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1.
J Colloid Interface Sci ; 557: 664-672, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31561083

RESUMO

The development of high-performance non-precious metal electrocatalysts is of great importance for construction of next generation fuel cells. Herein, we report for the first time the creation of new metal-free porous carbon framework catalysts derived from N-rich hypercrosslinked polymers (HCPs) using pyrrole as building blocks for oxygen reduction reaction (ORR) (denoted as PCF-HCPs). The PCF-HCPs obtained at the pyrolysis temperature of 900 °C (PCF-HCP-900), displayed outstanding catalytic activity towards the ORR compared with other PCF-HCPs pyrolysis temperature. Due to PCF-HCP-900 with large specific surface, excellent porosity and, importantly, exposed active sites caused by N doping with high density, the catalysts exhibited outstanding ORR activity in alkaline medium, i.e., the PCF-HCP-900 yielded a half-wave potential of 0.84 V, which was 10 mV higher than that of the state of-the-art Pt/C catalyst (0.83 V), and onset potential of 0.95 V (vs. RHE), a high diffusion limiting current density of 4.8 mA cm-2, better methanol tolerance and long-term stability (2 mV negative shift after 3000 potential cycles) than commercial Pt/C. Furthermore, PCF-HCP-900 shows a favorable 4-electron transfer process (n ≈ 3.96) and lower H2O2 yield. Based on these merits, the PCF-HCP-900 may open a new possibility for design of ORR metal-free catalyst of fuel-cell technologies.

2.
J Orthop Surg Res ; 14(1): 258, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412883

RESUMO

BACKGROUND: Failed back surgery syndrome (FBSS) is a common complication after the laminectomy. Epidural fibrosis is the major cause of lower back pain and other complications. Numerous studies have shown that apigenin (API) could treat various fibrotic diseases by regulating various signaling pathways, whereas no study has discussed whether API can inhibit fibroblast proliferation and reduce epidural fibrosis after the laminectomy by regulating Wnt3a/ß-catenin signaling pathway. METHODS: Human fibroblasts were cultured and treated with API in different concentrations for 24 h. CCK-8 detection and EdU incorporation assay were performed to detect cell viability and cell proliferation. Western blotting analysis was applied to detect expressions of proliferative proteins, Wnt3a, and its downstream proteins. Moreover, the Wnt3a gene was overexpressed in fibroblasts to define the relationship between Wnt3a/ß-catenin signaling pathway and fibroblast proliferation. Wnt3a overexpressed fibroblasts were treated with API to verify if it could reverse the effects of API treatment. Twenty-four Sprague-Dawley rats were randomly divided into four groups. Laminectomy was performed and the rats were gavaged with different doses of API or 5% sodium carboxyl methyl cellulose (CMC-Na) solution for 1 month. The abilities of API to inhibit fibroblast proliferation and to reduce epidural fibrosis were evaluated using histological and immunohistochemical analysis. RESULTS: CCK-8 detection and EdU incorporation assay demonstrated that API could inhibit the viability and proliferation rate of fibroblasts in a concentration-dependent manner. The Western blotting analysis revealed that API could inhibit the expressions of PCNA, cyclinD1, Wnt3a, and its downstream proteins. The overexpression of Wnt3a in fibroblasts could upregulate the expressions of proliferative proteins such as PCNA and cyclinD1. The inhibitory effect of API on PCNA, Wnt3a, and its downstream proteins was partially reversed by overexpression of Wnt3a. Moreover, the results of the histological and immunohistochemical analysis revealed that API could reduce the epidural fibrosis in rats by inhibiting fibroblast proliferation in a dose-dependent manner. CONCLUSIONS: API can inhibit fibroblast proliferation and reduce epidural fibrosis by suppressing Wnt3a/ß-catenin signaling pathway, which can be adopted as a new option to prevent epidural fibrosis after the laminectomy.

3.
Org Lett ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31407584

RESUMO

A cyclodipeptide synthase-containing gene cluster (pcm) was identified in Streptomyces chrestomyceticus NA4264 through genome mining. Heterologous expression of the cryptic pcm gene cluster in Streptomyces albus led to the production of a new highly modified cyclodipeptide named purincyclamide (1). Bioinformatic analysis and gene knockout experiments revealed the biosynthetic pathway. The production of 1 was achieved through a one-pot enzymatic reaction.

