types, and chain conformation. In order to promote further exploitation and utilization of polysaccharides from marine algae for functional food and pharmaceutical areas, high efficiency, and low-cost polysaccharide extraction and purification methods, quality control, structure-function activity relationships, and specific mechanisms of MAPs activation need to be extensively investigated.


Assuntos
Alimento Funcional , Polissacarídeos/farmacologia , Alga Marinha/química , Relação Estrutura-Atividade , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Antivirais/química , Antivirais/farmacologia , Carboidratos da Dieta/farmacologia , Humanos , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Peso Molecular , Monossacarídeos/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação
10.
Food Chem ; 223: 25-30, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28069119

RESUMO

To investigate thermolysis kinetics and identify degradation compounds, alliin solutions were heated at 60, 80, and 89°C. The degradation compounds of alliin were identified by high performance liquid chromatography-mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS) and ultra-pressure liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). The results showed that the thermal degradation kinetic of alliin could be described by a first-order reaction and k=4.38×1017exp (-142494/RT), where k is the reaction rate constant, min-1; R is gas constant; T is the absolute temperature, K. Degraded compounds, including S-allyl-l-cysteine and ethers, such as allyl alanine disulfide, allyl alanine trisulfide, allyl alanine tetrasulfide, dialanine disulfide (cysteine), dialanine trisulfide and dialanine tetrasulfide, were identified by HPLC-MS, MS/MS and UPLC-HRMS. Allyl alanine tetrasulfide was identified for the first time in alliin. The results show that alliin is unstable and significant numbers of organosulfur compounds are generated under high temperature treatment.


Assuntos
Cisteína/análogos & derivados , Temperatura Alta , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Cisteína/análise , Cisteína/farmacocinética , Temperatura Alta/efeitos adversos , Cinética , Espectrometria de Massas em Tandem/métodos
11.
Oncotarget ; 7(31): 50575-50581, 2016 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-27409671

RESUMO

Cetuximab is an approved treatment for metastatic colorectal carcinoma (mCRC) with codon 12/13-KRAS mutations, recently questioned for its validity, and alternative mutation-based biomarkers were proposed. We set out to investigate whether an expression signature can also predict response by utilizing a cetuximab mouse clinical trial (MCT) dataset on a cohort of 25 randomly selected EGFR+ CRC patient-derived xenografts (PDXs). While we found that the expression of EGFR and its ligands are not predictive of the cetuximab response, we tested a published RAS pathway signature, a 147-gene expression signature proposed to describe RAS pathway activity, against this MCT dataset. Interestingly, our study showed that the observed cetuximab activity has a strong correlation with the RAS pathway signature score, which was also demonstrated to have a certain degree of correlation with a historic clinical dataset. Altogether, the independent validations in unrelated datasets from independent cohort of CRCs strongly suggest that RAS pathway signature may be a relevant expression signature predictive of CRC response to cetuximab. Our data seem to suggest that an mRNA expressing signature may also be developed as a predictive biomarker for drug response, similarly to genetic mutations.


Assuntos
Cetuximab/farmacologia , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas ras/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB/metabolismo , Perfilação da Expressão Gênica , Humanos , Ligantes , Camundongos , Mutação , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos
12.
J Agric Food Chem ; 64(16): 3206-14, 2016 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-27054263

RESUMO

A novel water-soluble polysaccharide-protein complex (PRW1) isolated from the sclerotia of an edible mushroom Polyporus rhinocerus which was purified by membrane ultrafiltration could significantly activate murine macrophages RAW264.7 in vitro. PRW1 had a molecular weight of less than 50 kDa and was found to be a highly branched heteropolysaccharide-protein complex composed of 45.7 ± 0.97% polysaccharide and 44.2 ± 0.41% protein. Based on the results of total acid hydrolysis, methylation analysis, and Fourier transform infrared spectroscopy, the carbohydrate moiety of PRW1 was found to be a ß-d-mannoglucan with its backbone containing →1)-d-Glcp-(4→, →1)-d-Glcp-(6→, and →1)-d-Manp-(2→ residues (molar ratio of 5:4:6) and having terminal d-Glcp as side chain (degree of branching of 0.62). In vitro studies showed that PRW1 significantly induced NO production and enhanced the release of a variety of cytokines including G-CSF, GM-CSF, IL-6, IL12p40/70, MCP-1, MCP-5, MIP-1-α, MIP-2, RANTES, sTNFRI, and TNF-α. Mechanistically, PRW1 treatment triggered ERK phosphorylation to activate macrophages within 15 min and significantly increased the expression level of inducible NOS after 6 h. In summary, this study indicates that PRW1 derived from the sclerotia of P. rhinocerus is a potential immunomodulatory agent for cancer immunotherapy.


