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1.
Genomics ; 115(6): 110730, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37866658

RESUMO

RNA-binding proteins (RBPs), which are key effectors of gene expression, play critical roles in inflammation and immune regulation. However, the potential biological function of RBPs in ankylosing spondylitis (AS) remains unclear. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of five patients with AS and three healthy persons by RNA-seq, obtained differentially expressed RBPs by overlapping DEGs and RBPs summary table. RIOK3 was selected as a target RBP and knocked down in mouse bone marrow mesenchymal stem cells (mBMSCs), and transcriptomic studies of siRIOK3 mBMSCs were performed again using RNA-seq. Results showed that RIOK3 knockdown inhibited the expression of genes related to osteogenic differentiation, ribosome function, and ß-interferon pathways in mBMSCs. In vitro experiments have shown that RIOK3 knockdown reduced the osteogenic differentiation ability of mBMSCs. Collectively, RIOK3 may affect the differentiation of mBMSCs and participate in the pathogenesis of AS, especially pathological bone formation.


Assuntos
Células-Tronco Mesenquimais , Espondilite Anquilosante , Animais , Humanos , Camundongos , Diferenciação Celular , Células Cultivadas , Leucócitos Mononucleares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética , Espondilite Anquilosante/genética , Espondilite Anquilosante/metabolismo , Espondilite Anquilosante/patologia
2.
Technol Health Care ; 31(5): 1671-1681, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37092189

RESUMO

BACKGROUND: Despite advances in the treatment of sepsis over time, this condition remains both a serious threat and a cause of death among critical patients. OBJECTIVE: This study aimed to explore the role of the nuclear factor kappa B (NF-κB) signaling pathway in the development of septic cardiomyopathy in rats with sepsis. METHOD: A total of 32 Sprague Dawley rats were randomized into a sham operation group and three groups with sepsis, which were tested at one of the following time-points: 3, 6, or 12 h. Each group included eight rats. Sepsis models were created via cecal ligation and puncture procedures. All the study rats had the following cardiac parameters and serum levels measured at either 3, 6, or 12 h after the operation (according to their assigned group): heart rate, left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure rise (+dP/dtmax) and fall (-dP/dtmax), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and cardiac troponin I (cTnI). The myocardium of the left ventricle was collected and subjected to hematoxylin and eosin staining to observe the changes in pathological morphology. The expression of toll-like receptor 4 (TLR4) and NF-κB in the myocardium were detected by western blot analysis. RESULTS: Compared with the sham operation group, the rats in the sepsis subgroups exhibited significantly lower values for all the cardiac parameters measured, including the heart rate (sham operation group = 386.63 ± 18.62 beats per minute [bpm], sepsis 3-h group = 368.38 ± 12.55 bpm, sepsis 6-h group = 341.75 ± 17.05 bpm, sepsis 12-h group = 302.13 ± 21.15 bpm), LVSP (sham operation group = 125.50 ± 11.45 mmHg, sepsis 3-h group = 110.88 ± 7.51 mmHg, sepsis 6-h group = 100.00 ± 15.06 mmHg, sepsis 12-h group = 91.38 ± 14.73 mmHg), +dp/dtmax (sham operation group = 7137.50 ± 276.44 mm Hg/sec, sepsis 3-h group = 5745.00 ± 346.16 mm Hg/sec, sepsis 6-h group = 4360.00 ± 312.04 mm Hg/sec, sepsis 12-h group = 2871.25 ± 443.99 mm Hg/sec), and -dp/dtmax (sham operation group = 6363.75 ± 123.86 mm Hg/sec, sepsis 3-h group = 6018.75 ± 173.49 mm Hg/sec, sepsis 6-h group = 5350.00 ± 337.89 mm Hg/sec, sepsis 12-h group = 4085.00 ± 326.76 mm Hg/sec). They also displayed significantly higher levels of serum cytokines, including TNF-α (sham operation group = 14.72 ± 2.90 pg/mL, sepsis 3-h group = 34.90 ± 4.79 pg/mL, sepsis 6-h group = 24.91 ± 2.57 pg/mL, sepsis 12-h group 22.06 ± 3.11 pg/mL), IL-1ß (sham operation group = 42.25 ± 16.91, 3-h group = 112.25 ± 13.77, sepsis 6-h group = 207.90 ± 22.64, sepsis 12-h group = 157.18 ± 23.06), IL-6 (sham operation group = 39.89 ± 5.74, sepsis 3-h group = 78.27 ± 9.31, sepsis 6-h group = 123.75 ± 13.11, sepsis 12-h group = 93.21 ± 8.96), and cTnI (sham operation group = 0.07 ± 0.03 ng/mL, sepsis 3-h group = 0.18 ± 0.06 ng/mL, sepsis 6-h group = 0.67 ± 0.19 ng/mL, sepsis = 12-h group 1.28 ± 0.10 ng/mL). The rats in the sepsis groups exhibited pathological changes in the myocardium, which deteriorated gradually over time. The animals in all the sepsis groups exhibited significantly higher levels of TLR4 and NF-κB protein expression compared with the sham group. The TLR4 protein expressions were 0.376 in the sham operation group, 0.534 in the sepsis 3-h group, 0.551 in the sepsis 6-h group, and 0.719 in the sepsis 12-h group. The NF-κB protein expressions were 0.299 in the sham operation group, 0.488 in the sepsis 3-h group, 0.516 in the sepsis 6-h group, and 0.636 in the sepsis 12-h group. CONCLUSION: Sepsis can lead to myocardial injury and cardiac dysfunction. This may be related to the activation of the NF-κB intracellular signal transduction pathway and the release of inflammatory factors as a result of lipopolysaccharides acting on TLR4 during the onset of sepsis.


