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1.
Food Chem ; 305: 125454, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505413

RESUMO

The effects of the (-)-Epigallocatechin gallate (EGCG)-gelatin biofilm treatment (EGT) on microbial composition and quality of tilapia fillets stored at low temperatures were evaluated. The changes in mechanical properties, microbial reproduction, as well as lipid and protein oxidation during fillets storage were determined. The results showed that EGT reduced the microbial count and the relative abundance of the fillets. And EGT delayed the rate of lipid oxidation and protein denaturation in fillets. Compared with the control group, EGT samples had lower K values (74% on 18 d) and biogenic amines (39 mg/kg for putrescine and 50 mg/kg for cadaverine on 21 d). According to sensory evaluation, the shelf life of tilapia fillets was extended by 6 d in the EGT group. Therefore, EGT improved the quality of cryopreserved tilapia fillets and could be considered as a potential method for fish fillet preservation.

2.
Int J Chron Obstruct Pulmon Dis ; 14: 2697-2709, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819402

RESUMO

Purpose: Elastin peptides (EP) can induce lung inflammation and emphysema. Erythromycin has been shown to decrease acute exacerbation frequency and delay lung function decline in chronic obstructive pulmonary disease patients and ameliorate emphysema in murine models; however, the mechanism remains unclear. We aimed to observe the preventive and immunomodulatory effects of erythromycin in a mouse model of EP-induced emphysema. Methods: In the in vivo study, Balb/c mice were treated with EP intranasally on day 0, and then administered erythromycin (100 mg/kg) or vehicle orally on day 1, which was continued every other day. Mice exposed to cigarette smoke were used as an emphysema positive control. The severity of emphysema and inflammation in the lungs of EP-exposed mice with or without erythromycin treatment were observed on day 40 after EP administration. In the in vitro study, naïve CD4+T cells were isolated from healthy mice spleens and stimulated by EP with or without erythromycin incubation. Flow cytometry was used to measure the proportions of Th1, Th17, and Treg cells. ELISA was used to detect cytokine levels of IFN-γ, IL-17, IL-6, and TGF-ß. Transcript levels of Ifnγ, IL17a, and Foxp3 were evaluated by qRT-PCR. Results: After exposure to EP, Th1 and Th17 cell percentages and the levels of inflammatory cytokines increased in vivo and in vitro, while Treg cells decreased in vivo. Erythromycin reduced IFN-γ, IL-17, IL-6 inflammatory cytokines, MLI, and the inflammation score in the lungs of EP-exposed mice. In vitro, erythromycin also limited Th17 and Th1 cell differentiation and downregulated transcript levels of Ifnγ and IL17a in the EP-stimulated CD4+T cells. Conclusion: The Th1 and Th17 cell responses were increased in EP-induced emphysema. Prophylactic use of erythromycin effectively ameliorated emphysema and modulated CD4+T cells responses in EP-induced lung inflammation in mice.

3.
Biomark Med ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729251

RESUMO

Aim: This study profiled differentially expressed long noncoding RNAs (lncRNAs) in lung squamous cell carcinoma (LSCC) to predict LSCC overall survival (OS) using The Cancer Genome Atlas data. Materials & methods: The RNA-seq and clinical dataset of 475 LSCC patients was retrieved from The Cancer Genome Atlas database and statistically analyzed. Results: There were 67 upregulated and 32 downregulated lncRNAs in LSCCs and 12 lncRNAs associated with OS. The seven-lncRNA signature was associated with poor OS and RP11-150O12.6 and CTA-384D8.35 were associated with better OS (p < 0.001). The seven lncRNAs-mRNA interaction network analysis showed their association with 187 protein-coding genes for cancer development, cell migration, adhesion, proliferation, apoptosis, angiogenesis and the MAPK signaling pathways. Conclusion: This seven-lncRNA signature is useful to predict LSCC OS.