4.
Phytomedicine ; 63: 152986, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31310912

RESUMO

BACKGROUND: Polygonum cuspidatum has been used in traditional Chinese medicine to treat liver disorders associated with oxidative stress, inflammation and lipid accumulation for centuries in patients. PURPOSE: The aim of this study was to examine whether P. cuspidatum extract (PCE) prevented against fructose-induced liver lipid accumulation via regulating Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. METHOD: PCE was administered orally to male Sprague-Dawley rats given 10% fructose drinking water for 6 weeks at 80 and 160 mg/kg once daily for 11 weeks. RESULTS: PCE significantly alleviated liver lipid accumulation in fructose-fed rats with metabolic syndrome. It also inhibited Keap1, activated Nrf2 antioxidant pathway, resulting in the suppression of oxidative stress, evidenced by reducing hydrogen peroxide (H2O2), malondialdehyde (MDA) and hydroxy radical (OH•) levels, and increasing glutathione (GSH)/oxidized glutathione (GSSG) ratio as well as superoxidase dismutase (SOD) and catalase (CAT) activity in the liver of fructose-fed rats. Additionally, PCE up-regulated peroxisome proliferator activated receptor-α (PPAR-α), and down-regulated sterol regulatory element binging protein 1 (SREBP-1), fatty acid synthetase (FAS) and stearoyl-CoA desaturase-1 (SCD-1) in this animal model, being consistent with its reduction of triglyceride (TG) levels. CONCLUSION: These results demonstrate that PCE reduces oxidative stress, and prevent lipid accumulation in the liver of fructose-fed rats possibly by targeting the Keap1/Nrf2 pathway. PCE may be a promising therapeutic strategy for fructose-associated liver lipid accumulation.

5.
Chin J Nat Med ; 17(6): 475-480, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262460

RESUMO

Three new phenazine-type compounds, named phenazines SA-SC (1-3), together with four new natural products (4-7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1-5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.

6.
Chin J Nat Med ; 17(5): 387-393, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31171274

RESUMO

Replacement of the native promoter of theglobal regulator LaeA-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher's reaction, and electronic circular dichroism (ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.

7.
Rev Sci Instrum ; 90(5): 054708, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31153239

RESUMO

A ultralow noise magnetic field is essential for many branches of scientific research. Examples include experiments conducted on ultracold atoms, quantum simulations, and precision measurements. In ultracold atom experiments specifically, a bias magnetic field will often serve as a quantization axis and be applied for Zeeman splitting. As atomic states are usually sensitive to magnetic fields, a magnetic field characterized by ultralow noise as well as high stability is typically required for experimentation. For this study, a bias magnetic field is successfully stabilized at 14.5 G, with the root mean square value of the noise reduced to 18.5 µG (1.28 ppm) by placing µ-metal magnetic shields together with a dynamical feedback circuit. Long-time instability is also regulated consistently below 7 µG. The level of noise exhibited in the bias magnetic field is further confirmed by evaluating the coherence time of a Bose-Einstein condensate characterized by Rabi oscillation. It is concluded that this approach can be applied to other physical systems as well.

8.
Exp Appl Acarol ; 78(3): 327-342, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31250238

RESUMO

Pyemotes zhonghuajia Yu, Zhang and He is a newly discovered native ectoparasitic mite that efficiently controls stem borers in China. To provide a steady and sufficient supply, extend adult lifespan and synchronize field augmentative releases of P. zhonghuajia, we determined the optimal cold storage temperature and duration by storing 1-day-old mated females at 8, 10 and 12 °C for 10-90 days with a 10-day interval in the laboratory. We then recorded mite survival during storage and monitored the post-storage reproductive performance of mites at a control temperature of 25 °C. We found that all mites survived at 10 and 12 °C for different durations, but mortality occurred when mites were stored at 8 °C for ≥ 30 days with more than 70% of mites dead when the storage duration prolonged up to 50 days. The proportion of reproductive females was higher at 10 °C but decreased with the prolonged storage duration at all test temperatures. Storage temperature had no significant effect on the pre-reproductive period and offspring sex ratio, whereas prolonged storage induced longer pre-reproductive period and lower proportion of female offspring. The reproductive period increased with increasing storage temperature and with prolonged storage up to 50 and 60 days; however, the longer reproductive period did not directly translate into greater reproductive output. We found that compared with the control, mites stored at 10 °C for up to 30 days did not significantly reduce their survival, proportion of reproductive success and number and sex ratio of offspring, suggesting that 10 °C and ≤ 30 days were the optimal cold storage temperature and duration, respectively, for post-mass production storage before the field augmentative release of P. zhonghuajia.