Assuntos
Cardiomiopatias , Sepse , Humanos , Ratos , Animais , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa , Interleucina-6 , Transdução de Sinais , Cardiomiopatias/etiologia , Sepse/complicações
3.
Acta Biochim Pol ; 70(1): 153-162, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36929708

RESUMO

A great many circular RNAs (circRNAs) are considered key modulators of human malignancies. However, the function of circRNA lysophosphatidic acid receptor 3 (LPAR3) in the radioresistance of prostate cancer (PCa) cells is still uncertain. circLPAR3, microRNA (miR)-329-3p, and JPT1 expression in PCa tissues and cells were detected by real-time quantitative PCR or western blot. Cell proliferation was detected by CCK-8 (cell proliferation assay) and colony formation assay, apoptosis was by flow cytometry, and migration and invasion ability were by Transwell assay. Cell glycolysis was analyzed by glucose uptake, lactate production, and ATP metabolism. Under different doses of radiation, the radiosensitivity of PCa cells was detected by colony formation assay. The relationship between circLPAR3, miR-513b-5p, and JPT1 was confirmed by dual luciferase reporter gene detection and RIP assay. The data presented that circLPAR3 and JPT1 expression was elevated in PCa, while miR-513b-5p expression was reduced. Repression of circLPAR3 depressed cell advancement, and restrained glycolysis, but enhanced the radiosensitivity of PCa cells. CircLPAR3's target miRNA was miR-513b-5p which targeted JPT1. Elevated JPT1 reversed the repressive effects of circLPAR3 knockdown or miR-513b-5p overexpression on PCa advancement, glycolysis, and radiosensitivity. In summary, the knockdown of circLPAR3 reduces glycolysis, but promotes PCa radiosensitivity via the miR-513b-5p/JPT1 axis, discovering a novel mechanism in PCa progression.


Assuntos
MicroRNAs , Neoplasias da Próstata , Humanos , Masculino , RNA Circular/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Glicólise/genética , Proliferação de Células/genética , Ácido Láctico , MicroRNAs/genética , Tolerância a Radiação/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
4.
J Nat Prod ; 85(8): 1945-1958, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-35943432

RESUMO

Steviol is an ent-kaurene diterpenoid with interesting pharmacological activity. Several steviol derivatives with an exo-methylene cyclopentanone unit were discovered as potent antitumor agents. However, their poor selectivity for tumor cells relative to normal cells reduces their prospects as potential anticancer drugs. In this study, based on previous work, 32 steviol derivatives, including 28 new analogues, were synthesized. Their cytotoxicity against tumor cells and normal cells was evaluated. Several new derivatives, such as 7a, 7h, and 8f, with improved cytotoxic selectivity and antiproliferative activity were obtained, and the structure-activity relationship correlations were investigated. The new compound 8f displayed potent antiproliferative activity against Huh7 cells (IC50 = 2.6 µM) and very weak cytotoxicity against the corresponding normal cells HHL5 (IC50 = 97.0 µM). Further investigation showed that 8f arrested the cell cycle at the G0/G1 phase and caused reactive oxygen species overproduction, decreased mitochondrial membrane potential, and induced apoptosis of Huh7 cells through inhibition of the PI3K/Akt/mTOR and NF-κB pathway as well as upregulation of Bax/Bcl-2 ratio. The present study suggested that 8f is a promising lead compound for new cancer therapies, and the results presented herein may encourage the further modification of steviol for additional derivatives with enhanced efficacy and selectivity.


