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1.
Molecules ; 27(19)2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36235272

RESUMO

This study aimed to evaluate the antiglycation effects of adlay on protein glycation using in vitro glycation assays. Adlay seed was divided into the following four parts: the hull (AH), testa (AT), bran (AB), and polished adlay (PA). A solvent extraction technique and column chromatography were utilized to investigate the active fractions and components of adlay. Based on a BSA-glucose assay, the ethanolic extracts of AT (ATE) and AB (ABE) revealed a greater capacity to inhibit protein glycation. ATE was further consecutively partitioned into four solvent fractions with n-hexane, ethyl acetate (ATE-Ea), 1-butanol (ATE-BuOH), and water. ATE-BuOH and -Ea show marked inhibition of glucose-mediated glycation. Medium-high polarity subfractions eluted from ATE-BuOH below 50% methanol with Diaion HP-20, ATE-BuOH-c to -f, exhibited superior antiglycation activity, with a maximum inhibitory percentage of 88%. Two phenolic compounds, chlorogenic acid and ferulic acid, identified in ATE-BuOH with HPLC, exhibited potent inhibition of the individual stage of protein glycation and its subsequent crosslinking, as evaluated by the BSA-glucose assay, BS-methylglyoxal (MGO) assay, and G.K. peptide-ribose assay. In conclusion, this study demonstrated the antiglycation properties of ATE in vitro that suggest a beneficial effect in targeting hyperglycemia-mediated protein modification.


Assuntos
Coix , Polifenóis , 1-Butanol , Antioxidantes/farmacologia , Ácido Clorogênico/análise , Coix/química , Glucose/análise , Óxido de Magnésio , Metanol/análise , Extratos Vegetais/química , Polifenóis/análise , Polifenóis/farmacologia , Aldeído Pirúvico/análise , Ribose , Sementes/química , Solventes/análise , Água/análise
2.
Chin J Physiol ; 63(3): 137-148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32594067

RESUMO

Cajanus cajan (L.) Millsp., also named pigeon pea, is widely grown in the tropics and the subtropics. C. cajan roots (CR) and ribs stewed in hot water have been used as a traditional medicine in various cultures to treat diabetes. The purpose of this study was to determine the functional components of hot water (WCR) and 50%, 95% ethanol extracts (EECR50 and EECR95) from CR, then evaluating their antioxidant and anti-inflammatory effects. The results indicated that EECR95 had higher polyphenol, especially the isoflavones (e.x. daidzein, genistein, and cajanol) than those of the other extracts, and it also exhibited the most potent anti-oxidative activities by in vitro antioxidant assay. In the lipopolysaccharide-stimulated RAW 264.7 cells, we found that EECR95 significantly decreased intracellular reactive oxygen species and significantly enhanced the activities of superoxide dismutase and catalase. Mechanism studies showed that EECR95 mainly activated nuclear factor (NF) erythroid 2-related factor 2/antioxidant protein heme oxygenase-1 and inhibited nuclear factor kappa B (NF-κB) signaling pathway, and thus exhibited antioxidant and anti-inflammatory effects. Overall, this study suggests that CR may have the potential to be developed as a biomedical material and that genistein, which has relatively high uptakes (3.44% for the pure compound and 1.73% for endogenous genistein of EECR95) at 24 h of incubation with RAW 264.7 cells, could be the main active component of CR.


Assuntos
Cajanus , Anti-Inflamatórios , Antioxidantes , Extratos Vegetais , Espécies Reativas de Oxigênio
3.
Cell Physiol Biochem ; 49(5): 1970-1986, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30235439

RESUMO

BACKGROUND/AIMS: Uterine leiomyomas (ULs) are benign uterine tumors, and the most notable pathophysiologic feature of ULs is excessive accumulation of extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown seaweeds that has a wide range of pharmacological properties, including anti-fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs activated by transforming growth factor beta (TGFß). METHODS: We used ELT-3 (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle cells) as in vitro models. Cell viability was determined by the MTT assay. Cell colony formation was stained using crystal violet. The side population, cell cycle and apoptosis were analyzed using flow cytometry. Protein expression was assayed by western blot analysis. We also conducted in vivo experiments to confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor tissues were assayed by immunohistochemistry analysis. RESULTS: In our study, fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, α-SMA and the COL1A1 protein levels in TGFß3-induced ELT-3 cells. In the cellular mechanism, fucoidan abrogated TGFß3-induced levels of p-Smad2 and p-ERK1/2, as well as ß-catenin translocation into the nucleus. Furthermore, fucoidan suppressed xenograft tumor growth in vivo. CONCLUSION: Fucoidan displays anti-proliferation and anti-fibrotic effects and exerts protective effects against ULs development.


