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1.
Sci Rep ; 12(1): 8241, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35581317

RESUMO

Nutritional benefits and organoleptic characteristics, including visual, textural, taste, and flavor, are the critical characteristics of economically important fruit. Ripening is a crucial phenomenon in the formation of these quality characteristics in fruits. Therefore, controlling the ripening phenomenon is extremely important not only to maximize the benefits of the fruit but also to avoid food losses caused by over-ripening. Tomato is an important model plant, especially for research on fruit ripening. The metachronous model of tomato ripening is presented in this report. This model predicts the postharvest ripening time of tomato fruit in terms of red color development based on the storage period. A modified sigmoid-type function model was used to develop the prediction model. The observations and analyses were conducted at different storage temperatures and in different tomato cultivars. The result exhibits that the integration of the proposed model and time lag was successfully showing the postharvest ripening time history of tomato fruit at the full range ripening process, from onset to fully ripe. This study provides critical information on postharvest quality control research and supply chain development in eliminating food loss and waste, which leads to the realization of sustainable development goals.


Assuntos
Solanum lycopersicum , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/metabolismo , Proteínas de Plantas/genética , Temperatura
2.
Data Brief ; 39: 107473, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34712751

RESUMO

This dataset includes two kinds of data (for inventory analysis in Table A1 to A13, and precondition of waste and recycle for plastic and cardboard in Table A14) for conducting life cycle assessment (LCA) of strawberry-package supply chain with considering food loss during transportation Inventory analysis includes input data for LCA analysis. The data in the inventory was referenced from the publication of Plastic Waste Management Institute Plastic Waste Management Institute, (2017) and calculated based on the damage area ratio measured in our co-submitted article (Sasaki et al., 2022). This data helps to reproduce the article (Sasaki et al., 2022) for inventory analysis and re-analyze the environmental impact through the life cycle of strawberry assessed in the co-submitted article. Data of waste (incineration and landfill) and recycle ratios for plastic was collected from the previous reports of the publication Basic Knowledge of Plastic Recycle 2021 (Plastic Waste Management Institute, 2021), and data of the ratios for cardboard was referenced from Transition of Collect Rate on Cardboard (Ministry of the Environment (MOE), 2016). Ratios in this data show Japan-specialized values and is useful for creating the inventory.

3.
Food Chem ; 364: 130381, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34157592

RESUMO

The objective of this study was to explore the potentiality and mechanism of visible and near-infrared (Vis-NIR) spectroscopy in estimating the freshness of komatsuna. We monitored the cumulative CO2 production of komatsuna stored under different conditions as a freshness indicator and measured the Vis-NIR spectra of komatsuna as the predictor. Using the informative wavelengths (IW) selected using the stepwise selectivity ratio method, we constructed an accurate freshness prediction model through PLSR analysis. The IW in the visible region were attributed to pigments such as chlorophyll. In the NIR region, ten amino acids were identified as directly or indirectly contributing to the IW and were highly related to freshness. They were confirmed on the basis of the strong correlations between the informative NIR signals and NMR signals, which were determined using statistical heterospectroscopy. The results demonstrate the feasibility of Vis-NIR spectroscopy in estimating the freshness of komatsuna using the IW.


Assuntos
Metabolômica , Espectroscopia de Luz Próxima ao Infravermelho , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética
4.
PLoS One ; 16(4): e0249575, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33886595

