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1.
Chem Biodivers ; 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32249503

RESUMO

The present study investigated the allelopathic effects of aqueous extracts of Castanea henryi litter on the growth and physiological responses of Brassica pekinensis and Zea mays. Treatment with high concentrations of leaf extract (0.05 g/ml for B. pekinensis and 0.10 g/ml for Z. mays) significantly increased malonaldehyde content and reduced seed germination, seedling growth, chlorophyll content, and the activity levels of antioxidant enzymes. These effects generally increased with increasing extract concentration. However, in Z. mays, low extract concentrations actually promoted seed germination, shoot growth, chlorophyll content, and antioxidant enzyme activity. The allelopathic effects of the various C. henryi extracts decreased as follows: leaf extract > twig extract > shell extract. Eleven potential allelochemicals including rutin, quercetin, luteolin, procyanidin A2, kaempferol, allantoin, propionic acid, salicylic acid, jasmonic acid, methylmalonic acid, and gentisic acid were identified in the leaves of C. henryi which were linked to the strongest allelopathic effects. These findings suggest that the allelopathic effects of C. henryi differ depending on receptor plant species, and that leaves are the most allelopathic litter in C. henryi.

2.
J Cell Mol Med ; 24(9): 5224-5237, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32233073

RESUMO

Liver fibrosis, a consequence of unhealthy modern lifestyles, has a growing impact on human health, particularly in developed countries. Here, we have explored the anti-fibrotic effects of propylene glycol alginate sodium sulphate (PSS), a natural extract from brown algae, in fibrotic mice and cell models. Thus, we established bile duct ligature and carbon tetrachloride mouse models and LX-2 cell models with or without PSS treatment. Liver pathological sections and the relevant indicators in serum and liver tissues were examined. PSS prevented hepatic injury and fibrosis to a significant extent, and induced up-regulation of matrix metalloproteinase-2 and down-regulation of tissue inhibitor of metalloproteinase-1 through suppressing the transforming growth factor ß1 (TGF-ß1)/Smad pathway. PSS additionally exerted an anti-autophagy effect through suppressing the Janus kinase (JAK) 2/transducer and activator of transcription 3 (STAT3) pathway. In conclusion, PSS prevents hepatic fibrosis by suppressing inflammation, promoting extracellular matrix (ECM) decomposition and inactivating hepatic stellate cells through mechanisms involving the TGF-ß1/Smad2/3 and JAK2/STAT3 pathways in vivo and in vitro.

3.
Methods Appl Fluoresc ; 8(2): 025008, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32150730

RESUMO

Single molecule localization microscopy (SMLM) allows the imaging of cellular structures with resolutions five to ten times below the diffraction limit of optical microscopy. It was originally introduced as a two-dimensional technique based on the localization of single emitters as projection onto the x-y imaging plane. The determination of the axial position of a fluorescent emitter is only possible by additional information. Here we report a method (spatial filter SMLM (SFSMLM)) that allows to determine the axial positions of fluorescent molecules and nanoparticles on the nanometer scale by the usage of two spatial filters, which are placed in two otherwise identical emission detection channels. SFSMLM allows axial localization in a range of ca. 1.5 µm with a localization precision of 15 - 30 nm in axial direction. The technique was utilized for localizing and imaging small cellular structures - e.g. actin filaments, vesicles and mitochondria - in three dimensions.

4.
J Hepatocell Carcinoma ; 7: 19-31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110554

RESUMO

Objective: Shikonin is a natural product with many activities, including anti-cancer effects. Pyruvate kinase type M2 (PKM2) plays a crucial role in the growth of tumor cells. However, the effect of shikonin on PKM2 in hepatocellular carcinoma (HCC) is unclear. Methods: Cell viability, apoptosis level, glucose uptake, and lactate production were detected in HCC cells. Lentivirus-overexpressed and -shRNA of PKM2 were used to verify the key target of shikonin. A xenograft mouse model was used to detect the efficacy of shikonin and its combination with sorafenib in vivo. Results: Shikonin inhibited proliferation and glycolysis and induced apoptosis in HCC cells. Either PKM2-overexpressed or PKM2-shRNA alleviated or enhanced this effect. The results of CCK-8 showed that shikonin significantly inhibited cell viability of HCC cells. The levels of glucose uptake and lactate production were dramatically decreased by shikonin-treated. Results of flow cytometry and Western blot showed that the levels of apoptosis of HCC cells were significantly increased in a dose-dependent manner after shikonin treatment. In addition, shikonin enhanced the anti-cancer effect of sorafenib in vitro and in vivo. Our results showed that SK combined with sorafenib markedly inhibits tumor growth in HCC-transplanted nude mice compared to SK or sorafenib alone. Conclusion: By inhibiting PKM2, shikonin inhibited proliferation and glycolysis and induced cell apoptosis in HCC cells. The effect of shikonin on tumor cell proliferation, apoptosis and glycolsis will make it promising drug for HCC patients.