9.
Clin Rehabil ; 33(9): 1479-1491, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31081365

RESUMO

OBJECTIVE: The aim of this study was to validate a novel pictorial-based Longshi Scale for evaluating a patient's disability by healthcare professionals and non-professionals. DESIGN: Prospective study. SETTING: Rehabilitation departments from a grade A, class 3 public hospital, a grade B, class 2 public hospital, and a private hospital and seven community rehabilitation centers. SUBJECTS: A total of 618 patients and 251 patients with functional disabilities were recruited in a two-phase study, respectively. MAIN MEASURES: Outcome measure: pictorial scale of activities of daily living (ADLs, Longshi Scale). Reference measure: Barthel Index. The Spearman correlation coefficient was used to analyze the validity of Longshi Scale against Barthel Index. RESULTS: In phase 1 study, from March 2016 to August 2016, the results demonstrated that the Longshi Scale was both reliable and valid (intraclass correlation coefficient based on two-way random effect (ICC2,1) = 0.877-0.974 for intra-rater reliability; ICC2,1 = 0.928-0.979; κ = 0.679-1.000 for inter-rater reliability; intraclass correlation coefficient based on one-way random effect (ICC1,1) = 0.921-0.984 for test-retest reliability and Spearman correlation coefficient = 0.836-0.899). In the second phase, in March 2018, results further demonstrated that the Longshi Scale had good inter-rater and intra-rater reliability among healthcare professionals and non-professionals including therapists, interns, and personal care aids (ICC1,1 = 0.822-0.882 on Day 1; ICC1,1 = 0.842-0.899 on Day 7 for inter-rater reliability). In addition, the Longshi Scale decreased assessment time significantly, compared with the Barthel Index assessment (P < 0.01). CONCLUSION: The Longshi Scale could potentially provide an efficient way for healthcare professionals and non-professionals who may have minimal training to assess the ADLs of functionally disabled patients.

10.
J Nat Prod ; 82(6): 1503-1509, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31117520

RESUMO

Six new macrolides named myrothecines D-G (1-4), 16-hydroxymytoxin B (5), and 14'-dehydrovertisporin (6), including four 10,13-cyclotrichothecane derivatives, in addition to 12 known compounds (7-18), were isolated from three endophytic Myrothecium roridum, IFB-E008, IFB-E009, and IFB-E012. The isolated compounds were characterized by MS, NMR, CD, and single-crystal X-ray crystallography. The isolated macrolides exhibited an antiproliferation effect against chronic myeloid leukemia K562 and colorectal carcinoma SW1116 cell lines. Compounds 1-6 were cytotoxic, with IC50 values ranging between 56 nM and 16 µM. Since slight structural changes led to obvious activity differences, the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods were then used to explore the 3D QSAR (three-dimensional quantitative structure-activity relationship) of these macrolides. The result showed that the steric, electrostatic, hydrophobic, and H-bond acceptor factors were involved in their cytotoxicity and provided an in-depth understanding of the structure-activity relationships of these metabolites.

11.
Food Chem Toxicol ; 129: 13-21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31014900

RESUMO

Cadmium (Cd) has been generally recognized as an endocrine-disrupting chemical for its toxic effects on the hypothalamus-pituitary-gonadal (HPG) axis accompanied by dysfunction in sex hormone secretion. Particularly, exposure to Cd during puberty versus post-puberty exhibits differing age-dependent effects that require further examination. This study sought to determine if cyanidin-3-O-glucoside (C3G), a typical anthocyanin with neuroprotective bioactivity, could protect against Cd-induced sex hormone-disorder in Pubertal male mice. C3G treatment reversed the disruption of hormone levels and increased Gnrh1 gene expression in the hypothalamus. In addition, the levels of gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH), were reversed by C3G. Interestingly, C3G improved the expression of LH and FSH receptor in the testis in mice exposed to Cd. Furthermore, C3G activated the signaling pathway related to the synthesis of testosterone processing. In conclusion, C3G protected against Cd-induced dysfunction of sex hormone secretion through the regulation of the HPG axis in male mice during puberty. The results of this study suggest that consumption of anthocyanins can be protective against metal-induced male reproductive dysfunction.