Assuntos
Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Polissacarídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Fibronectinas/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Leiomioma/tratamento farmacológico , Leiomioma/metabolismo , Leiomioma/patologia , Camundongos , Camundongos Nus , Polissacarídeos/uso terapêutico , Ratos , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta3/farmacologia , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia , Vimentina/metabolismo
4.
Int J Mol Sci ; 18(10)2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28934130

RESUMO

Ovarian cancer is one of the commonest gynecologic malignancies, which has a poor prognosis for patients at the advanced stage. Isoliquiritigenin (ISL), an active flavonoid component of the licorice plant, previously demonstrated antioxidant, anti-inflammatory, and tumor suppressive effects. In this study, we investigated the antitumor effect of ISL on human ovarian cancer in vitro using the human ovarian cancer cell lines, OVCAR5 and ES-2, as model systems. Our results show that ISL significantly inhibited the viability of cancer cells in a concentration- and time-dependent manner. Flow cytometry analysis indicated that ISL induced G2/M phase arrest. Furthermore, the expression of cleaved PARP, cleaved caspase-3, Bax/Bcl-2 ratio, LC3B-II, and Beclin-1 levels were increased in western blot analysis. To clarify the role of autophagy and apoptosis in the effect of ISL, we used the autophagy inhibitor-3-methyladenine (3-MA) to attenuate the punctate fluorescence staining pattern of the p62/sequestosome 1 (SQSTM1, red fluorescence) and LC3 (green fluorescence) proteins after ISL treatment, and 3-MA inhibited the cytotoxicity of ISL. These findings provide new information about the link between ISL-induced autophagy and apoptosis and suggest that ISL is a candidate agent for the treatment of human ovarian cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Chalconas/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacologia , Apoptose/efeitos dos fármacos , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Proteína X Associada a bcl-2/agonistas , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
5.
Mol Carcinog ; 52(3): 183-94, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22086658

RESUMO

Pemetrexed, a new-generation antifolate, has demonstrated promising single-agent activity in front- and second-line treatments of non-small cell lung cancer. However, the molecular mechanism of pemetrexed-mediated antitumor activity remains unclear. The current study shows that pemetrexed induced DNA damage and caspase-2, -3, -8, and -9 activation in A549 cells and that treatment with caspase inhibitors significantly abolished cell death, suggesting a caspase-dependent apoptotic mechanism. The molecular events of pemetrexed-mediated apoptosis was associated with the activation of ataxia telangiectasia mutated (ATM)/p53-dependent and -independent signaling pathways, which promoted intrinsic and extrinsic apoptosis by upregulating Bax, PUMA, Fas, DR4, and DR5 and activating the caspase signaling cascade. Supplementation with dTTP allowed normal S-phase progression and rescued apoptotic death in response to pemetrexed. Overall, our findings reveal that the decrease of thymidylate synthase and the increase of Bax, PUMA, Fas, DR4, and DR5 genes may serve as biomarkers for predicting responsiveness to pemetrexed.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Glutamatos/farmacologia , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Serina-Treonina Quinases/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Caspases/metabolismo , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Guanina/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Pemetrexede , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Nucleotídeos de Timina/farmacologia
6.
Food Nutr Res ; 672023.
Artigo em Inglês | MEDLINE | ID: mdl-36794014