5.
Front Pharmacol ; 10: 1248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708778

RESUMO

Eupafolin is the main bioactive component extracted from the traditional Chinese medicine Ay Tsao (Artemisia vulgaris L.), and its anti-tumor activity has had been studied in previous researches. T-LAK cell-originated protein kinase (TOPK) belongs to serine/threonine protein kinase and is highly expressed in several cancer cells and tissues, such as colon cancer, lung cancer, esophagus cancer, and so on. Therefore, it was recognized as an important target for treating tumors. Nowadays, we found that eupafolin suppressed TOPK activities at the first time in vitro and in vivo. The cells study indicated that eupafolin suppressed TOPK activities in JB6 Cl41 and KYSE450 cells. Furthermore, knockdown of TOPK in KYSE450 cells decreased their sensitivities to eupafolin. The animal study showed that the injection of eupafolin in patient-derived xenograft (PDX) mouse effectively suppressed tumor growth. Histone H3 and Ki67 were reduced, and cleaved caspase 3 was increased in tumor tissues after eupafolin treatment. To sum up, eupafolin as an TOPK inhibitor can suppress growth of esophagus cancer in vitro and in vivo. The TOPK downstream signaling molecule histone H3 in tumor tissues was also reduced after eupafolin treatment. In short, eupafolin can suppress growth of esophagus cancer cells as an TOPK inhibitor both in vitro and in vivo.

6.
J Cell Mol Med ; 23(9): 6479-6493, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328391

RESUMO

BACKGROUND: Liver fibrosis is a wound-healing process of liver featured by the over-deposition of extracellular matrix (ECM) and angiogenesis. However, the effective treatment is lacking. Procyanidin B2 (PB2) is a flavonoid extract abundant in grape seeds with anti-oxidant, anti-inflammatory and anti-cancer properties. The present study aimed to determine effects of PB2 on liver fibrosis. METHOD: The CCl4-induced mouse liver fibrosis model and a human hepatic stellate cell (HSC) line (LX2 cells) were used to study the activation, ECM production and angiogenesis of HSCs through Western blotting analysis, immunohistochemistry, immunofluorescence staining, flow cytometry and tubulogenesis assay. A Hedgehog (Hh) pathway inhibitor (cyclopamine) and Smoothened agonist (SAG) were used to investigate the role of PB2 on Hh pathway. RESULTS: The results showed that PB2 could inhibit the proliferation and induce apoptosis of HSCs. PB2 could also down-regulate the expressions of VEGF-A, HIF-1α, α-SMA, Col-1 and TGF-ß1 of HSCs in vivo and in vitro. The application of SAG and cyclopamine proved that PB2 targets on Hh pathway. CONCLUSIONS: PB2 inhibited the Hh pathway to suppress the activation, ECM production and angiogenesis of HSCs, therefore reverses the progression of liver fibrosis in vivo and in vitro.

7.
Mediators Inflamm ; 2019: 3240713, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316298

RESUMO

Hepatic ischemia reperfusion (IR) injury (IRI) occurs during liver transplantation, hepatectomy, and hemorrhagic shock. Oleanolic acid (OA) is a natural compound with antioxidant and anti-inflammatory activity that has been used to treat liver disorders in clinical practice for several years. Here, we investigated the effects and underlying mechanisms of OA in hepatic IRI. A 60-minute partial (70%) hepatic, warm, ischemic reperfusion model was established in BALB/c mice, and two doses (30 and 60 mg/kg) of OA were administered intragastrically for 7 consecutive days prior to hepatic IR. Orbital blood and liver specimens were collected at 2, 8, and 24 h after IR. The results showed that OA preconditioning significantly alleviated hepatic injury, as evidenced by decreased alanine aminotransferase and aspartate aminotransferase levels; improved histology, inhibition of JNK phosphorylation, and high mobility group box 1 (HMGB1); and tumor necrosis factor-α downregulation in hepatic IR mice. OA upregulated Bcl-2 and downregulated caspase-3, caspase-9, Bax, Beclin 1, and LC3, which play crucial roles in the regulation of apoptosis and autophagy. These findings highlighted the protective effects of OA against hepatic IRI mediated by the inhibition of apoptosis and autophagy and the release of HMGB1, which acted as a late inflammatory mediator in hepatic IRI.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína HMGB1/metabolismo , Ácido Oleanólico/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Hepatectomia , Inflamação , Fígado/patologia , Transplante de Fígado , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Transdução de Sinais , Condicionamento Pré-Transplante , Fator de Necrose Tumoral alfa/metabolismo
8.
Cancer Med ; 8(10): 4806-4820, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31273958