Assuntos
Adjuvantes Imunológicos/farmacologia , Proteínas Fúngicas/farmacologia , Macrófagos/efeitos dos fármacos , Polyporus/química , Polissacarídeos/farmacologia , Animais , Western Blotting , Linhagem Celular , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel de Poliacrilamida , Proteínas Fúngicas/química , Macrófagos/imunologia , Camundongos , Polissacarídeos/química , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Cancer Biomark ; 16(4): 633-9, 2016 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-27002766

RESUMO

OBJECTIVE: To evaluate the expression of PARP1 in chordoma and analyzed its association with clinical factors and patients' prognosis. METHODS: The expression of Poly (ADP-ribose) polymerase 1 (PARP1) in chordoma specimens from 74 chordoma patients (50 primary and 24 recurrent tumors of 50 patients)and 20 distant normal tissue specimens was measured by immunohistochemical staining. The association of PARP1with the clinical factors and patients' prognosis was also analyzed. RESULTS: Of all the chordoma samples, 78% showed high expression of PARP1, whereas, only 10% of distant normal tissues expressed a high level of PARP1 (p< 0.01). Chi-square analysis revealed that high expression of PARP1 was significantly correlated with tumor recurrence (p< 0.01) and invasion into surrounding muscle (p< 0.01), while the data did not indicate any association with patients' gender, age, tumor location and size (p> 0.05). Kaplan-Meier survival curve and log-rank test showed that continuous disease free survival time (CDFS) was significantly shorter in the PARP1-positive group than in the PARP1-negative group (P= 0.019). CONCLUSION: High expression of PARP1 is significantly associated with chordoma invasion and recurrence. PARP1 may become a potential biomarker for chordoma in predicting its recurrence and patients' prognosis.


Assuntos
Biomarcadores Tumorais , Cordoma/metabolismo , Cordoma/mortalidade , Poli(ADP-Ribose) Polimerase-1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Cordoma/diagnóstico , Cordoma/genética , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Poli(ADP-Ribose) Polimerase-1/genética , Prognóstico , Carga Tumoral , Adulto Jovem
14.
Oncotarget ; 6(38): 40815-21, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26512781

RESUMO

Cetuximab is a standard of care for treating EGFR-expressing metastatic colorectal carcinoma (mCRC) exclusive of those with KRAS mutations at codons 12/13. However, retrospective analysis has recently suggested that KRAS-G13D patients can still benefit, while only a fraction of KRAS wild-type patients can benefit, from the treatment. We set out to test this contradicting issue experimentally in an independent cohort of patient derived xenograft (PDX) diseases. We conducted a mouse clinical trial (MCT) enrolling a random cohort of 27 transcriptome sequenced CRC-PDXs to evaluate cetuximab activity. The treatment responses were analyzed against the KRAS 12/13 mutation alleles, as well as several other well-known oncogenic alleles. If the response is defined by >80% tumor growth inhibition, 8/27 PDXs (~30%) are responders versus 19/27 non-/partial responders (~70%). We found that indeed there are no significantly fewer KRAS-12/13-allele responders (4/8 or 50%) than non-/partial responders (7/19, or 37%). In particular, there are actually no fewer G13D responders (4/8, or 50%) than in non-/partial responders (2/19 or 10.5%) statistically. Furthermore, majority of the non-/partial responders tend to have certain activating oncogenic alleles (one or more of the following common ones: K/N-RAS-G12V/D, -A146T, -Q61H/R, BRAF-V600E, AKT1-L52R and PIK3CA-E545G/K). Our data on an independent cohort support the recent clinical observation, but against the current practiced patient stratification in the cetuximab CRC treatment. Meanwhile, our data seem to suggest that a set of the six-oncogenic alleles may be of better predictive value than the current practiced stratification, justifying a new prospective clinical investigation on an independent cohort for confirmation.