RESUMO

Background: Breast cancer is one of the most prevalent cancers in women. Its pathology comprises tumor cells and nearby stromal cells, accompanied by cytokines and stimulated molecules, resulting in a favorable microenvironment for tumor progression. Lunasin is a seed peptide with multiple bioactivities derived from seeds. However, the chemopreventive effect of lunasin on different characteristics of breast cancer has not been fully explored. Objective: This study aims to explore the chemopreventive mechanisms of lunasin through inflammatory mediators and estrogen-related molecules in breast cancer cells. Design: Estrogen-dependent MCF-7 and independent MDA-MB-231 breast cancer cells were used. The ß-estradiol was used to mimic physiological estrogen. The gene expression, mediator secretion, cell vitality, and apoptosis impacting breast malignancy were explored. Results: Lunasin did not affect normal MCF-10A cell growth but inhibited breast cancer cell growth, increased interleukin (IL)-6 gene expression and protein production at 24 h, and decreased its secretion at 48 h. In both breast cancer cells, aromatase gene and activity and estrogen receptor (ER)α gene expression were decreased by lunasin treatment, while ERß gene levels were significantly increased in MDA-MB-231 cells. Moreover, lunasin decreased vascular endothelial growth factor (VEGF) secretion and cell vitality and induced cell apoptosis in both breast cancer cell lines. However, lunasin only decreased leptin receptor (Ob-R) mRNA expression in MCF-7 cells. Additionally, ß-estradiol increased MCF-7-cell proliferation but not the proliferation of other cells; in particular, lunasin still inhibited MCF-7-cell growth and cell vitality in the presence of ß-estradiol. Conclusion: Seed peptide lunasin inhibited breast cancer cell growth by regulating inflammatory, angiogenic, and estrogen-related molecules, suggesting that lunasin is a promising chemopreventive agent.

7.
J Food Drug Anal ; 31(4): 664-682, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38526823

RESUMO

Dietary factors and chronic hyperglycemia are linked to the formation of advanced glycation end products (AGEs) and prostate cancer (PCa) risk. The activation of the receptor for AGEs (RAGE) acts as a bridge between various RAGE ligands and certain malignancies. This study showed that the interaction of AGEs and RAGE promoted PCa cell proliferation, invasion, and autophagy-mediated survival in response to chemotherapeutic agents. RAGE-overexpressed PCa cells underwent epithelial-mesenchymal transition and showed increased cancer stem cell-like properties. In mouse xenograft models, RAGE-overexpressed cells showed more substantial tumorigenic capacity than parental cells, whereas RAGE knockdown decreased tumorigenicity. The clinical data validated a positive correlation between high AGE and RAGE expressions with poor clinical outcomes. Our findings suggest that the AGE-RAGE axis facilitates PCa progression and aggressiveness. Prostatic AGEs and RAGE expression levels are associated with PCa prognosis. Adherence to a reduced-AGE diet and targeting RAGE are potential approaches to complement and synergize with the current PCa therapies.


Assuntos
Relevância Clínica , Neoplasias da Próstata , Masculino , Humanos , Camundongos , Animais , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Prognóstico , Modelos Animais de Doenças
8.
Nutrients ; 15(18)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37764747

RESUMO

Cajanus cajan (L.) Millsp., also known as pigeon pea, has roots that have exhibited much pharmacological potential. The present study was conducted to assess the safe dose of the ethanolic extract of C. cajan roots (EECR95) and to analyze the main soy isoflavones contents. In vitro, we investigated the mutagenicity and cytotoxic effect of EECR95 on Salmonella typhimurium-TA98 and TA100 (by Ames tests) and RAW 264.7, L-929, and HGF-1 cell lines (by MTT tests) for 24 h of incubation. We found no mutagenic or cytotoxic effects of EECR95. After administration of 0.2 or 1.0 g/kg bw of EECR95 to both male and female Wistar rats for 90 days, there were no significant adverse effects on the behaviors (body weight, water intake, and food intake), organ/tissue weights, or immunohistochemical staining, and the urine and hematological examinations of the rats were within normal ranges. EECR95 potentially decreases renal function markers in serum (serum uric acid, BUN, CRE, and GLU) or liver function markers (cholesterol, triglyceride, and glutamic-pyruvate-transaminase (GPT)). We also found that EECR95 contained five soy isoflavones (genistein, biochanin A, daidzein, genistin, and cajanol), which may be related to its hepatorenal protection. Based on the high dose (1.0 g/kg bw) of EECR95, a safe daily intake of EECR95 for human adults is estimated to be 972 mg/60 kg person/day.