RESUMO

OBJECTIVE: Hepatocellular carcinima is one of the most common tumors in clinic and also one of the leading causes of death from cancer worldwide. Quercetin shows significant effects on blocking the development of various cancers. METHODS: We used the human hepatocellular carcinoma LM3 and nude mice tumor model to assess the effects of quercetin in hepatocellular carcinoma and clarify its mechanism of action. We collected LM3 cell line treated with different doses of quercetin at different time periods and determined the vital indexes. The liver tissues of mice were collected and used for western boltting (WB), Hematoxylin and Eosin (H&E) and TUNEL staining. RESULTS: Results indicated that quercetin suppressed the Hepatocellular carcinoma (HCC) growth both in vivo and in vitro. Quercetin could disturb LM3 cells proliferation and cell cycle distribution, thus inducing apoptosis. At the same time, quercetin inhibited LM3 cells migration and invasion and promoted HCC autophagy. These effects at least partly depended on the down-regulation of the activation of JAK2 and STAT3 by quercetin. CONCLUSION: Quercetin inhibited hepatocellular carcinoma progression by modulating cell apoptosis, migration, invasion, and autophagy; and its effects were at least partly related with the JAK2/STAT3 signaling pathway.

9.
Theranostics ; 9(6): 1580-1598, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037125

RESUMO

Effective delivery is the primary barrier against the clinical translation of gene therapy. Yet there remains too much unknown in the gene delivery mechanisms, even for the most investigated polymeric carrier (i.e., PEI). As a consequence, the conflicting results have been often seen in the literature due to the large variability in the experimental conditions and operations. Therefore, some key parameters should be identified and thus strictly controlled in the formulation process. Methods: The effect of the formulation processing parameters (e.g., concentration or mixture volume) and the resulting nanostructure properties on gene transfection have been rarely investigated. Two types of the PEI/DNA nanoparticles (NPs) were prepared in the same manner with the same dose but at different concentrations. The microstructure of the NPs and the transfection mechanisms were investigated through various microscopic methods. The therapeutic efficacy of the NPs was demonstrated in the cervical subcutaneous xenograft and peritoneal metastasis mouse models. Results: The high-concentration process (i.e., small reaction-volume) for mixture resulted in the large-sized PEI/DNA NPs that had a higher efficiency of gene transfection, compared to the small counterpart that was prepared at a low concentration. The microstructural experiments showed that the prepared small NPs were firmly condensed, whereas the large NPs were bulky and botryoid-shaped. The large NPs entered the tumor cells via the macropinocytosis pathway, and then efficiently dissociated in the cytoplasm and released DNA, thus promoting the intranuclear delivery. The enhanced in vivo therapeutic efficacy of the large NPs was demonstrated, indicating the promise for local-regional administration. Conclusion: This work provides better understanding of the effect of formulation process on nano-structural properties and gene transfection, laying a theoretical basis for rational design of the experimental process.

10.
Onco Targets Ther ; 12: 2623-2633, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114221

RESUMO

Background: Increasing evidence has identified circular RNAs (circRNAs) as ideal molecular biomarkers for cancer diagnosis, therapy, and prognosis. However, the overall diagnostic efficiency of circRNAs remains unclear. Thus, this meta-analysis aimed to comprehensively evaluate the diagnostic accuracy of circRNA expression profiles for cancer. Methods: A literature search of online databases was conducted to identify all eligible studies. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All statistical analyses were executed using STATA 14.0, Meta-DiSc 1.4, and Review Manager 5.2 software. Results: A total of 32 studies, involving 2,400 cases and 2,295 controls, were included in the diagnostic meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve were 0.79 (95% CI: 0.73-0.84), 0.73 (95% CI: 0.67-0.79), 2.9 (95% CI: 2.5-3.5), 0.29 (95% CI: 0.24-0.36), 10 (95% CI: 8-13), and 0.83 (95% CI: 0.79-0.86), respectively. The overall analysis suggested that circRNAs are useful diagnostic biomarkers for cancer. Subgroup analysis indicated that plasma samples had a better diagnostic performance than cancer tissue samples for cancer detection. Studies involving ≥100 cases or gastric cancer showed higher sensitivities than those including <100 cases or other cancers. Conclusion: This meta-analysis revealed that circRNAs were significantly correlated with cancer diagnosis. In addition, circRNAs had good diagnostic accuracy and might serve as effective diagnostic biomarkers for cancer.