Assuntos
Antocianinas/farmacologia , Cádmio/toxicidade , Glucosídeos/farmacologia , Hormônios Esteroides Gonadais/metabolismo , Gônadas/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Maturidade Sexual , Animais , Peso Corporal/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Gônadas/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Camundongos
12.
Org Lett ; 21(10): 3785-3788, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31033301

RESUMO

Genome mining of the marine Streptomyces seoulensis A01 enabled the identification of a giant type I polyketide synthase gene cluster ( asm). Heterologous expression of the cryptic asm cluster using a bacterial artificial chromosome vector in heterologous host led to the production of ansaseomycins A (1) and B (2). A plausible biosynthetic pathway was also proposed. Additionally, compounds 1 and 2 are active against K562 cell lines with IC50 values of 13.3 and 18.1 µM, respectively.


Assuntos
Lactamas Macrocíclicas/metabolismo , Policetídeo Sintases/metabolismo , Streptomyces/metabolismo , Vias Biossintéticas , Cromossomos Artificiais Bacterianos , Lactamas Macrocíclicas/química , Estrutura Molecular , Família Multigênica , Policetídeo Sintases/química , Policetídeo Sintases/genética , Streptomyces/química , Streptomyces/genética
13.
Eur J Pharmacol ; 854: 149-158, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-30995437

RESUMO

Intraarticular fibrosis following knee surgery is a troublesome complication and remains a challenging problem for clinicians. Artesunate (ART), a classical anti-malarial drug extracted from the Chinese medicinal herb Artemisia annua L, has been associated with some fibrosis-related diseases. However, its effect and underlying mechanism on knee arthrofibrosis are still obscure. In the present study, we found that ART induced cellular autophagy flux and inhibited cell proliferation in fibroblasts. Intriguingly, genetic depletion of Beclin-1 abolished ART-triggered cellular autophagy and further attenuated the inhibitory effect of ART on fibroblasts proliferation. Moreover, at molecular level, our results demonstrated that ART-induced autophagy activation was associated with the inhibition of mTOR signaling through PI3K/AKT/mTOR pathway and AMPK/mTOR pathway. In vivo, ART treatment triggered autophagy activation and alleviated the severity of surgery-induced knee arthrofibrosis. Taken together, we concluded that ART exhibited anti-proliferation efficacy in fibroblasts and alleviated the severity of knee arthrofibrosis in rabbits by inducing Beclin-1-mediated autophagy via inhibition of mTOR signaling. These findings indicated that ART might be a potential therapeutic agent for preventing the progression of surgery-induced intraarticular fibrosis of knee.

14.
Food Chem Toxicol ; 128: 97-105, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30914357

RESUMO

Cadmium (Cd) is a poisonous metal that is toxic for male reproduction. Cyanidin-3-O-glucoside (C3G) as typical anthocyanin benefits many organs. In this study, we investigated the protective effects and associated underlying mechanisms of C3G against the toxicity of Cd on male reproduction in rat Leydig cell line R2C cells. Cells were pre-protected with C3G (5-160 µmol/L) for 2 h and then treated with cadmium sulfate (CdSO4) (10-160 µmol/L) for 24 h. The results showed that cytotoxicity, mitochondrial damage, superoxide dismutase 2 (SOD2), and overproduction of reactive oxygen species (ROS) in CdSO4-treated R2C cells were significantly reduced with C3G pre-treatment. Moreover, C3G pre-treatment led to upregulated expression of steroidogenic acute regulatory (StAR) protein and progesterone production. Our study suggests that C3G may be a potential therapeutic agent against Cd-induced reproductive toxicity.