Assuntos
Antineoplásicos , Diterpenos do Tipo Caurano , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Diterpenos do Tipo Caurano/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Fosfatidilinositol 3-Quinases , Relação Estrutura-Atividade
5.
Front Oncol ; 12: 815952, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35311119

RESUMO

Purpose: This study aimed to develop a nomogram model based on multiparametric magnetic resonance imaging (MRI) radiomics features, clinicopathological characteristics, and blood parameters to predict the progression-free survival (PFS) of patients with nasopharyngeal carcinoma (NPC). Methods: A total of 462 patients with pathologically confirmed nonkeratinizing NPC treated at Sichuan Cancer Hospital were recruited from 2015 to 2019 and divided into training and validation cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) algorithm was used for radiomics feature dimension reduction and screening in the training cohort. Rad-score, age, sex, smoking and drinking habits, Ki-67, monocytes, monocyte ratio, and mean corpuscular volume were incorporated into a multivariate Cox proportional risk regression model to build a multifactorial nomogram. The concordance index (C-index) and decision curve analysis (DCA) were applied to estimate its efficacy. Results: Nine significant features associated with PFS were selected by LASSO and used to calculate the rad-score of each patient. The rad-score was verified as an independent prognostic factor for PFS in NPC. The survival analysis showed that those with lower rad-scores had longer PFS in both cohorts (p < 0.05). Compared with the tumor-node-metastasis staging system, the multifactorial nomogram had higher C-indexes (training cohorts: 0.819 vs. 0.610; validation cohorts: 0.820 vs. 0.602). Moreover, the DCA curve showed that this model could better predict progression within 50% threshold probability. Conclusion: A nomogram that combined MRI-based radiomics with clinicopathological characteristics and blood parameters improved the ability to predict progression in patients with NPC.

6.
Dis Markers ; 2022: 4952812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251372

RESUMO

Colorectal cancer (CRC) remains an important malignancy worldwide with poor prognosis. It has been known that DNA repair genes are involved in the development and progression of various tumors. Therefore, the purpose of this study was to explore DNA repair gene-based prognostic biomarkers for CRC. In this study, the expressing pattern and prognostic values of DNA repair genes in CRC patients were analyzed using TCGA database. GO and KEGG enrichment analyses were conducted to clarify the functional roles of dysregulated genes. We observed 358 differentially expressed DNA repair genes in CRC specimens, including 84 downregulated genes and 275 upregulated genes. 36 survival-related DNA repair genes were correlated with CRC patients' five-year survival, including 6 low-risk genes and 30 high-risk genes. Among the 10 overlapping genes, we focused on SLC6A1 which was highly expressed in CRC, and multivariate analysis confirmed that SLC6A1 expression as well as age and clinical stage could be regarded as an independent predicting factor for CRC prognosis. KEGG assays revealed that SLC6A1 may influence the clinical progression via regulating TGF-beta and PI3K-Akt signaling pathways. In addition, we observed that SLC6A1 was negatively regulated by SLC6A1 methylation, leading to its low expression in CRC specimens. Overall, SLC6A1 is upexpressed in CRC and can be used as a marker of poor prognosis in CRC patients.