4.
Clin Breast Cancer ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31587961

RESUMO

BACKGROUND: Galactography is a primary recommendation in the management of nipple discharge (ND), which may be caused by benign or malignant lesions. We aimed to establish a galactogram grading system (GGS) and investigate its role in identifying breast cancer with ND. PATIENTS AND METHODS: A total of 350 patients were included in our study. All patients received preoperative mammographic galactography successfully and underwent surgery at Qilu Hospital of Shandong University between January 2011 and August 2015. We first performed a retrospective study in a consecutive series of 250 patients with ND to establish a GGS. Then the subsequent consecutive series of 100 patients was analyzed to validate the grading system. RESULTS: Our data showed that the GGS can well assess the risk of a galactogram's being malignant. Galactograms classified into grade I have a lower risk of being malignant, while those classified into grade III have a higher risk of being malignant. Thus, our GGS was useful for distinguishing malignant from benign lesions. CONCLUSION: We established a scoring system for breast disease with ND. This GGS may be a novel approach for identifying breast cancer with ND.

5.
Cell Mol Biol (Noisy-le-grand) ; 65(6): 64-72, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472049

RESUMO

Breast cancer is a malignant tumor that occurs in the glandular epithelial tissues of the breast. It is one of the most common malignant tumors in women. This study was aimed at investigating the role of cell-free DNA (cfDNA) as a potential biomarker for breast cancer diagnosis. Patients with primary breast cancer (n =110) were enrolled in the experimental group, 95 patients with benign breast tumors were in control group 1, while 90 healthy volunteers were in control group 2. Quantitative PCR was used to determine cfDNA concentration and integrity in each group. The cfDNA levels in different groups and their relationship with clinical features of breast cancer patients were analyzed. Receiver operational curves were established to analyze sensitivity and specificity of cfDNA concentration, cfDNA integrity, CEA, CA125 and CA15-3. The cfDNA concentration and cfDNA integrity of the experimental group were significantly higher than those of control groups 1 and 2. The cfDNA concentration and integrity in plasma of experimental group after chemotherapy were significantly lower than those before chemotherapy. While CEA and CA15-3 expressions were significantly correlated with cfDNA concentration, CA125 expression was significantly correlated with cfDNA integrity. Results from ROC curve analysis showed that the sensitivity and specificity of cfDNA concentration and integrity were higher than those of traditional tumor biomarkers. These results indicate that cfDNA concentration and integrity are significantly higher in primary breast cancer patients than in benign breast tumor patients and healthy people. Thus, cfDNA may serve as a potential biomarker of breast cancer.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31546793

RESUMO

Phthalate acid esters (PAEs) are the most frequently utilized synthetic chemical compounds worldwide. They are typical emergent contaminants and are currently attracting considerable concern due to their risks to plants, animals, and public health. Determining the vital environmental factors that affect the toxicity of target pollutants in soil is important for vegetable production and the maintenance and control of soil productivity. We investigated the influence of di-n-butyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) under different soil conditions on physiological changes in water spinach (Ipomoea aquatic Forsk.) seedlings and the rhizosphere soil microbial community. Supported by our former experiments in which we determined the representative concentrations that caused the most pronounced toxic effects, three experimental concentrations were studied including control soils without PAEs and spiked soils with either 20 mg DBP or DEHP kg-1 soil. The soil at all the three PAE concentrations was then adjusted to test two soil pH values, three levels of soil organic matter (SOM) content, and three levels of soil moisture content; thus, we completed 12 treatments or conditions simulating different soil environment conditions in greenhouses. After 30 days of cultivation, we analyzed the toxicity effects of two target PAEs on plant growth and physiological factors, and on soil microbial community characteristics. The toxicity of soil DBP and DEHP to the physiology of water spinach was found to be most affected by the soil pH value, then by SOM content, and least of all by soil moisture. The results of the 454 high-throughput sequencing analysis of the soil microbial community indicated that the toxicity of target PAEs to soil microorganisms was most affected by SOM content and then by soil moisture, and no clear relationship was found with soil pH. Under different soil conditions, declines in leaf biomass, chlorophyll a content, and carotenoid content-as well as increases in free amino acid (FAA) content, superoxide anion free radical activity, and hydroxyl radical activity-occurred in response to DBP or DEHP. Heavy use of chemical fertilizer, organic fertilizer, and high humidity led to the special environmental conditions of greenhouse soil, constituting the main conditions considered in this study. The results indicate that under the special highly intensive production systems of greenhouses, soil conditions may directly influence the effects of pollutant phytotoxicity and may thus endanger the yield, nutrient content, and food safety of vegetables. The combined studies of the impacts on plants and rhizosphere microorganisms give a more detailed picture of the toxic effects of the pollutants under different soil conditions.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31394816