Assuntos
Biomarcadores Tumorais/genética , Cetuximab/uso terapêutico , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Mutação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas/genética , Alelos , Animais , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Camundongos , Estudos Retrospectivos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Appl Microbiol Biotechnol ; 99(17): 7035-45, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25981997

RESUMO

Long-term stable cell growth and production of vindoline, catharanthine, and ajmalicine of cambial meristematic cells (CMCs) from Catharanthus roseus were observed after 2 years of culture. C. roseus CMCs were treated with ß-cyclodextrin (ß-CD) and methyl jasmonate (MeJA) individually or in combination and were cultured both in conventional Erlenmeyer flasks (100, 250, and 500 mL) and in a 5-L stirred hybrid airlift bioreactor. CMCs of C. roseus cultured in the bioreactor showed higher yields of vindoline, catharanthine, and ajmalicine than those cultured in flasks. CMCs of C. roseus cultured in the bioreactor and treated with 10 mM ß-CD and 150 µM MeJA gave the highest yields of vindoline (7.45 mg/L), catharanthine (1.76 mg/L), and ajmalicine (58.98 mg/L), concentrations that were 799, 654, and 426 % higher, respectively, than yields of CMCs cultured in 100-mL flasks without elicitors. Quantitative reverse transcription (RT)-PCR showed that ß-CD and MeJA upregulated transcription levels of genes related to the biosynthesis of terpenoid indole alkaloids (TIAs). This is the first study to report that ß-CD induced the generation of NO, which plays an important role in mediating the production of TIAs in C. roseus CMCs. These results suggest that ß-CD and MeJA can enhance the production of TIAs in CMCs of C. roseus, and thus, CMCs of C. roseus have significant potential to be an industrial platform for production of bioactive alkaloids.


Assuntos
Acetatos/metabolismo , Catharanthus/efeitos dos fármacos , Catharanthus/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Alcaloides de Triptamina e Secologanina/metabolismo , Vimblastina/análogos & derivados , Alcaloides de Vinca/metabolismo , beta-Ciclodextrinas/metabolismo , Células Cultivadas , Células Vegetais/efeitos dos fármacos , Células Vegetais/metabolismo , Vimblastina/metabolismo
16.
J Agric Food Chem ; 63(3): 787-94, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25579175

RESUMO

Garlic (Allium sativum L.), which is a widely distributed plant, is globally used as both spice and food. This study identified five novel phenolic compounds, namely, 8-(3-methyl-(E)-1-butenyl)diosmetin, 8-(3-methyl-(E)-1-butenyl)chrysin, 6-(3-methyl-(E)-1-butenyl)chrysin, and Alliumones A and B, along with nine known compounds 6-14 from the ethanol extract of garlic. The structures of these five novel phenolic compounds were established via extensive 1D- and 2D-nuclear magnetic resonance spectroscopy experiments. The effects of the phenolic compounds isolated from garlic on the enzymatical or nonenzymatical formation of sulfur-containing compounds produced during garlic processing were examined. Compound 12 significantly reduced the thermal decomposition of alliin, whereas compound 4 exhibited the highest percentage of alliinase inhibition activity (36.6%).


Assuntos
Manipulação de Alimentos , Alho/química , Fenóis/farmacologia , Compostos de Enxofre/antagonistas & inibidores , Compostos Orgânicos Voláteis/antagonistas & inibidores , Liases de Carbono-Enxofre/antagonistas & inibidores , Cisteína/análogos & derivados , Cisteína/química , Temperatura Alta , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fenóis/análise , Fenóis/química , Extratos Vegetais/química , Compostos de Enxofre/análise , Compostos Orgânicos Voláteis/química
17.
Nat Commun ; 5: 5567, 2014 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-25429397

RESUMO

Despite implications for carcinogenesis and other chronic diseases, basic mechanisms of p53 and its variants in suppressing Bcl-2 levels are poorly understood. Bcl-2 sustains mucous cell metaplasia, whereas p53(-/-) mice display chronically increased mucous cells. Here we show that p53 decreases bcl-2 mRNA half-life by interacting with the 5' untranslated region (UTR). The p53-bcl-2 mRNA interaction is modified by the substitution of proline by arginine within the p53 proline-rich domain (PRD). Accordingly, more mucous cells are present in primary human airway cultures with p53(Arg) compared with p53(Pro). Also, the p53(Arg) compared with p53(Pro) displays higher affinity to and activates the promoter region of SAM-pointed domain-containing Ets-like factor (SPDEF), a driver of mucous differentiation. On two genetic backgrounds, mice with targeted replacement of prolines in p53 PRD show enhanced expression of SPDEF and Bcl-2 and mucous cell metaplasia. Together, these studies define the PRD of p53 as a determinant for chronic mucous hypersecretion.