11.
Polymers (Basel) ; 11(3)2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30960371

RESUMO

A coupled diffusion model based on continuum thermodynamics is developed to quantitatively describe the transport properties of glassy thin films during physical aging. The coupled field equations are then embodied and applied to simulate the transport behaviors of O2 and CO2 within aging polymeric membranes to validate the model and demonstrate the coupling phenomenon, respectively. It is found that due to the introduction of the concentration gradient, the proposed direct calculating method on permeability can produce relatively better consistency with the experimental results for various film thicknesses. In addition, by assuming that the free volume induced by lattice contraction is renewed upon CO2 exposure, the experimental permeability of O2 within Matrimid® thin film after short-time exposure to CO2 is well reproduced in this work. Remarkably, with the help of the validated straightforward permeability calculation method and free volume recovery mechanism, the permeability behavior of CO2 is also well elucidated, with the results implying that the transport process of CO2 and the variation of free volume are strongly coupled.

12.
Eur J Pharmacol ; 854: 247-255, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31002778

RESUMO

Ginsenoside Rg1 is the active ingredient of Chinese herbal medicine ginseng and sanqi, which has remarkable effects on anti-inflammation and anti-diabetes. In this study, we explored the molecular mechanism of ginsenoside Rg1 against diabetes in rat subjected to insulin resistance induced by high-fat and high-sugar (HFHS). Biochemical analysis revealed that ginsenoside Rg1 significantly decreased the serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, total cholesterol, triglyceride, low-density lipoprotein and increased the serum levels of high-density lipoprotein, which indicated ginsenoside Rg1 improved the extent of hepatic steatosis. Furthermore, ginsenoside Rg1 suppressed the expression of IL-1ß, IL-6,TNF-α,NF-κB and G6Pase, however, p-Akt was up-regulated. These results suggested that ginsenosideRg1 improved insulin resistance through suppressing inflammatory response and glucose output, which may be a potential therapeutic strategy in protecting hepatic steatosis.


Assuntos
Gorduras na Dieta/efeitos adversos , Açúcares da Dieta/efeitos adversos , Ginsenosídeos/farmacologia , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/uso terapêutico , Glucose-6-Fosfatase/genética , Inflamação/tratamento farmacológico , Proteínas Substratos do Receptor de Insulina/genética , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
13.
Front Genet ; 10: 316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31024626

RESUMO

Tung tree (Vernicia fordii), an economically important woody oil plant, is a monoecious and diclinous species with male and female flowers on the same inflorescence. The extremely low proportion of female flowers leads to low fruit yield in tung orchards. The female flower normally develops along with stamen abortion; otherwise sterile ovules will be produced. However, little knowledge is known about the molecular basis of the female flower development in tung tree. In this study, integrated analyses of morphological and cytological observations, endogenous phytohormone assay and RNA-seq were conducted to understand the molecular mechanism of the female flower development in tung tree. Cytological observation suggested that the abortion of stamens in female flowers (SFFs) belongs to the type of programmed cell death (PCD), which was caused by tapetum degeneration at microspore mother cell stage. A total of 1,366 differentially expressed genes (DEGs) were identified in female flowers by RNA-seq analysis, of which 279 (20.42%) DEGs were significantly enriched in phenylpropanoid biosynthesis, phenylalanine metabolism, flavonoid biosynthesis, starch and sucrose metabolism, and plant hormone signal transduction. Stage-specific transcript identification detected dynamically expressed genes of important transcription regulators in female flowers that may be involved in PCD and floral organ development. Gene expression patterns revealed that 17 anther and pollen development genes and 37 PCD-related genes might be involved in the abortion of SFF. Further analyses of phytohormone levels and co-expression networks suggested that salicylic acid (SA) accumulation could trigger PCD and inhibit the development of SFF in tung tree. This study provides new insights into the role of SA in regulating the abortion of SFF to develop normal female flowers.