Assuntos
Antineoplásicos , Cajanus , Isoflavonas , Adulto , Masculino , Humanos , Feminino , Animais , Ratos , Cajanus/química , Ratos Wistar , Ácido Úrico , Isoflavonas/farmacologia , Rim/fisiologia
9.
Nutrients ; 15(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36678147

RESUMO

With age, protein glycation in organisms increases continuously. Evidence from many studies shows that the accumulation of glycated protein is highly correlated with biological aging and the development of aging-related diseases, so developing a dietary agent to attenuate protein glycation is very meaningful. Previous studies have indicated that lactic acid bacteria-fermented products have diverse biological activities especially in anti-aging, so this study was aimed to investigate the inhibitory effect of the fermented supernatants of Lactobacillus plantarum GKM3 (GKM3) and Bifidobacterium lactis GKK2 (GKK2) on protein glycation. The results show that GKM3- and GKK2-fermented supernatants can significantly inhibit protein glycation by capturing a glycation agent (methylglyoxal) and/or protecting functional groups in protein against methylglyoxal-induced responses. GKM3- and GKK2-fermented supernatants can also significantly inhibit the binding of glycated proteins to the receptor for advanced glycation end products (RAGE). In conclusion, lactic acid bacteria fermentation products have the potential to attenuate biological aging by inhibiting protein glycation.


Assuntos
Bifidobacterium animalis , Lactobacillus plantarum , Lactobacillus plantarum/metabolismo , Proteínas Glicadas , Reação de Maillard , Aldeído Pirúvico/metabolismo , Fermentação
10.
BMJ Open ; 13(3): e070647, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36898750

RESUMO

OBJECTIVES: Earlier research has evaluated the non-medical costs after lung cancer diagnosis. This study estimated the time costs and transportation costs associated with low-dose CT (LDCT) screening and diagnostic lung procedures in Taiwan. DESIGN: Cross-sectional study. SETTING: A tertiary referral medical centre. PARTICIPANTS AND INTERVENTIONS: The study participants were individuals aged 50-80 years who underwent LDCT screening or diagnostic lung procedures between 2021 and 2022. Participants completed a questionnaire including items on time spent on receiving care, time spent on travel and its cost and time taken off from work by the participant and any accompanying caregiver. OUTCOME MEASURES: Time costs were valued using the age- and sex-specific average daily wage for employed participants/caregivers. Costs of informal healthcare sector consisted of time cost of the participant, transportation cost and time cost of the caregiver. RESULTS: A total of 209 participants who underwent LDCT screening (n=84) or non-surgical (n=12) or surgical (n=113) diagnostic lung procedures for the first time were enrolled. Considering the purchasing power parity, the average costs of informal healthcare sector were US$126.4 (95% CI 101.6 to 151.2), US$290.7 (95% CI 106.9 to 474.5) and US$749.8 (95% CI 567.3 to 932.4), respectively, for LDCT screening, non-surgical procedures and surgical procedures. CONCLUSIONS: This study estimated time and transportation costs associated with LDCT screening and diagnostic lung procedures, which could be used for future analysis of cost-effectiveness of lung cancer screening in Taiwan.


Assuntos
Neoplasias Pulmonares , Masculino , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Estudos Transversais , Detecção Precoce de Câncer/métodos , Taiwan , Tomografia Computadorizada por Raios X/métodos , Pulmão , Programas de Rastreamento/métodos
11.
Food Sci Nutr ; 11(4): 1931-1939, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37051351

RESUMO

Diabetes mellitus (DM) is often accompanied by clinical complications such as sarcopenia. Previous studies have indicated that oxidative stress and insulin resistance (IR) are highly associated with the pathogenesis of diabetic myopathy. α-lipoic acid (ALA), a potent biological antioxidant, exists abundantly in a variety of plants and vegetables. This study aimed to investigate the ameliorative effect of ALA on muscle atrophy in type 2 diabetic rats induced by high-fat diet feeding (HFD) plus streptozotocin (STZ) injection. The HFD/STZ-induced diabetic rats were orally administered 50, 100, or 200 mg/kg body weight ALA once a day for 13 weeks. The results showed that ALA at the tested concentrations significantly increased the soleus muscle mass and muscle fibers in diabetic rats. Proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, were found to decrease in both the serum and muscle of ALA-treated diabetic rats. ALA significantly reduced the protein-expression levels of phosphorylated c-Jun N-terminal kinase (pJNK)/JNK, forkhead box O3 (FOXO3), and muscle ring-finger protein-1 (Murf1); whereas, it enhanced the protein-expression levels of phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT)/AKT, myogenin determination gene D (MyoD), the mechanistic target of rapamycin (mTOR), and myosin heavy chain (MyHC) in the soleus muscle of diabetic rats. The results from this study suggested that ALA treatment may preserve soleus muscle mass, alleviate muscle atrophy by suppressing the TNF-α/JNK pathway, and ameliorate the PI3K/AKT pathway in HFD/STZ-induced type 2 diabetic rats.