RESUMO

The tomato (Solanum lycopersicum) ripening inhibitor (rin) mutation completely represses fruit ripening, as rin fruits fail to express ripening-associated genes and remain green and firm. Moreover, heterozygous rin fruits (rin/+) ripen normally but have extended shelf life, an important consideration for this perishable fruit crop; therefore, heterozygous rin has been widely used to breed varieties that produce red tomatoes with improved shelf life. We previously used CRISPR/Cas9 to produce novel alleles at the rin locus. The wild-type allele RIN encodes a MADS-box transcription factor and the novel allele, named as rinG2, generates an early stop codon, resulting in C-terminal truncation of the transcription factor. Like rin fruits, rinG2 fruits exhibit extended shelf life, but unlike rin fruits, which remain yellow-green even after long-term storage, rinG2 fruits turn orange due to ripening-associated carotenoid production. Here, to explore the potential of the rinG2 mutation for breeding, we characterized the effects of rinG2 in the heterozygous state (rinG2/+) compared to the effects of rin/+. The softening of rinG2/+ fruits was delayed compared to the wild type but to a lesser degree than rin/+ fruits. Lycopene and ß-carotene levels in rinG2/+ fruits were similar to those of the wild type, whereas rin/+ fruits accumulated half the amount of ß-carotene compared to the wild type. The rinG2/+ fruits produced lower levels of ethylene than wild-type and rin/+ fruits. Expression analysis revealed that in rinG2/+ fruits, the rinG2 mutation (like rin) partially inhibited the expression of ripening-associated genes. The small differences in the inhibitory effects of rinG2 vs. rin coincided with small differences in phenotypes, such as ethylene production, softening, and carotenoid accumulation. Therefore, rinG2 represents a promising genetic resource for developing tomato cultivars with extended shelf life.


Assuntos
Etilenos/metabolismo , Frutas/crescimento & desenvolvimento , Genes Dominantes , Proteínas de Domínio MADS/metabolismo , Mutação , Proteínas de Plantas/metabolismo , Solanum lycopersicum/crescimento & desenvolvimento , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Proteínas de Domínio MADS/genética , Fenótipo , Proteínas de Plantas/genética
5.
Res Rep Urol ; 12: 455-461, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117745

RESUMO

BACKGROUND: To evaluate the organ-specific therapeutic effect of paclitaxel and carboplatin (TC) chemotherapy in patients who failed platinum-based chemotherapy and pembrolizumab for metastatic urothelial carcinoma (UC). PATIENTS AND METHODS: We retrospectively reviewed the data of patients with metastatic UC who had received TC chemotherapy after the failure of platinum-based chemotherapy and pembrolizumab. The RECIST 1.1 criteria were used to assess the objective response to pembrolizumab and TC chemotherapy at tumor sites. RESULTS: We analyzed 8 patients (male, n=5; female, n=3; median age, 65 years old). All patients except one had visceral metastasis. The median overall survival for TC was 10.9 months (95% confidence interval, 1.0­12.7 months), and the objective response rate was 25.0% (partial response [PR]: 2 cases). The metastatic organs were the lymph nodes in 5 cases (number of tumor sites: 8), lung in 4 cases (number of tumor sites: 12), liver in 3 cases (number of tumor sites: 14), bone in 3 cases (number of tumor sites: 12), and primary lesion in 3 cases (number of tumor sites: 3). There were no cases of a complete response or progressive disease in any metastatic organs due to TC chemotherapy. A PR was seen in 2 cases of lymph node metastasis (40.0%), 2 cases of lung metastasis (50.0%), and 2 cases of liver metastasis (66.7%). All 3 cases of bone metastasis showed stable disease, as did all 3 cases of primary lesion. Improvement in the therapeutic effect of TC chemotherapy compared with pembrolizumab was observed in 2 cases (40.0%) of lymph node metastasis, 2 cases (50.0%) of lung metastasis, and 1 case (33.3%) of liver metastasis. CONCLUSION: Lymph node, lung, and liver metastases may respond to TC chemotherapy, even if exacerbated with pembrolizumab after platinum-based chemotherapy in metastatic UC.