14.
Sci Rep ; 9(1): 4085, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30858470

RESUMO

The rapid increase in use of electronic-cigarettes (e-cigarettes), especially among youth, raises the urgency for regulating bodies to make informed decisions, guidance, and policy on these products. This study evaluated cardiac function in an experimental model following exposure to e-cigarettes. We subjected C57BL/6 mice to e-cigarette vaping for 2-weeks, and cardiac function was assessed using echocardiography. Cardiac tissues were collected at the end of e-cigarette exposure for pathological analysis. The experimental data showed that e-cigarette vaping (3 h/day for 14 days) had no significant effect on cardiac contractility as measured by ejection fraction. However, it significantly increased angiogenesis in mouse heart tissue. We found that e-cigarette exposure increased the endothelial cell marker CD31 and CD34 to approximately 2 fold (p < 0.05) in heart tissue from female mice and about 150% (p < 0.05) in male mice. E-cigarette vaping also caused slower weight gain compared to mice exposed to room air. In addition, short-term e-cigarette exposure slightly increased collagen content in heart tissue but did not result in significant tissue fibrosis. These results suggest that short-term exposure to e-cigarettes has no acute effect on cardiac contractile function or tissue fibrosis, but it increases cardiac angiogenesis.

15.
Int Immunopharmacol ; 70: 435-445, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30856394

RESUMO

BACKGROUND: Hepatic ischemia/reperfusion (IR) injury is a common medical phenomenon that occurs during a number of clinical conditions, such as liver transplantation, severe injuries, and shock. In our study, we determined the protective functions of levo-tetrahydropalmatine (L-THP) on hepatic IR injury in mice by inhibiting the ERK/NF-κB signaling pathway. METHOD: BALB/c mice were randomly divided into six groups as follows: normal control (NC); sham; L-THP (40 mg/kg); IR; L-THP (20 mg/kg) + IR; and L-THP (40 mg/kg) + IR. Liver tissues and sera were collected at three time points after reperfusion (2, 8, and 24 h). The liver enzyme, inflammatory factor, and other protein levels in the serum and liver tissues were detected. RESULTS: L-THP pretreatment alleviated hepatocyte injury caused by IR and reduced the production of proinflammatory cytokines, such as IL-6 and TNF-α. Furthermore, L-THP could inhibit the ERK/NF-κB signaling pathway to attenuate hepatocyte apoptosis and autophagy. And the protective effect of L-THP is positively correlated with its dose. CONCLUSION: L-THP protects the liver from IR injury by inhibiting the release of inflammatory factors and alleviating liver cell apoptosis and autophagy. The protective functions of L-THP may be partly based on the downregulation of the ERK/NF-κB pathway.


Assuntos
Anti-Inflamatórios/uso terapêutico , Alcaloides de Berberina/uso terapêutico , Hepatócitos/efeitos dos fármacos , Fígado/fisiologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Células Cultivadas , Hepatócitos/fisiologia , Humanos , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
Cell Transplant ; 28(3): 306-317, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30700111

RESUMO

MicroRNA plays a pivotal role in various human cancers, especially in human gastric cancer. In the present study, we evaluated the effect of microRNA-21 (miR-21) on the gastric cancer cell proliferation, migration, apoptosis and the related signaling cascades. Here, we showed that down-regulation of miR-21 markedly reduced gastric cancer cell proliferation (AGS and NCI-N87 cells) in a time dependent manner. Moreover, our findings revealed that silencing miR-21 dramatically blocked gastric cancer cell migration and movement, which might be related to down-regulation of vimentin expression. We also found that down-regulation of miR-21 promoted cell apoptosis and repressed cell cycle progression. Further investigation showed that down-regulation of miR-21 significantly increased phosphatase and tensin homolog (PTEN) protein expression level, but not transcription level (mRNA level), which in turn decreased Akt phosphorylation at Thr308 and Ser473. Collectively, our results uncover that miR-21 targets PTEN/Akt signaling pathway and regulates cell proliferation, migration and apoptosis in human gastric cancer cells. Our findings may provide a therapeutic target for treatment of human gastric cancer.