RESUMO

The contamination status and the potential carcinogenic and non-carcinogenic health risks from six phthalate esters (PAEs), nominated as priority pollutants by the United States Environmental Protection Agency (USEPA), were investigated in 40 typical greenhouses in three large-scale intensive greenhouse production areas in Jingmen city, Hubei province, central China. The total concentrations of PAEs in 40 soil samples and 80 vegetable samples ranged from 919 ± 134 to 7015 ± 475 µg kg-1 (dry weight, DW), and from 387 ± 63, to 11,683 ± 1313 µg kg-1 (DW), respectively. No carcinogenic risk was detected. The heat-map of the hazard quotient (HQ) values indicates the non-carcinogenic risks to children from di-n-butyl phthalate (DBP), at two sampling sites out of the 40, and from diethylhexyl phthalate (DEHP) (20 to young children and three to older children and adults) at 23 of the sites. The contamination risk from PAEs at Pengdun is of concern because only two of the 14 sampling sites selected there showed the non-carcinogenic risk to humans was unclear. The results of this study help to close a long-term knowledge gap resulting from a shortage of experimental data on PAE contamination in intensive greenhouse vegetable production in central China. The inclusion of DEHP in the Chinese list of priority pollutants is recommended, due to its increasing contamination and risk. This study provides valuable information for protected agricultural soil management and risk avoidance. It is a timely reminder to take PAE contamination and associated health risks into consideration, during the planning and introduction of intensively-managed greenhouse production systems.

8.
Oncogene ; 38(42): 6850-6866, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31406252

RESUMO

Increasing evidence has indicated that circular RNAs (circRNAs) play a critical role in cancer development. However, only a small number of circRNAs have been experimentally validated and functionally annotated. In this study, using a high-throughput microarray assay, we identified a novel circRNA, circKDM4C, which was downregulated in breast cancer tissues with metastasis. Furthermore, we analyzed a cohort of breast cancer patients and found that circKDM4C expression was decreased in breast cancer tissues, and lower circKDM4C expression was associated with poor prognosis and metastasis in breast cancer. Functionally, we demonstrated that circKDM4C significantly repressed breast cancer proliferation, metastasis, and doxorubicin resistance in vitro and in vivo. Mechanistically, using a dual-luciferase activity assay and AGO2 RNA immunoprecipitation, circKDM4C was identified as a miR-548p sponge. We also found that PBLD was a direct target of miR-548p, which functioned as a tumor suppressor in breast cancer. Moreover, miR-548p overexpression was able to reverse the circKDM4C-induced attenuation of malignant phenotypes and elevated expression of PBLD in breast cancer cells. Taken together, our data indicate that circKDM4C might have considerable potential as a prognostic biomarker in breast cancer, and support the notion that therapeutic targeting of circKDM4C/miR-548p/PBLD axis may be a promising treatment approach for breast cancer patients.

9.
Food Funct ; 10(8): 5239, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31355835

RESUMO

Correction for 'Comparison of the nutritional properties and biological activities of kiwifruit (Actinidia) and their different forms of products: towards making kiwifruit more nutritious and functional' by Tingting Ma et al., Food Funct., 2019, 10, 1317-1329.

10.
J Exp Clin Cancer Res ; 38(1): 310, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307515

RESUMO

BACKGROUND: Exosomes from cancer cells or immune cells, carrying bio-macromolecules or microRNAs (miRNAs), participate in tumor pathogenesis and progression by modulating microenvironment. Our study aims to investigate the role of these microRNA-501-3p (miR-501-3p) containing exosomes derived from tumor-associated macrophage (TAM) in the progression of pancreatic ductal adenocarcinoma (PDAC). METHODS: Firstly, the function of TAM recruitment in PDAC tissues was assessed, followed by identification of the effects of M2 macrophage-derived exosomes on PDAC cell activities and tumor formation and metastasis in mice. In silico analysis was conducted to predict differentially expressed genes and regulatory miRNAs related to PDAC treated with macrophages, which determined miR-501-3p and TGFBR3 for subsequent experiments. Next, gain- and loss-of-function experiments were performed to examine their role in PDAC progression with the involvement of the TGF-ß signaling pathway. RESULTS: TAM recruitment in PDAC tissues was associated with metastasis. Highly expressed miR-501-3p was observed in PDAC tissues and TAM-derived exosomes. Both M2 macrophage-derived exosomes and miR-501-3p promoted PDAC cell migration and invasion, as well as tumor formation and metastasis in nude mice. MiR-501-3p was verified to target TGFBR3. PDAC cells presented with down-regulated TGFBR3, which was further decreased in response to M2 macrophage treatment. TGF-ß signaling pathway activation was implicated in the promotion of miR-501-3p in PDAC development. The suppression of macrophage-derived exosomal miR-501-3p resulted in the inhibition of tumor formation and metastasis in vivo. CONCLUSION: M2 macrophage-derived exosomal miR-501-3p inhibits tumor suppressor TGFBR3 gene and facilitates the development of PDAC by activating the TGF-ß signaling pathway, which provides novel targets for the molecular treatment of PDAC.