Assuntos
Neoplasias Colorretais/genética , Reparo do DNA/genética , Proteínas da Membrana Plasmática de Transporte de GABA , Prognóstico , Transdução de Sinais , Taxa de Sobrevida , Bases de Dados Genéticas/estatística & dados numéricos , Regulação para Baixo , Feminino , Humanos , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Regulação para Cima
7.
Cell Prolif ; 55(2): e13178, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35018683

RESUMO

OBJECTIVES: DNA N6-methyladenine (N6-mA) demethylase Alkbh1 participates in regulating osteogenic differentiation of mesenchymal stem cell (MSCs) and vascular calcification. However, the role of Alkbh1 in bone metabolism remains unclear. MATERIALS AND METHODS: Bone marrow mesenchymal stem cells (BMSCs)-specific Alkbh1 knockout mice were used to investigate the role of Alkbh1 in bone metabolism. Western blot, qRT-PCR, and immunofluorescent staining were used to evaluate the expression of Alkbh1 or optineurin (optn). Micro-CT, histomorphometric analysis, and calcein double-labeling assay were used to evaluate bone phenotypes. Cell staining and qRT-PCR were used to evaluate the osteogenic or adipogenic differentiation of BMSCs. Dot blotting was used to detect the level of N6-mA in genomic DNA. Chromatin immunoprecipitation (Chip) assays were used to identify critical targets of Alkbh1. Alkbh1 adeno-associated virus was used to overexpress Alkbh1 in aged mice. RESULTS: Alkbh1 expression in BMSCs declined during aging. Knockout of Alkbh1 promoted adipogenic differentiation of BMSCs while inhibited osteogenic differentiation. BMSC-specific Alkbh1 knockout mice exhibited reduced bone mass and increased marrow adiposity. Mechanistically, we identified optn as the downstream target through which Alkbh1-mediated DNA m6A modification regulated BMSCs fate. Overexpression of Alkbh1 attenuated bone loss and marrow fat accumulation in aged mice. CONCLUSIONS: Our findings demonstrated that Alkbh1 regulated BMSCs fate and bone-fat balance during skeletal aging and provided a potential target for the treatment of osteoporosis.


Assuntos
Envelhecimento/metabolismo , Homólogo AlkB 1 da Histona H2a Dioxigenase/metabolismo , Diferenciação Celular/fisiologia , DNA/metabolismo , Células-Tronco Mesenquimais/citologia , Adipogenia/fisiologia , Animais , Células da Medula Óssea/citologia , Camundongos , Músculo Esquelético/metabolismo , Osteogênese/fisiologia , Osteoporose/metabolismo
8.
Hepatobiliary Pancreat Dis Int ; 17(6): 531-537, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30424963

RESUMO

BACKGROUND: With the advances of imaging techniques, the detection rate of rare liver tumor is increased. However, the therapeutic strategies of the rare liver tumors remain limited. METHODS: We analyzed twelve pathologically confirmed rare liver tumors in 8 patients. All of the patients underwent ultrasound (US) guided biopsy and subsequent thermal ablation. The tumors were ablated according to the preoperative plans and monitored by real-time US. CT/MRI fused with contrast enhanced US (CEUS) or three-dimensional (3D) US-CEUS images were used to guide and assess the ablation zone more accurately during thermal ablation. The rate of technical efficacy was assessed based on the contrast-enhance CT/MRI (CECT/MRI) results one month after ablation. Local tumor progression (LTP), recurrence and complications were followed up and recorded. RESULTS: Among these twelve nodules, nine were subject to US-guided thermal ablation, whereas the other three inconspicuous nodules were subject to CEUS-guided thermal ablation. Intra-procedure CT/MRI-CEUS or 3D US-CEUS fusion imaging assessments demonstrated that the ablation zone sufficiently covered the original tumor, and no immediate supplementary ablation was required. Additionally, no major complications were observed during the follow-up period. The postoperative CECT/MRI confirmed that the technique success rate was 100%. Within the surveillance period of 13 months, no LTP or recurrence was noted. CONCLUSIONS: US-guided thermal ablation was feasible and safe for rare liver tumors. The use of fusion imaging technique might make US-guided thermal ablation as effective as surgical resection, and this technique might serve as a potential therapeutic modality for rare liver tumors in the future.


Assuntos
Técnicas de Ablação/métodos , Neoplasias Hepáticas/cirurgia , Ultrassonografia de Intervenção , Adulto , Meios de Contraste , Feminino , Humanos , Aumento da Imagem , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Doenças Raras
9.
Int J Mol Med ; 40(6): 1649-1656, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29039492