12.
IEEE Trans Vis Comput Graph ; 28(11): 3585-3595, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36048981

RESUMO

Gaze-based interaction is a fast and ergonomic type of hands-free interaction that is often used with augmented and virtual reality when pointing at targets. Such interaction, however, can be cumbersome whenever user, tracking, or environmental factors cause eye tracking errors. Recent research has suggested that fallback modalities could be leveraged to ensure stable interaction irrespective of the current level of eye tracking error. This work thus presents Weighted Pointer interaction, a collection of error-aware pointing techniques that determine whether pointing should be performed by gaze, a fallback modality, or a combination of the two, depending on the level of eye tracking error that is present. These techniques enable users to accurately point at targets when eye tracking is accurate and inaccurate. A virtual reality target selection study demonstrated that Weighted Pointer techniques were more performant and preferred over techniques that required the use of manual modality switching.


Assuntos
Gráficos por Computador , Movimentos Oculares
13.
IEEE Trans Image Process ; 30: 374-385, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33186111

RESUMO

The paper proposes a solution to effectively handle salient regions for style transfer between unpaired datasets. Recently, Generative Adversarial Networks (GAN) have demonstrated their potentials of translating images from source domain X to target domain Y in the absence of paired examples. However, such a translation cannot guarantee to generate high perceptual quality results. Existing style transfer methods work well with relatively uniform content, they often fail to capture geometric or structural patterns that always belong to salient regions. Detail losses in structured regions and undesired artifacts in smooth regions are unavoidable even if each individual region is correctly transferred into the target style. In this paper, we propose SDP-GAN, a GAN-based network for solving such problems while generating enjoyable style transfer results. We introduce a saliency network, which is trained with the generator simultaneously. The saliency network has two functions: (1) providing constraints for content loss to increase punishment for salient regions, and (2) supplying saliency features to generator to produce coherent results. Moreover, two novel losses are proposed to optimize the generator and saliency networks. The proposed method preserves the details on important salient regions and improves the total image perceptual quality. Qualitative and quantitative comparisons against several leading prior methods demonstrates the superiority of our method.

14.
Thorac Cancer ; 12(22): 3068-3071, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34623764

RESUMO

C-ros oncogene 1 receptor tyrosine kinase (ROS1) rearrangement has been detected in patients with advanced non-small cell lung cancer (NSCLC). Although ROS1 tyrosine kinase inhibitors (TKIs) provide a survival benefit for patients with ROS1-rearranged advanced NSCLC, subsequent therapy remains limited. Small cell transformation is an important mechanism of drug resistance in epidermal growth factor receptor-mutant NSCLC. However, its significance in mediating ROS1 resistance has not been determined yet. Here, we present the case of a 63-year-old man with ROS1-rearranged advanced NSCLC who had disease progression with small cell transformation of the mediastinal lymph node after 8 months of treatment with crizotinib. More importantly, fluorescence in situ hybridization of post-progression tumor biopsy demonstrated retention of ROS1 rearrangement. Tissue biopsy remains indispensable for patients who acquire resistance to ROS1 TKIs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Transformação Celular Neoplásica/genética , Resistencia a Medicamentos Antineoplásicos/genética , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Carcinoma de Pequenas Células do Pulmão/genética
15.
J Agric Food Chem ; 67(12): 3323-3332, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30832473