6.
Int J Mol Sci ; 21(7)2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32283652

RESUMO

Glyceraldehyde-derived advanced glycation end products (glycer-AGEs) contribute to proximal tubulopathy in diabetes. However, what glycer-AGE structure could evoke tubular cell damage remains unknown. We first examined if deleterious effects of glycer-AGEs on reactive oxygen species (ROS) generation in proximal tubular cells were blocked by DNA-aptamer that could bind to glyceraldehyde-derived pyridinium (GLAP) (GLAP-aptamer), and then investigated whether and how GLAP caused proximal tubular cell injury. GLAP-aptamer and AGE-aptamer raised against glycer-AGEs were prepared using a systemic evolution of ligands by exponential enrichment. The binding affinity of GLAP-aptamer to glycer-AGEs was measured with a bio-layer interferometry. ROS generation was evaluated using fluorescent probes. Gene expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). GLAP-aptamer bound to glycer-AGEs with a dissociation constant of 7.7 × 10-5 M. GLAP-aptamer, glycer-AGE-aptamer, or antibodies directed against receptor for glycer-AGEs (RAGE) completely prevented glycer-AGE- or GLAP-induced increase in ROS generation, MCP-1, PAI-1, or RAGE gene expression in tubular cells. Our present results suggest that GLAP is one of the structurally distinct glycer-AGEs, which may mediate oxidative stress and inflammatory reactions in glycer-AGE-exposed tubular cells. Blockade of the interaction of GLAP-RAGE by GLAP-aptamer may be a therapeutic target for proximal tubulopathy in diabetic nephropathy.


Assuntos
Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Gliceraldeído/farmacologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Compostos de Piridínio/farmacologia , Biomarcadores , Células Cultivadas , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Produtos Finais de Glicação Avançada/farmacologia , Gliceraldeído/análogos & derivados , Humanos , Túbulos Renais/patologia , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Estresse Oxidativo/efeitos dos fármacos , Compostos de Piridínio/química , Espécies Reativas de Oxigênio/metabolismo
7.
Plant Physiol ; 183(1): 80-95, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32094307

RESUMO

RIPENING INHIBITOR (RIN) is a transcription factor with transcriptional activator activity that plays a major role in regulating fruit ripening in tomato (Solanum lycopersicum). Recent studies have revealed that (1) RIN is indispensable for full ripening but not for the induction of ripening; and (2) the rin mutation, which produces nonripening fruits that never turn red or soften, is not a null mutation but instead converts the encoded transcriptional activator into a repressor. Here, we have uncovered aspects of RIN function by characterizing a series of allelic mutations within this locus that were produced by CRISPR/Cas9. Fruits of RIN-knockout plants, which are characterized by partial ripening and low levels of lycopene but never turn fully red, showed excess flesh softening compared to the wild type. The knockout mutant fruits also showed accelerated cell wall degradation, suggesting that, contrary to the conventional view, RIN represses over-ripening in addition to facilitating ripening. A C-terminal domain-truncated RIN protein, encoded by another allele of the RIN locus (rinG2), did not activate transcription but formed transcription factor complexes that bound to target genomic regions in a manner similar to that observed for wild-type RIN protein. Fruits expressing this truncated RIN protein exhibited extended shelf life, but unlike rin fruits, they accumulated lycopene and appeared orange. The diverse ripening properties of the RIN allelic mutants suggest that substantial phenotypic variation can be produced by tuning the activity of a transcription factor.


Assuntos
Frutas/genética , Frutas/fisiologia , Solanum lycopersicum/genética , Solanum lycopersicum/fisiologia , Alelos , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Solanum lycopersicum/metabolismo , Mutação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
8.
J Oncol ; 2019: 7387601, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565056

RESUMO

Accumulating evidence has suggested the pathological role of advanced glycation end products (AGEs) and their receptor RAGE axis in aging-associated disorders, including cancers. In this study, we examined the effects of local injection of RAGE-aptamer adjacent to the tumor on G361 melanoma growth in nude mice. We further investigated the effects of RAGE-aptamer on oxidative stress generation, RAGE, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) gene expression in N ε -(carboxymethyl)lysine (CML)-exposed G361 melanoma cells in vitro. Local injection of RAGE-aptamer adjacent to the tumor dramatically decreased the growth of G361 melanoma in nude mice, which was associated with reduced expression of CML, RAGE, nitrotyrosine, VEGF, CD31, and von Willebrand factor, markers of endothelial cells in G361 tumors. Furthermore, RAGE-aptamer inhibited the binding of CML to V-domain of RAGE and blocked the CML-induced increases in oxidative stress generation, RAGE, VEGF, and MCP-1 mRNA levels in G361 melanoma cells. Our present findings suggest that long-term local injection of RAGE-aptamer adjacent to the tumor could inhibit melanoma growth in nude mice partly by suppressing tumor angiogenesis via blockade of the CML-RAGE interaction. Local injection of RAGE-aptamer may be a feasible therapeutic tool for the treatment of malignant melanoma.