RESUMO

This study aimed to investigate the role of focal adhesion kinase (FAK) signaling in the inhibitory effects of black rice anthocyanins (BRACs) on human epidermal growth factor receptor-2 (HER-2)-positive human breast cancer cell metastasis, using the MCF-10A, MCF-7 and MDA-MB-453 cells. BRACs exerted an anti-metastatic effect on the HER-2-positive breast cancer cells. The effects of BRACs on the proliferation of the MDA-MB-453 cells were examined by cell counting kit-8 assay. A wound-healing assay was used to examine the effects of BRACs on the migration of the breast cancer cells. BRACs interrupted migration and invasion. BRACs decreased the migration distance of the HER-2-positive human breast cancer cells, MDA-MB-453, by 37% compared with the cells in the untreated group. They also reduced the number of invading MDA-MB-453 cells by 68%. In addition, BRACs exerted an inhibitory effect on epithelial-mesenchymal transition. Western blot analysis revealed that BRACs decreased the phosphorylation of FAK, cSrc and p130Cas. The FAK inhibitor, Y15, was also used to further evaluate the role of FAK signaling in the anti-metastatic effects of BRACs on MDA-MB-453 cells. The results of western blot analysis revealed that BRACs increased the expression of the epithelial marker, E-cadherin, and decreased the expression of the mesenchymal markers, fibronectin and vimentin, in the MDA-MB­453 cells. In addition, BRACs decreased the interaction between HER-2 and FAK, FAK and cSrc, cSrc and p130Cas, and between FAK and p130Cas. These results suggest that BRACs suppress the metastasis of HER-2-positive breast cancer in vitro, and that the cSrc/FAK/p130Cas pathway plays a vital role in this inhibitory effect.


Assuntos
Antocianinas/farmacologia , Neoplasias da Mama/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Oryza/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Feminino , Adesões Focais , Humanos , Extratos Vegetais/farmacologia , Receptor ErbB-2 , Transdução de Sinais/efeitos dos fármacos
10.
Biomed Res Int ; 2015: 414250, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26649302

RESUMO

Overexpression of human epidermal growth factor receptor 2 (HER2) drives the biology of 30% of breast cancer cases. As a transducer of HER2 signaling, RAS/RAF/MAPK pathway plays a pivotal role in the development of breast cancer. In this study, we examined the molecular mechanisms underlying the chemopreventive effects of black rice anthocyanins (BRACs) extract and identified their molecular targets in HER2(+) breast cancer cells. Treatment of MDA-MB-453 cells (HER2(+)) with BRACs inhibited cell migration and invasion, suppressed the activation of mitogen-activated protein kinase kinase kinase (RAF), mitogen-activated protein kinase kinase (MEK), and c-Jun N-terminal kinase (JNK), and downregulated the secretion of matrix metalloproteinase 2 (MMP2) and MMP9. BRACs also weakened the interactions of HER2 with RAF, MEK, and JNK proteins, respectively, and decreased the mRNA expression of raf, mek, and jnk. Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment. Transient transfection with small interfering RNAs (siRNAs) specific for raf, mek, and jnk inhibited their mRNA expression in MDA-MB-453 cells. Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone. In summary, our study suggested that BRACs suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway.


Assuntos
Antocianinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , MAP Quinase Quinase Quinase 1/biossíntese , Quinases raf/biossíntese , Proteínas ras/biossíntese , Antocianinas/química , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MAP Quinase Quinase Quinase 1/genética , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Invasividade Neoplásica/genética , Metástase Neoplásica , Oryza/química , Receptor ErbB-2/genética , Transdução de Sinais/efeitos dos fármacos , Quinases raf/genética , Proteínas ras/genética
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(11): 3058-62, 2015 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-26978908

RESUMO

Propolis possesses functions of antibacterial, antiviral, anticancer, and liver protection, and is known as the "purple gold", however, the phenomenon which making and selling of counterfeit are growing in intensity. In order to establish a authenticity and quality of propolis evaluation model, in this paper, forty-one Chinese propolis, one proplis from United States and two tree gums were used for experimental materials. The infrared spectrum collection was performed by Fourier transform infrared spectrometer, and principal component analysis (PCA) was used for data analysis. The result showed that, the intrared spectrum of propolis and tree gum were significantly different. The propolis characteristic peak only appeared in 2500-3500 and 400-1800 cm⁻¹. All propolis had two frequency region of characteristic peaks, 2849.08-2848.53 and 2917.74- 2916.76 cm⁻¹, but tree gum did not have characteristic peak in this region. The characteristic peaks of gum were in 1150-1300 and 1550-1650 cm⁻¹. Differences in these aspects can be used to distinguish propolis and gum, and can be used to identify true and false propolis. We use Qinghai propolis as a standard sample, in 42 samples, the matching degree of other propolis is > 80%. In addition, the result of PCA shows that tree gum and the propolis from different climate zone, or with different colors could be distinguished well. This paper firstly performed analysis on different propolis and gum by infrared spectrum, and a new method, for authenticity and quality of propolis identification, could be developed.