Assuntos
Genes p53/genética , Células Caliciformes/metabolismo , Pulmão/metabolismo , Mucinas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , RNA Mensageiro/metabolismo , Fumar/genética , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Fenótipo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fumar/metabolismo
18.
J Agric Food Chem ; 62(27): 6354-61, 2014 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-24916205

RESUMO

Calcium pectinate (CaP) was prepared from citrus pectin using either calcium chloride (C-CaP) or calcium hydroxide (HO-CaP) as the source of calcium for the reaction. The production yields and the rates of decalcification for the two calcium pectinates were compared and both found to be lower for C-CaP than for HO-CaP. In an attempt to explain these differences, certain chemical and structural characteristics of the two products, including functional groups (-CH3, C═O, COO-), rheological properties, morphology, and egg-box junction zones, were investigated by Fourier transformation infrared (FTIR) spectroscopy, rheology, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results from FTIR showed that, with an increase in calcium content, the wavenumber values and peak areas of FTIR for -CH3, C═O, and COO- groups all changed dramatically for C-CaP, while they were virtually unchanged for HO-CaP. Rheological analysis of the CaP gel showed that C-CaP had a stronger cross-linked network structure and a greater range of elastic behavior as compared to HO-CaP. SEM images of two CaP gels showed irregular membranes. C-CaP maintained a tight structure and a smooth surface, whereas HO-CaP was loose and rough. The results from XRD revealed a higher degree of crystallinity within C-CaP than within HO-CaP, which indicated that C-CaP possessed compact, ordered, and stable egg-box junction zones while the junction zones in HO-CaP were metastable and loose.


Assuntos
Citrus/química , Pectinas/química , Extratos Vegetais/química , Cloreto de Cálcio/química , Hidróxido de Cálcio/química , Estrutura Molecular , Pectinas/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Reologia , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
19.
Sci Rep ; 3: 2992, 2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-24141978

RESUMO

A preclinical trial identified 4 of 20 (20%) gastric cancer (GC) patient-derived xenografts responded to cetuximab. Genome-wide profiling and additional investigations revealed that high EGFR mRNA expression and immunohistochemistry score (3+) are associated with tumor growth inhibition. Furthermore, EGFR amplification were observed in 2/4 (50%) responders with average copy number 5.8 and >15 respectively. Our data suggest that a GC subtype with EGFR amplification and overexpression benefit from cetuximab treatment.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Receptores ErbB/genética , Amplificação de Genes , Expressão Gênica , Neoplasias Gástricas/genética , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Cetuximab , Modelos Animais de Doenças , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Mutação , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Carbohydr Polym ; 92(1): 200-5, 2013 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-23218283

RESUMO

The fructose polymer fructan was extracted from white garlic and fractionated using DEAE cellulose 52 and Sephadex G-100 columns to characterize its chemical composition and protective effect against ultraviolet radiation b (UVB) induced human keratinocyte (HaTaC) damage. Gel permeation chromatography, high performance anion exchange chromatography, infrared spectroscopy and 1D and 2D nuclear magnetic resonance spectroscopy were used to determine the chemical composition and functional characteristics of the garlic fructan (GF). GF was a homogeneous polysaccharide with a molecular weight of 4.54 × 10(3)Da. It was a member of the 1-kestose family, and it was composed of fructose and glucose at a ratio of 14:1. The main chain of GF was composed of (2→1)-ß-D-fructopyranose linked to a terminal (2→1)-α-D-glucopyranose at the non-reducing end and a (2→6)-ß-D-fructopyranose branched chain. The degree of polymerization was 28. Preliminary tests described herein indicated that GF may be effective in protecting HaTaC from UVB-induced damage.


Assuntos
Frutanos , Alho/química , Protetores contra Radiação/farmacologia , Trissacarídeos/química , Linhagem Celular/efeitos dos fármacos , Linhagem Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Cromatografia , Frutanos/química , Frutanos/isolamento & purificação , Frutanos/farmacologia , Humanos , Queratinócitos/efeitos da radiação , Espectroscopia de Ressonância Magnética , Peso Molecular , Protetores contra Radiação/química
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