9.
Microvasc Res ; 120: 90-93, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30056058

RESUMO

We have previously shown that albuminuria and renal levels of advanced glycation end products (AGEs), receptor for AGEs (RAGE), and oxidative stress are suppressed in dipeptidyl peptidase-4 (DPP-4)-deficient diabetic rats, thus suggesting the crosstalk between AGE-RAGE axis and DPP-4 in experimental diabetic nephropathy. Therefore, we examined here the role of DPP-4 in AGE-evoked inflammatory reactions in human proximal tubular cells. Proteins were extracted from proximal tubular cells, and conditioned medium was collected, both of which were subjected to western blot analysis using anti-DPP-4 antibody. RAGE-aptamer was prepared using a systemic evolution of ligands by exponential enrichment. NF-κB p65 and monocyte chemoattractant protein-1 (MCP-1) gene expression was analyzed by reverse transcription-polymerase chain reaction. AGEs significantly increased DPP-4 expression and soluble DPP-4 production by tubular cells, the latter of which was attenuated by RAGE-aptamer or an anti-oxidant, N-acetylcysteine. AGEs or DPP-4 up-regulated NF-κB p65 or MCP-1 mRNA levels in tubular cells, which were suppressed by linagliptin, an inhibitor of DPP-4. AGEs stimulated NF-κB p65 gene expression in tubular cells isolated from control rats, but not from DPP-4-deficient rats. Our present results suggest that the AGE-RAGE-mediated oxidative stress could evoke inflammatory reactions in proximal tubular cells via autocrine production of DPP-4.


Assuntos
Comunicação Autócrina/efeitos dos fármacos , Dipeptidil Peptidase 4/metabolismo , Produtos Finais de Glicação Avançada/toxicidade , Mediadores da Inflamação/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Soroalbumina Bovina/toxicidade , Animais , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Dipeptidil Peptidase 4/deficiência , Dipeptidil Peptidase 4/genética , Humanos , Túbulos Renais Proximais/enzimologia , Túbulos Renais Proximais/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Ratos Transgênicos , Receptor para Produtos Finais de Glicação Avançada/agonistas , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo
10.
Ann Nucl Med ; 32(3): 217-235, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29333565

RESUMO

Here we present the guideline for the treatment of neuroendocrine tumors using Lu-177-DOTA-TATE on the basis of radiation safety aspects in Japan. This guideline was prepared by a study supported by Ministry of Health, Labour, and Welfare, and approved by Japanese Society of Nuclear Medicine. Lu-177-DOTA-TATE treatment in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection shown in this guideline are considered internationally useful as well. Only the original Japanese version is the formal document.


Assuntos
Lutécio/uso terapêutico , Tumores Neuroendócrinos/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Pessoal de Saúde/educação , Humanos , Japão , Lutécio/química , Manuais como Assunto , Medicina Nuclear/educação , Medicina Nuclear/legislação & jurisprudência , Medicina Nuclear/métodos , Guias de Prática Clínica como Assunto , Proteção Radiológica/métodos , Segurança
11.
Nat Plants ; 3(11): 866-874, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29085071

RESUMO

Tomato (Solanum lycopersicum) rin mutants completely fail to ripen: they do not produce red pigmentation, soften or induce an ethylene burst. Therefore, RIN has long been believed to function as a major regulator that is essential for the induction of ripening. Here, we provide evidence contradicting this concept of RIN function, showing induction of fruit ripening in the absence of RIN. A CRISPR/Cas9-mediated RIN-knockout mutation did not repress initiation of ripening and the mutant fruits showed moderate red colouring. Moreover, inactivation of the rin mutant allele partially restored the induction of ripening. Therefore, RIN is not required for the initiation of ripening and rin is not a null mutation, but rather is a gain-of-function mutation that produces a protein that actively represses ripening. Since the discovery of the rin mutant a half-century ago, many models have depicted RIN as indispensable for the induction of ripening; these models should be reconsidered in light of these results.