11.
Trials ; 20(1): 419, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291976

RESUMO

BACKGROUND: Stroke is characterized by high morbidity, high mortality, and high disability. Spasticity, one of the most common complications after stroke, may reduce the potential success of rehabilitation and has a detrimental effect on stroke patients' daily function and quality of life. Moreover, the long-term management of spasticity is a financial burden to patients and increases societal costs. The current treatments, mainly including physical therapy, oral drugs, drug injection therapy, and surgical interventions, have been used to reduce spasticity. However, every conventional approach has its limitations. Acupuncture at the "Wang's Jiaji" acupoints, based on the experience of the famous old doctor of traditional Chinese medicine (TCM) Le Ting Wang in treating post-stroke limb spasm, has been widely practiced in our department. This intervention has effectively avoided the controversy around acupuncture at local acupoints on the limbs, and is easy to apply without side effects. Our previous studies had found that acupuncture at the "Wang's Jiaji-points" can reduce the occurrence and severity of spasticity occurring after stroke in the early stage (the first 21 days). In this study, we chose patients in the convalescent stage, 1-6 months after stroke, so as to study the efficacy and the specific intervention time of "Wang's jiaji" in the convalescent stage after stroke. METHODS: This is a randomized, controlled, and single-blind study. Patients in the convalescent stage within 1-6 months of ischemic stroke will be selected as subjects. A total of 100 subjects will be randomly assigned to two groups. The acupuncture group will be given acupuncture treatment five times a week; the medicine group will be given 10mg baclofen three times a day. These two groups will continue to receive current usual care for the prevention and treatment of cerebrovascular diseases, but drugs that affect muscle tone will not be allowed. The treatment will last for 2 weeks. The primary outcome measurement is the simplified Fugl-Meyer Assessment. The secondary outcome measurements are the Modified Ashworth Scale, Modified Barthel Scale, and the H-reflex, F response, and H/M ratios of electromyography. All outcome measurements are assessed at baseline, 2 weeks, 4 weeks, and 12 weeks after first treatment except the electromyography, which is assessed at baseline and 2 weeks after first acupuncture. DISCUSSION: This trial aims to evaluate the effects and the specific intervention time of "Wang's Jiaji" acupoints on spasticity after stroke. TRIAL REGISTRATION: ISRCTN registry, ISRCTN31511176 . Registered on 29 August 2017. Version number of protocol 2016-2-1161 Version date of protocol: 2016-1.

12.
Hematol Oncol ; 37(4): 456-463, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31348835

RESUMO

To illustrate the clinical and genetic features of elderly and secondary acute myeloid leukemia (AML) patients, we compared 145 elderly AML (e-AML) and 55 secondary AML (s-AML) patients with 451 young de novo AML patients. Both e-AML and s-AML patients showed lower white blood cell (WBC) and bone marrow (BM) blasts at diagnosis. NPM1, DNMT3A, and IDH2 mutations were more common while biallelic CEBPA and IDH1 mutations were less seen in e-AML patients. s-AML patients carried a higher frequency of KMT2A-AF9. In treatment response and survival, e/s-AML conferred a lower complete remission (CR) rate and shorter duration of event-free survival (EFS) and overall survival (OS) compared with young patients. In multivariate analysis, s-AML was an independent risk factor for OS but not EFS in the whole cohort. Importantly, intensive therapy tended to improve the survival of e/s-AML patients without increasing the risk of early death, and hematopoietic stem cell transplantation (HSCT) could rescue the prognosis of s-AML, which should be recommended for the treatment of fit patients.