17.
Eur J Pharmacol ; 843: 277-284, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30485790

RESUMO

Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes. The liver is an important organ responsible for the development of insulin resistance, and exploring liver glucose metabolism is important to study insulin resistance. We first established the model of insulin resistance in HepG2 cells and then treated them with different concentrations of ginsenoside-Rg1. The results showed that ginsenoside-Rg1 is not toxic to HepG2 cells. In addition, ginsenoside-Rg1 relieved the insulin-induced insulin resistance in HepG2 cells. Furthermore, ginsenoside-Rg1 increased the uptake of glucose by reducing reactive oxygen species and down-regulating the phosphorylation level of p38 MAPK. In addition, ginsenoside-Rg1 also decreased the output of glucose by increasing Akt phosphorylation and reducing GSK3ß expression. In conclusion, ginsenoside-Rg1 can alleviate the insulin resistance through increasing the uptake of glucose and decreasing the output of glucose.


Assuntos
Ginsenosídeos/farmacologia , Glucose/metabolismo , Células Hep G2 , Humanos , Resistência à Insulina , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
J Gastroenterol Hepatol ; 34(1): 263-276, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29864192

RESUMO

BACKGROUND AND AIM: Liver fibrosis is a worldwide clinical challenge during the progression of chronic liver disease to liver cirrhosis. Shikonin is extracted from the root of Lithospermum erythrorhizon with antioxidant, anti-inflammatory, anticancer, and wound-healing properties. The study aims to investigate the protective effect of shikonin on liver fibrosis and its underlying mechanism. METHODS: Two liver fibrosis models were established in male C57 mice by intraperitoneal injection of CCl4 or bile duct ligation. Shikonin was administered orally three times weekly at a dose of 2.5 or 5 mg/kg. Protein and mRNA expressions were assayed by quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemical staining. RESULTS: Shikonin significantly inhibited activation of hepatic stellate cells and extracellular matrix formation by downregulating the transforming growth factor-ß1 expression and maintaining the normal balance between metalloproteinase-2 and tissue inhibitor of metalloproteinase-1. Shikonin also decreased hepatic stellate cell energy production by inhibiting autophagy. CONCLUSIONS: The results confirmed that shikonin attenuated liver fibrosis by downregulating the transforming growth factor-ß1/Smads pathway and inhibiting autophagy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Naftoquinonas/farmacologia , Proteínas Smad Reguladas por Receptor/antagonistas & inibidores , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspartato Aminotransferases/sangue , Autofagia/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Matriz Extracelular/metabolismo , Células Estreladas do Fígado/fisiologia , Cirrose Hepática/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Naftoquinonas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-1/metabolismo
19.
Kaohsiung J Med Sci ; 34(10): 556-563, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30309483

RESUMO

This study aimed to investigate the expression of miRNA-21 during intestinal barrier dysfunction induced by intestinal ischemia reperfusion. Forty SPF SD rats were divided into 5 groups randomly. Intestinal ischemia-reperfusion injury (IRI) was induced by mesenteric artery occlusion for 1 h and reperfusion for 1 h, and the rats were sacrificed at 1, 3, 6 and 12 h after reperfusion. Fresh intestine tissues were immediately isolated for the measurement of transepithelial electrical resistance (TER). The levels of cytokines, ICAM-1, DAO, iFABP and MPO in serum were determined by ELISA. Intestinal tight junction proteins occludin and claudin-1 were detected by immunofluorescence analysis and Western blot analysis. miR-21 expression in intestinal tissues was measured by RT-PCR. Compared with sham group, the levels of pro-inflammatory cytokines TNF-α and IL-6 and ICAM-1, DAO, iFABP and MPO increased while IL-10 level decreased in intestinal ischemia-reperfusion group. In addition, the levels of intestinal tight junction proteins occludin and claudin-1 decreased while miR-21 level increased in intestinal ischemia-reperfusion group, compared with sham group. In conclusion, miR-21 expression is upregulated during intestinal barrier dysfunction induced by IRI. miR-21 may play an important role in the regulation of intestinal barrier function.


Assuntos
Mucosa Intestinal/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Marcação In Situ das Extremidades Cortadas , Intestinos , Masculino , MicroRNAs/genética , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Traumatismo por Reperfusão/genética
20.
Chem Commun (Camb) ; 54(88): 12447-12450, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30280730

RESUMO

Silicon nanocomposites with surface coating have been promising candidates for high-performance anodes in Li-ion batteries. Here we report a simple yet effective way to synthesize Si@SiO2 nanocomposites with amorphous SiO2 coating through a fluoride ion-mediated continuous etching-redeposition process. The Si@SiO2 nanocomposite anode exhibits significantly improved lithium storage properties, with a reversible capacity of 1356 mA h g-1 at 2.1 A g-1 for 300 cycles.

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