Assuntos
Frutas/crescimento & desenvolvimento , Genes de Plantas , Proteínas de Domínio MADS/fisiologia , Proteínas de Plantas/fisiologia , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/genética , Alelos , Frutas/genética , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Genes Recessivos , Proteínas de Domínio MADS/genética , Mutação , Proteínas de Plantas/genética , Regiões Promotoras Genéticas , Ligação Proteica
12.
Diab Vasc Dis Res ; 14(5): 450-453, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28631505

RESUMO

OBJECTIVE: Glyceraldehyde-derived advanced glycation end products contribute to vascular inflammation in diabetes. However, what advanced glycation end product structure could evoke inflammatory reactions remains unknown. We examined whether and how methylglyoxal-derived hydroimidazolone 1, one of the advanced glycation end products formed from glyceraldehyde, elicits inflammatory reactions in human umbilical vein endothelial cells. MATERIALS AND METHODS: Glyceraldehyde-advanced glycation end products-aptamer was prepared using a systemic evolution of ligands by exponential enrichment. The binding affinities of methylglyoxal-derived hydroimidazolone 1 to receptor for advanced glycation end products or advanced glycation end product-aptamer were measured with a quartz crystal microbalance. Intracellular reactive oxygen species generation and THP-1 cell adhesion were evaluated using fluorescent probes. Gene expression was analysed by reverse transcription polymerase chain reaction. RESULTS: Methylglyoxal-derived hydroimidazolone 1 bound to receptor for advanced glycation end products and advanced glycation end product-aptamer with a dissociation constant ( Kd) of 56.7 µM and 1.51 mM, respectively. Methylglyoxal-derived hydroimidazolone 1 at 100 µg/mL significantly increased reactive oxygen species generation in human umbilical vein endothelial cells, which were attenuated by anti-receptor for advanced glycation end products antibody or advanced glycation end product-aptamer. In all, 100 µg/mL methylglyoxal-derived hydroimidazolone 1 significantly increased receptor for advanced glycation end products and intercellular adhesion molecule-1 messenger RNA levels in, and THP-1 cell adhesion to, human umbilical vein endothelial cells, all of which were blocked by anti-receptor for advanced glycation end products antibody. CONCLUSION: Our present results indicate that methylglyoxal-derived hydroimidazolone 1 evokes inflammatory reactions in human umbilical vein endothelial cells via receptor for advanced glycation end products, although apparently limited to supraphysiological levels of methylglyoxal-derived hydroimidazolone 1. Methylglyoxal-derived hydroimidazolone 1 is a distinct advanced glycation end product structure that could mediate harmful effects of methylglyoxal and glyceraldehyde-mediated glycation processes.


Assuntos
Produtos Finais de Glicação Avançada/toxicidade , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Imidazóis/toxicidade , Mediadores da Inflamação/metabolismo , Inflamação/induzido quimicamente , Aldeído Pirúvico/toxicidade , Receptor para Produtos Finais de Glicação Avançada/agonistas , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Produtos Finais de Glicação Avançada/metabolismo , Células Endoteliais da Veia Umbilical Humana/imunologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Imidazóis/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Ligação Proteica , Aldeído Pirúvico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
13.
Diabetes ; 66(6): 1683-1695, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28385802