Assuntos
Gomas Vegetais/química , Própole/química , Espectroscopia de Infravermelho com Transformada de Fourier , Árvores
12.
Asian Pac J Cancer Prev ; 15(15): 6219-25, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25124601

RESUMO

BACKGROUND: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. MATERIALS AND METHODS: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. RESULTS: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). CONCLUSIONS: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.


Assuntos
Antocianinas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Oryza/química , Receptor ErbB-2/metabolismo , Animais , Western Blotting , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Células Tumorais Cultivadas , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Cicatrização , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Dig Dis Sci ; 58(11): 3198-206, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23861108

RESUMO

BACKGROUND AND OBJECTIVES: Previous studies have shown that betaine prevents alcohol-induced liver injury and improves liver function. The purpose of this study was to investigate the hepatoprotective effects of betaine on nonalcoholic fatty liver disease (NAFLD) and to observe changes of HMGB1/TLR4 signaling. METHODS: Thirty rats were randomly divided into control, model, and betaine groups. The rats in the model and betaine groups were fed a high-fat diet for 12 weeks to induce an animal model of NAFLD. The rats in the betaine group were then intragastrically administered betaine solution at a dose of 400 mg/kg per day for four weeks. Liver histology was examined. Serum levels of ALT, AST, TC, TG, HDL-C, LDL-C, FFA, HMGB1, NF-κB, TLR4, and tHcy were determined and intrahepatic TC, TG, and Hcy levels were assayed. mRNA expression and protein levels of HMGB1, NF-κB, and TLR4 in liver tissue were also determined. RESULTS: Compared with the control group, rats in the model group developed severe liver injury, accompanied by significant increases in serum levels of ALT, AST, TC, TG, LDL-C, FFA, HMGB1, NF-κB, and TLR4, intrahepatic TC, TG, and Hcy content, histological scores for steatosis, inflammation, and necrosis, and mRNA expression and protein levels of HMGB1, NF-κB, and TLR4, and a significant decrease in serum HDL-C (P < 0.05). Compared with the model group, all these indicators were significantly improved by administration of betaine (P < 0.05). CONCLUSIONS: Betaine effectively protects against high-fat-diet-induced NAFLD and improves liver function; the mechanism is probably related to inhibition of HMGB1/TLR4 signaling pathways.


Assuntos
Betaína/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Gorduras na Dieta/efeitos adversos , Regulação da Expressão Gênica/fisiologia , Domínios HMG-Box/fisiologia , Receptor 4 Toll-Like/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Fígado Gorduroso/prevenção & controle , Feminino , Domínios HMG-Box/genética , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Receptor 4 Toll-Like/genética , Aumento de Peso
14.
J Agric Food Chem ; 61(6): 1189-95, 2013 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-23350869

RESUMO

In the present study, zero-trans α-linolenic acid (ALA) and medium-chain fatty acids (MCFA)-enriched plastic fats were synthesized through enzymatic interesterification reactions from highly hydrogenated soybean oil (HSO), Cinnamomum camphora seed oil (CCSO), and perilla oil (PO). The reactions were performed by incubating the blending mixtures of HSO, CCSO, and PO at different weight ratios (60:40:100, 70:30:100, 80:20:100) using 10% (total weight of substrate) of Lipozyme TL IM at 65 °C for 8 h. After reaction, the physical properties (fatty acids profile, TAG composition, solid fat content, slip melting point, contents of tocopherol, polymorphic forms, and microstructures) of the interesterified products and their physical blends were determined, respectively. Results showed that the fatty acid compositions of the interesterified products and physical blends had no significant changes, while the content of MCFA in both interesterified products and physical blends increased to 8.58-18.72%. Several new types of TAG species were observed in interesterified products (SSL/SLS, PLO/LLS, and OLLn/LnLO/LOLn). It should be mentioned that no trans fatty acids (TFA) were detected in all products. As the temperature increased, the solid fat content (SFC) of interesterified products was obviously lower than that of physical blends. The SFCs of interesterified products (60:40:100, 70:30:100, and 80:20:100, HSO:CCSO:PO) at 25 °C were 6.5%, 14.6%, and 16.5%, respectively, whereas the counterparts of physical blends were 32.5%, 38.5%, and 43.5%, respectively. Meanwhile, interesterified products showed more ß' polymorphs than physical blends, in which ß' polymorph is a favorite form for production of margarine and shortening. Such zero-trans ALA and MCFA-enriched fats may have desirable physical and nutritional properties for shortenings and margarines.