RESUMO

High mobility group box 1 (HMGB1) is upregulated in nearly every tumor type. Importantly, clinical evidence also proposed that HMGB1 is particularly increased in metastatic prostate cancer patients. Besides, a growing number of studies highlighted that HMGB1 could be a successful therapeutic target for prostate cancer patients. Glycyrrhizin is a novel pharmacological inhibitor of HMGB1 that may repress prostate cancer metastasis. This research was aimed to investigate the effect of glycyrrhizin on inhibition of HMGB1-induced epithelial-to-mesenchymal transition (EMT), a key step of tumor metastasis, in prostate cancer cells. In this study, HMGB1 knock-downed DU145 prostate cancer cells were used. Silencing the HMGB1 gene expression triggered a change of cell morphology to a more epithelial-like shape, which was accompanied by a reduction of Cdc42/GSK-3ß/Snail and induction of E-cadherin levels estimated by immunoblotting. Furthermore, HMGB1 facilitated cell migration and invasion via downstream signaling, whereas HMGB1 targeting by 10 mM ethyl pyruvate effectively inhibited EMT characteristics. Interestingly, cell migration capacity induced by HMGB1 in DU145 cells was abolished in a dose-dependent effect of 25-200 µM glycyrrhizin treatment. In conclusion, glycyrrhizin successfully inhibited HMGB1-induced EMT phenomenon, which suggested that glycyrrhizin may serves as a therapeutic agent for metastatic prostate cancer.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Ácido Glicirrízico/farmacologia , Proteína HMGB1/metabolismo , Neoplasias da Próstata/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteína HMGB1/genética , Humanos , Masculino , Próstata/efeitos dos fármacos , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/fisiopatologia , Caramujos/genética , Caramujos/metabolismo
16.
Neurotoxicology ; 29(6): 1016-22, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18706441

RESUMO

Methylglyoxal is a reactive dicarbonyl compound generated as an intermediate of glycolysis during the physical glycation in the diabetic condition. It is considered to be a potent precursor of advanced glycation end products (AGEs) formation. Methylglyoxal itself and methylglyoxal-derived AGEs have been commonly implicated in the development of diabetic neuropathy. Our previous study indicated that vanillic acid showed an inhibitory effect against methylglyoxal-mediated Neuro-2A cell apoptosis, suggesting that vanillic acid might possess cytoprotective properties in the prevention of diabetic neuropathy complication. In this study, the effects of vanillic acid on the methylglyoxal-mediated glycation system involved in the progression of Neuro-2A cell apoptosis were further investigated. Our findings indicated that methylglyoxal-induced Neuro-2A cell apoptosis was mediated through the possible glycation mechanism of oxidative stress, activation of the MAPK signaling pathway (p38 and JNK) and oxidation-sensitive protein expression (PKC and p47(phox)) and methylglyoxal-derived N-epsilon-(carboxymethyl)lysine (CML) formation. Vanillic acid, however, suppressed methylglyoxal-induced Neuro-2A cell apoptosis via inhibition of glycation mechanisms including ROS, p38 and JNK, PKC and p47(phox), and methylglyoxal-derived CML formation. In the present study, we established the first evidence that vanillic acid might contribute to the prevention of the development of diabetic neuropathy by blocking the methylglyoxal-mediated intracellular glycation system.


Assuntos
Apoptose/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Aldeído Pirúvico/toxicidade , Ácido Vanílico/farmacologia , Animais , Anexina A5/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Neuroblastoma , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Free Radic Biol Med ; 115: 436-446, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29269310

RESUMO

Methylglyoxal (MG), a highly reactive carbonyl species (RCS) with pro-oxidant and proinflammatory properties, may be a colon tumor-promoting factor in food and biological systems. In the present study, we found that consumption of MG significantly deteriorated azoxymethane (AOM)-induced colonic preneoplastic lesions in ICR mice, in which biomarkers of oxidative stress and inflammation within the body and feces induced by MG-fueled carbonyl stress may have played important roles. Interestingly, exposure to MG also led to increases in the serum low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio and fecal bile acid levels in mice, which may be critical factors involved in MG-induced colonic lesions. Additionally, MG treatment (50mg/kg body weight (BW); intraperitoneally) promoted tumor growth of CT26 isografts in mice partly by carbonyl stress-evoked protumorigenic responses, including low-grade inflammation and oxidative stress. Furthermore, primary tumor cells isolated from mice with MG-induced CT26 isografts had greater proliferative and migratory activities as well as stem-like properties compared to those isolated from the vehicle controls. Excitingly, enhanced expression or activation of proteins that modulate cell survival, proliferation, or migration/invasion was also observed in those cells. In conclusion, it is conceivable that MG-induced carbonyl stress may be the pivotal promoter involved in colon cancer progression.