Assuntos
Leucemia Mieloide Aguda/genética , Segunda Neoplasia Primária/genética , Adolescente , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Aberrações Cromossômicas , Feminino , Genes Neoplásicos , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasia Residual , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Células-Tronco Neoplásicas/patologia , Prognóstico , Intervalo Livre de Progressão , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
14.
Mol Ther Nucleic Acids ; 17: 347-361, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31302495

RESUMO

Emerging evidence suggests that circular RNAs (circRNAs) have crucial roles in various processes, including cancer development and progression. However, the functional roles of circRNAs in breast cancer remain to be elucidated. In this study, we identified a novel circRNA (named circBMPR2) whose expression was lower in breast cancer tissues with metastasis. Moreover, circBMPR2 expression was negatively associated with the motility of breast cancer cells and significantly downregulated in human breast cancer tissues. Functionally, we found that circBMPR2 knockdown effectively enhanced cell proliferation, migration, and invasion. Moreover, circBMPR2 knockdown promoted tamoxifen resistance of breast cancer cells through inhibiting tamoxifen-induced apoptosis, whereas circBMPR2 overexpression led to decreased tamoxifen resistance. Mechanistically, we demonstrated that circBMPR2 could abundantly sponge miR-553 and that miR-553 overexpression could attenuate the inhibitory effects caused by circBMPR2 overexpression. We also found that ubiquitin-specific protease 4 (USP4) was a direct target of miR-553, which functions as a tumor suppressor in breast cancer. Our findings demonstrated that circBMPR2 might function as a miR-553 sponge and then relieve the suppression of USP4 to inhibit the progression and tamoxifen resistance of breast cancer. Targeting this newly identified circRNA may help us to develop potential novel therapies for breast cancer patients.

15.
Surg Oncol ; 29: 48-52, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31196493

RESUMO

BACKGROUND AND OBJECTIVES: Latissimus dorsi, an anatomical landmark for axillary lymph node dissection, was reported to harbor an anatomical variation named Langer's axillary arch (LAA). However, the incidence and clinical significance of LAA in breast cancer remain obscure. METHODS: We conducted a six-year prospective study, including 1724 breast cancer patients in Qilu hospital between January 2012 to February 2018. All patients received ALND were inspected for existence of LAA. All the surgeries were completed with the involvement of same experienced surgeon. Once the LAA was identified, all the lymph nodes located lateral to it, named LAA's lymph node, were dissected and collected for pathologic examination. RESULTS: Among 1724 breast cancer patients, LAA was identified in 132 patients (7.66%). 120 out of the 132 patients (90.91%) had at least two LAA's lymph nodes. 21 out of 120 patients (17.50%) were confirmed with cancer cell metastasis in LAA's lymph nodes. Among the 23 patients received sentinel lymph node tracing, sentinel lymph node was located lateral to LAA in 3 patients (13.04%). CONCLUSIONS: Our results indicated that it is of great importance for surgeons to correctly ascertain LAA, and it should be taken as a nonnegligible parts during ALND or SLNB.

16.
Anal Chim Acta ; 1075: 38-48, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31196422

RESUMO

Gas chromatography inductively coupled plasma triple quadrupole mass spectrometry (GC-ICP-MS/MS) operated in N2O reaction mode (mass-shift mode) was established for the analysis of six congeners of polybrominated diphenyl ethers (PBDEs): BDE 28, BDE 47, BDE 99, BDE 100, BDE 153 and BDE 154 in fish samples. The spectral interference on the determination of PBDEs was eliminated by measuring the product ion (BrO+) instead of traditional methods measuring Br+. After comparing the signal intensities of the three reaction gases (O2, H2, and N2O), the highest sensitivity was found using N2O as the reaction gas. The results showed that bromine is an element that suffers from strong spectral overlap in ICP, mainly from Ar-based polyatomic interferences. Spectral interference was assessed by measuring the bromine isotope ratio of 81Br+ and 79Br+ of the six priority PBDEs in the He collision mode and N2O reaction mode, respectively. In the conventional He collision mode, the relative isotope ratio of 79Br/81Br (the measured isotope ratio to the natural isotope ratio) of the analytes ranged from 0.955 to 0.965, which proves that using He as the collision gas cannot completely eliminate the spectral interference. In the N2O reaction mode, the relative isotope ratio of 79Br/81Br ranged from 0.991 to 1.004, demonstrating that spectral interference can be fully eliminated. Samples were processed using the modified QuEChERs method with detection limits ranging from 0.03 to 0.09 ng g-1 with a relative standard deviation of less than 3%. Six priority PBDEs in the NIST reference materials SRM 1947 (frozen fish tissue homogenate) were determined by mass-shift mode to verify this conclusion. No statistically significant difference was observed between the measured value and the certified value, with recoveries between 95% and 114%. The method was applied to the analysis of PBDEs in marine fish samples and five PBDEs were observed (BDE28,BDE-47, BDE-99, BDE-100 and BDE-153) at concentrations ranging from 0.04 to 0.54 ng g-1.