Assuntos
Cinnamomum camphora/química , Ácidos Graxos/química , Ácidos Graxos/síntese química , Tecnologia de Alimentos/métodos , Lipase/química , Óleo de Soja/química , Ácidos Graxos trans/síntese química , Ácido alfa-Linolênico/síntese química , Hidrogenação , Óleos de Plantas/química , Sementes/química , Ácidos Graxos trans/química , Ácido alfa-Linolênico/química
15.
J Food Sci ; 77(4): C454-60, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22515238

RESUMO

It is known that Cinnamomum camphora seed oil (CCSO) is rich in medium-chain fatty acids (MCFAs) or medium-chain triacylglycerols (MCTs). The purpose of the present study was to produce zero-trans MCTs-enriched plastic fat from a lipid mixture (500 g) of palm stearin (PS) and CCSO at 3 weight ratios (PS:CCSO 60:40, 70:30, 80:20, wt/wt) by using lipase (Lipozyme TL IM, 10% of total substrate) as a catalyst at 65 °C for 8 h. The major fatty acids of the products were palmitic acid (C16:0, 42.68% to 53.42%), oleic acid (C18:1, 22.41% to 23.46%), and MCFAs (8.67% to 18.73%). Alpha-tocopherol (0.48 to 2.51 mg/100 g), γ-tocopherol (1.70 to 3.88 mg/100 g), and δ-tocopherol (2.08 to 3.95 mg/100 g) were detected in the interesterified products. The physical properties including solid fat content (SFC), slip melting point (SMP), and crystal polymorphism of the products were evaluated for possible application in shortening or margarine. Results showed that the SFCs of interesterified products at 25 °C were 9% (60:40, PS:CCSO), 18.50% (70:30, PS:CCSO), and 29.2% (80:20, PS:CCSO), respectively. The ß' crystal form was found in most of the interesterified products. Furthermore, no trans fatty acids were detected in the products. Such zero-trans MCT-enriched fats may have a potential functionality for shortenings and margarines which may become a new type of nutritional plastic fat for daily diet.


Assuntos
Cinnamomum camphora/química , Gorduras na Dieta/análise , Margarina/análise , Extratos Vegetais/química , Óleos de Plantas/química , Sementes/química , Triglicerídeos/química , Ascomicetos/enzimologia , Fenômenos Químicos , China , Cromatografia Líquida de Alta Pressão , Gorduras na Dieta/efeitos adversos , Enzimas Imobilizadas/metabolismo , Esterificação , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/química , Proteínas Fúngicas/metabolismo , Lipase/metabolismo , Margarina/efeitos adversos , Extratos Vegetais/metabolismo , Óleos de Plantas/metabolismo , Estereoisomerismo , Ácidos Graxos trans/efeitos adversos , Ácidos Graxos trans/análise , Ácidos Graxos trans/química , Temperatura de Transição , Triglicerídeos/efeitos adversos , Triglicerídeos/metabolismo , Difração de Raios X
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 28(5): 473-5, 2008 May.
Artigo em Chinês | MEDLINE | ID: mdl-18672781

RESUMO

Extract of Tripterygium wilfordi (TW) has obvious effects on anti-inflammation, anti-tumor, anti-fertility and immuno-regulation, and it is broadly applied in various clinical departments. Referred to the gynecologic diseases, clinical therapeutic trials of TW on endometriosis, leiomyoma uteri, dysfunctional uterine bleeding and some tumors of women have been carried out, and it can be proved an effective new drug for the treatment of gynecologic diseases.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Doenças dos Genitais Femininos/tratamento farmacológico , Tripterygium , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Anticoncepcionais Femininos/uso terapêutico , Endometriose/tratamento farmacológico , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Leiomioma/tratamento farmacológico , Metrorragia/tratamento farmacológico
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