Assuntos
Carcinógenos/administração & dosagem , Neoplasias Colorretais/patologia , Aldeído Pirúvico/administração & dosagem , Animais , Azoximetano/toxicidade , Carcinogênese , Linhagem Celular , LDL-Colesterol/metabolismo , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Estresse Oxidativo , Lesões Pré-Cancerosas , Transplante Isogênico
18.
J Agric Food Chem ; 66(9): 2065-2070, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29421872

RESUMO

In the last 20 years, the effects of advanced glycation end products (AGEs) on health have received increasing attention. High AGE levels in the body correlate with the progression of many diseases, such as diabetes, cardiovascular disease, and some cancers. However, whether AGEs are a cause of these diseases or represent accompanying symptoms of these diseases still needs to be elucidated by more comprehensive research. Recently, many researchers have begun to investigate the effects of AGE intake-induced variations of gut microbiota on disease progression, which will further explain the impact of AGEs on health and open a new chapter in AGE research.


Assuntos
Doença/etiologia , Produtos Finais de Glicação Avançada/efeitos adversos , Animais , Progressão da Doença , Microbioma Gastrointestinal , Produtos Finais de Glicação Avançada/metabolismo , Humanos
19.
J Food Drug Anal ; 25(1): 84-92, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911546

RESUMO

Advanced glycation end products (AGEs) are substances composed of amino groups of proteins and reducing sugars. The initial and propagation phases of the glycation process are accompanied by the production of a large amount of free radicals, carbonyl species, and reactive dicarbonyl species, of which, methylglyoxal (MG) is the most reactive and can cause dicarbonyl stress, influencing normal physiological functions. In the advanced phase, the production of AGEs and the interaction between AGEs and their receptor, RAGE, are also considered to be among the causes of chronic diseases, oxidative stress, and inflammatory reaction. Till date, multiple physiological activities of polyphenols have been confirmed. Recently, there have been many studies discussing the ability of polyphenols to suppress the MG and AGEs formation, which was also confirmed in some in vivo studies. This review article collects recent literatures concerning the effects of polyphenols on the generation of MG and AGEs through different pathways and discusses the feasibility of the inhibition of glycative stress and dicarbonyl stress by polyphenols.


Assuntos
Polifenóis/química , Radicais Livres , Produtos Finais de Glicação Avançada , Estresse Oxidativo , Aldeído Pirúvico
20.
Int J Oncol ; 50(2): 736-744, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28101572

RESUMO

The progression of colorectal cancer has been reported to have a positive correlation with the combination of hyperglycemia and hyperinsulinemia in diabetic patients, leading to a lower survival rate. However, how insulin acts on colorectal cancer remains not well understood. The purpose of this study was to explore the effect of insulin on colon cancer cell proliferation and its underlying molecular signaling as well as the impact of insulin-induced in vitro metastasis. Our results showed that insulin markedly promoted cell proliferation, migration and anchorage-independent growth in human colon cancer HCT-116 cells. Insulin­regulated insulin receptors (IRs) stimulate insulin receptor substrate 1 (IRS-1) and interact with the downstream signals, causing a rise in HCT-116 cell proliferation. Moreover, insulin significantly induced the migration ability of HCT-116 cells. The metastatic ability of matrix metalloproteinase-2 (MMP-2) mRNA and activity was activated by insulin. Overall, insulin-triggered cell proliferation and metastatic effects on colorectal cancer cells are mediated by IRS-1 and downstream molecules and by increasing phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling. Therefore, insulin induction might have the potential to induce colorectal cancer progression in diabetes patients.


Assuntos
Neoplasias Colorretais/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Insulina/farmacologia , Metaloproteinase 2 da Matriz/genética , Receptor de Insulina/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Metástase Neoplásica , Transdução de Sinais/efeitos dos fármacos
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