RESUMO

The interaction of advanced glycation end products (AGEs) and their receptor (RAGE) plays a central role in diabetic nephropathy. We screened DNA aptamers directed against RAGE (RAGE-aptamers) in vitro and examined the effects on the development and progression of diabetic nephropathy in streptozotocin-induced diabetic rats. RAGE-aptamer bound to RAGE with a Kd of 5.68 nmol/L and resultantly blocked the binding of AGEs to RAGE. When diabetic rats received continuous intraperitoneal injection of RAGE-aptamer from week 7 to 11 of diabetes, the increases in renal NADPH oxidase activity, oxidative stress generation, AGE, RAGE, inflammatory and fibrotic gene and protein levels, macrophage and extracellular matrix accumulation, and albuminuria were significantly suppressed, which were associated with improvement of podocyte damage. Two-week infusion of RAGE-aptamer just after the induction of diabetes also inhibited the AGE-RAGE-oxidative stress system and MCP-1 levels in the kidneys of 8-week-old diabetic rats and simultaneously ameliorated podocyte injury and albuminuria. Moreover, RAGE-aptamer significantly suppressed the AGE-induced oxidative stress generation and inflammatory and fibrotic reactions in human cultured mesangial cells. The findings suggest that continuous infusion of RAGE-aptamer could attenuate the development and progression of experimental diabetic nephropathy by blocking the AGE-RAGE axis.


Assuntos
Aptâmeros de Nucleotídeos/farmacologia , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Rim/efeitos dos fármacos , Células Mesangiais/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Albuminúria , Animais , Quimiocina CCL2/efeitos dos fármacos , Quimiocina CCL2/genética , Ensaio de Imunoadsorção Enzimática , Fibrose/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Inflamação/genética , Rim/metabolismo , Masculino , Células Mesangiais/patologia , NADPH Oxidases/efeitos dos fármacos , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Podócitos/efeitos dos fármacos , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Receptor para Produtos Finais de Glicação Avançada/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo
14.
Mol Med ; 23: 295-306, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29387865

RESUMO

Epidemiological studies have suggested the link between cumulative diabetic exposure and cancer. Interaction of advanced glycation end products (AGEs) with their receptor (RAGE) may contribute to the phenomenon. We examined here the effects of DNA aptamer raised against RAGE (RAGE-aptamer) on growth and liver metastasis of G361 melanoma in nude mice. Malignant melanoma cells were intradermally injected into the upper flank region of nude mice, which received continuous administration of RAGE-aptamer (38.4 pmol/day/g body weight) or vehicle intraperitoneally by an osmotic pump up to 42 days. RAGE-aptamer significantly reduced levels of 8-hydroxy-2'-deoxy-guanosine, AGEs, RAGE, proliferating nuclear antigen, cyclin D1, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), and CD31 and Mac-3, respective markers of endothelial cells and macrophages in tumors of nude mice and suppressed the proliferation and liver metastasis of malignant melanoma. Furthermore, RAGE-aptamer attenuated the AGE-induced oxidative stress generation, proliferation, and VEGF and MCP-1 gene expression in both G361 melanoma cells and endothelial cells. The present findings suggest that RAGE-aptamer could attenuate melanoma growth and liver metastasis in nude mice by suppressing the tumor angiogenesis and macrophage infiltration via inhibition of the AGE-RAGE system. RAGE-aptamer may be a novel therapeutic tool for the treatment of malignant melanoma.


Assuntos
Aptâmeros de Nucleotídeos/uso terapêutico , Neoplasias Hepáticas/prevenção & controle , Melanoma Experimental/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Receptor para Produtos Finais de Glicação Avançada , Animais , Linhagem Celular , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Neoplasias Hepáticas/secundário , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos Nus
15.
J Diabetes ; 9(2): 141-148, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27556881

RESUMO

Epidemiological studies have suggested that cumulative diabetic exposure, namely prolonged exposure to chronic hyperglycemia, contributes to the increased risk of cardiovascular disease (CVD) in diabetes. The formation and accumulation of advanced glycation end-products (AGEs) have been known to progress under hyperglycemic conditions. Because AGEs-modified collagens are hardly degraded and remain in diabetic vessels, kidneys and the heart for a long time, even after glycemic control has been achieved, AGEs could become a marker reflecting cumulative diabetic exposure. Furthermore, there is a growing body of evidence that an interaction between AGEs and the receptor for AGEs (RAGE) plays a role in the pathogenesis of CVD. In addition, AGEs induce the expression of RAGE, thus leading to sustained activation of the AGEs-RAGE axis in diabetes. Herein we review the pathological role of the AGEs-RAGE axis in CVD, focusing particularly on the phenomenon of metabolic memory, and discuss the potential clinical usefulness of measuring circulating and tissue levels of AGEs accumulation to evaluate diabetic macrovascular complications.