Assuntos
Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Animais , Peixes , Cromatografia Gasosa-Espectrometria de Massas/métodos , Limite de Detecção , Espectrometria de Massas em Tandem/métodos
19.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(3): 295-298, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31218865

RESUMO

OBJECTIVE: To observe the clinical outcomes of a combined unilateral intraoral and extraoral reduction approach in the treatment of anterior temporomandibular joint (TMJ) dislocation. METHODS: Postural muscular chains were utilized in the biomechanical analysis of stomatognathic systems for improving TMJ repositioning approaches. A total of 87 patients with anterior TMJ dislocation were included in the present study. A combined unilateral intraoral and extraoral reduction approach was applied, and the clinical effects were evaluated. RESULTS: Biomechanical analysis reveal that reflexive contrac-tion of the maxillary muscle group was blocked sufficiently during the combined unilateral intraoral and extraoral reduction process. All dislocated TMJs were set successfully and efficiently with few complications. CONCLUSIONS: Combined unilateral intraoral and extraoral reduction approach is an effective, convenient, and minimally invasive way to treat anterior TMJ dislo-cations.


Assuntos
Luxações Articulares , Procedimentos Cirúrgicos Reconstrutivos , Transtornos da Articulação Temporomandibular , Humanos , Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/cirurgia
20.
Phytomedicine ; 58: 152745, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31005715

RESUMO

BACKGROUND: Rare ginsenosides are found in ginseng and notoginseng, two medicinal plants widely used in China for treatment of cardiovascular diseases and type 2 diabetes. However, their pharmacological studies regarding myocardial fuel metabolism and insulin signaling are not clear. PURPOSE: To explore the effect of a rare ginsenoside-standardized extract (RGSE), derived from steamed notoginseng, on cardiac fuel metabolism and insulin signaling. STUDY DESIGN: We used palmitic acid (PA) to treat H9c2 cells in vitro and high fat diet (HFD) to mice to induce insulin resistance in vivo. METHODS: In vitro, differentiated H9c2 cells were pretreated with RGSE, metformin, mildronate or dichloroacetate (DCA) and stimulated with PA. In vivo, mice were fed with HFD and received RGSE, metformin or DCA for 6 weeks. Protein expression was determined by Western blotting. Mitochondrial membrane potential (Δψm), glucose uptake and reactive oxygen species (ROS) production were measured by fluorescence labeling. Other assessments including oxygen consumption rate (OCR) were also performed. RESULTS: RGSE prevented PA-induced decrease in pyruvate dehydrogenase (PDH) activity and increase in carnitine palmitoyltransferase 1 (CPT1) expression, and ameliorated insulin-mediated glucose uptake and utilization in H9c2 cells. Metformin and mildronate exhibited similar effects. In vivo, RGSE counteracted HFD-induced increase in myocardial expression of p-PDH and CPT1 and ameliorated cardiac insulin signaling. Metformin and DCA also showed beneficial effects. Further study showed that RGSE decreased OCR and mitochondrial complex I activity in PA-treated H9c2 cells, reduced ROS production and relieved mitochondrial oxidative stress, thus decreased serine phosphorylation in IRS-1. CONCLUSION: RGSE ameliorated myocardial insulin sensitivity under conditions of lipid overload, which was tightly associated with the decrease in mitochondrial oxidative stress via modulating glucose and fatty acid oxidation.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Ginsenosídeos/farmacologia , Coração/efeitos dos fármacos , Resistência à Insulina , Animais , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular , Glucose/metabolismo , Insulina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Miocárdio/citologia , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Panax notoginseng/química , Complexo Piruvato Desidrogenase/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
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