Assuntos
Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Diabetes Mellitus/sangue , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/metabolismo , Humanos , Ligação Proteica , Fatores de Risco
16.
Biocontrol Sci ; 20(4): 285-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26699860

RESUMO

An outbreak of Escherichia coli O157:H7 occurred due to the consumption of sweet dumplings in Japan. We examined the survival of E. coli O157:H7 inoculated into several types of sweet dumplings to evaluate the progress of the residual contaminating pathogens after the production or packing processes. For all 4 types of tested typical sweet dumplings, no significant reduction in the viable cell counts of inoculated E. coli O157:H7 (3 log CFU/g) was observed during storage at -20 ℃ and 5 ℃ for 5 weeks. Approximately 1 log CFU/g of reduction was observed after storage for 5 weeks at 10 ℃ and 15 ℃, which corresponded to the growth of the naturally contaminating fungi. Similar results were obtained when we used several types of commercially distributed sweet dumplings. It is of vital importance to prevent the cross contamination of sweet dumplings after the heating process in order to reduce the risk of foodborne illness.


Assuntos
Escherichia coli O157/isolamento & purificação , Escherichia coli O157/fisiologia , Microbiologia de Alimentos , Armazenamento de Alimentos , Viabilidade Microbiana , Contagem de Colônia Microbiana , Japão , Temperatura , Fatores de Tempo
17.
Mol Med ; 21 Suppl 1: S32-40, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26605646

RESUMO

A nonenzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and subsequently alters their structural integrity and function. This process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent and senescent macroprotein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence indicating that interaction of AGEs with their receptor (RAGE) elicits oxidative stress generation and as a result evokes proliferative, inflammatory, thrombotic and fibrotic reactions in a variety of cells. This evidence supports AGEs' involvement in diabetes- and aging-associated disorders such as diabetic vascular complications, cancer, Alzheimer's disease and osteoporosis. Therefore, inhibition of AGE formation could be a novel molecular target for organ protection in diabetes. This report summarizes the pathophysiological role of AGEs in vascular complications in diabetes and discusses the potential clinical utility of measurement of serum levels of AGEs for evaluating organ damage in diabetes.


Assuntos
Inibidores de Adenosina Desaminase/uso terapêutico , Aptâmeros de Nucleotídeos/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/complicações , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/patologia , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Expressão Gênica , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/genética , Osteoporose/patologia , Estresse Oxidativo , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo
18.
Diabetol Metab Syndr ; 7: 48, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26023321

RESUMO

BACKGROUND: Ninety percent of glucose filtered by the glomerulus is reabsorbed by a sodium-glucose cotransporter 2 (SGLT2), which is expressed mainly on the apical membrane of renal proximal tubules. Since SGLT-2-mediated glucose reabsorption is enhanced under diabetic conditions, selective inhibition of SGLT2 has been proposed as a potential therapeutic target for the treatment of patients with diabetes. However, it remains unclear which diabetes-associated factors are involved in overexpression of SGLT2. METHODS: Therefore, in this study, we examined whether insulin, high glucose, advanced glycation end products (AGEs), or H2O2 stimulated SGLT2 expression in human cultured proximal tubular cells, and then investigated the underlying molecular mechanisms. RESULTS: High glucose or AGEs did not affect SGLT2 expression in tubular cells. Insulin significantly increased tubular SGLT2 level in a dose-dependent manner, whereas bell-shaped dose-response curves were observed for H2O2-treated cells. An anti-oxidant, N-acetylcysteine completely blocked insulin-induced up-regulation of SGLT2 as well as increase in glucose absorption by tubular cells. Furthermore, insulin dose-dependently increased reactive oxygen species generation in tubular cells. CONCLUSIONS: Our present study demonstrated that insulin could stimulate SGLT-2-mediated glucose entry into cultured proximal tubular cells via oxidative stress generation. Suppression of the insulin-induced overexpression of SGLT2 in tubular cells might be a novel therapeutic strategy for the treatment of diabetic nephropathy.

19.
Food Microbiol ; 49: 226-30, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25846935

RESUMO

Contamination of spices by pathogenic and/or spoilage bacteria can be deleterious to consumer's health and cause deterioration of foods, and inactivation of such bacteria is necessary for the food industry. The present study examined the effect of gaseous acetic acid treatment in reducing Escherichia coli O157:H7, Salmonella Enteritidis and Bacillus subtilis populations inoculated on fenugreek seeds and black pepper. Treatment with gaseous acetic acid at 0.3 mmol/L, 0.6 mmol/L and 4.7 mmol/L for 1-3 h significantly reduced the populations of E. coli O157:H7 and Salmonella Enteritidis on black pepper and fenugreek seeds at 55 °C (p < 0.05). The gas treatments at 4.7 mmol/L were more effective in inactivating the pathogens than the treatment at 0.3 mmol/L. An approximately 5.0 log reduction was obtained after 3 h of treatment with 4.7 mmol/L acetic acid. No significant reductions in the population of B. subtilis spores inoculated on fenugreek seeds and black pepper were obtained after the gas treatments at 0.3 mmol/L or 0.6 mmol/L (p > 0.05). However, the gas treatment at 4.7 mmol/L significantly reduced B. subtilis spores (p < 0.05), and 4.0 log CFU/g and 3.5 log CFU/g reductions on fenugreek seeds and black pepper, respectively, were obtained after 3 h of treatment.


Assuntos
Ácido Acético/farmacologia , Desinfetantes/farmacologia , Desinfecção/métodos , Piper nigrum/microbiologia , Trigonella/microbiologia , Ácido Acético/química , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Desinfetantes/química , Escherichia coli O157/efeitos dos fármacos , Escherichia coli O157/crescimento & desenvolvimento , Gases/química , Gases/farmacologia , Salmonella enteritidis/efeitos dos fármacos , Salmonella enteritidis/crescimento & desenvolvimento , Sementes/microbiologia
20.
J Food Prot ; 78(4): 819-24, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25836411

RESUMO

Under osmotic stress, bacterial cells uptake compatible solutes such as glycine-betaine to maintain homeostasis. It is unknown whether incompatible solutes exist that are similar in structure to compatible solutes but have adverse physiological effects on bacterial physiology. The objective of this study was to evaluate solute incompatibility of various amino acids against bacterial growth. Bacterial growth was evaluated by changes in optical density at 595 nm in peptone-yeast-glucose (PYG) broth. Twenty-three amino acids with L and/or D isomers were examined for the effect of bacterial growth inhibition. Among the various amino acids examined, D-tryptophan (∼ 40 mM) in PYG broth supplemented with 0 to 4% (wt/vol) salt inhibited the growth of Listeria monocytogenes, Salmonella enterica, and Escherichia coli O157:H7 at 25 °C. D-Tryptophan (30 to 40 mM) completely inhibited the growth of E. coli O157:H7 and Salmonella in the presence of >3% salt, but the growth of L. monocytogenes was not completely inhibited under the same conditions. Low concentrations of salt (0 to 2% NaCl) with D-tryptophan did not significantly inhibit the growth of all bacteria except L. monocytogenes, which was relatively inhibited at 0% NaCl. The effect of D-tryptophan differed depending on the bacterial species, illustrating the difference between gram-positive and gram-negative bacteria. These results indicate that the uptake of D-tryptophan as a compatible solute during osmotic stress may inhibit bacterial growth. The antibacterial effect of D-tryptophan found in this study suggests that D-tryptophan could be used as a novel preservative for controlling bacterial growth in foods.


Assuntos
Escherichia coli O157/efeitos dos fármacos , Listeria monocytogenes/efeitos dos fármacos , Salmonella enterica/efeitos dos fármacos , Triptofano/farmacologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli O157/crescimento & desenvolvimento , Microbiologia de Alimentos , Conservantes de Alimentos , Listeria monocytogenes/crescimento & desenvolvimento , Pressão Osmótica , Salmonella enterica/crescimento & desenvolvimento , Soluções
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