Assuntos
Antocianinas/farmacologia , Compostos de Cádmio/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Glucosídeos/farmacologia , Mitocôndrias/efeitos dos fármacos , Progesterona/metabolismo , Sulfatos/toxicidade , Animais , Linhagem Celular , Células Intersticiais do Testículo/enzimologia , Células Intersticiais do Testículo/metabolismo , Masculino , Metaloproteinases da Matriz/metabolismo , Fosfoproteínas/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Regulação para Cima/efeitos dos fármacos
15.
Nature ; 568(7750): 122-126, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30867595

RESUMO

Pericyclic reactions are powerful transformations for the construction of carbon-carbon and carbon-heteroatom bonds in organic synthesis. Their role in biosynthesis is increasingly apparent, and mechanisms by which pericyclases can catalyse reactions are of major interest1. [4+2] cycloadditions (Diels-Alder reactions) have been widely used in organic synthesis2 for the formation of six-membered rings and are now well-established in biosynthesis3-6. [6+4] and other 'higher-order' cycloadditions were predicted7 in 1965, and are now increasingly common in the laboratory despite challenges arising from the generation of a highly strained ten-membered ring system8,9. However, although enzyme-catalysed [6+4] cycloadditions have been proposed10-12, they have not been proven to occur. Here we demonstrate a group of enzymes that catalyse a pericyclic [6+4] cycloaddition, which is a crucial step in the biosynthesis of streptoseomycin-type natural products. This type of pericyclase catalyses [6+4] and [4+2] cycloadditions through a single ambimodal transition state, which is consistent with previous proposals11,12. The [6+4] product is transformed to a less stable [4+2] adduct via a facile Cope rearrangement, and the [4+2] adduct is converted into the natural product enzymatically. Crystal structures of three pericyclases, computational simulations of potential energies and molecular dynamics, and site-directed mutagenesis establish the mechanism of this transformation. This work shows how enzymes are able to catalyse concerted pericyclic reactions involving ambimodal transition states.


Assuntos
Biocatálise , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Reação de Cicloadição , Enzimas/metabolismo , Lactonas/química , Lactonas/metabolismo , Cristalografia por Raios X , Teoria da Densidade Funcional , Enzimas/química , Enzimas/genética , Simulação de Dinâmica Molecular , Conformação Proteica , Termodinâmica
16.
J Nat Prod ; 82(4): 792-797, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-30794407

RESUMO

Six novel aromatic polyketide dimers, bialternacins A-F (1-6), were isolated from a plant endophytic Alternaria sp. The structures of compounds 1-6 were elucidated on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism analysis. Compounds 1, 2, 5, and 6 were characterized as four pairs of racemic mixtures. Compound (+)-5 was demonstrated to show acetylcholinesterase inhibitory activity with an IC50 value of 15.5 µM. A putative biosynthetic pathway for these compounds was proposed.

17.
Br J Pharmacol ; 176(11): 1619-1634, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30632134

RESUMO

BACKGROUND AND PURPOSE: Excessive fructose consumption is a risk factor for liver fibrosis. Pterostilbene protects against liver fibrosis. Here, we investigated the potential role and the mechanisms underlying the hepatocyte epithelial-mesenchymal transition (EMT) in fructose-induced liver fibrosis and protection by pterostilbene. EXPERIMENTAL APPROACH: Characteristic features of liver fibrosis in 10% fructose-fed rats and EMT in 5 mM fructose-exposed BRL-3A cells with or without pterostilbene and the change of miR-34a/Sirt1/p53 and transforming growth factor-ß1 (TGF-ß1)/Smads signalling were examined. MiR-34a inhibitor, miR-34a minic, or p53 siRNA were used to explore the role of miR-34a/Sirt1/p53 signalling in fructose-induced EMT and the action of pterostilbene. KEY RESULTS: Pterostilbene prevented fructose-induced liver injury with fibrosis in rats. Fructose caused hepatocyte undergoing EMT, gaining fibroblast-specific protein 1 and vimentin, and losing E-cadherin, effects attenuated by pterostilbene. Moreover, fructose induced miR-34a overexpression in hepatocytes with down-regulated Sirt1, increased p53 and ac-p53, and activated TGF-ß1/Smads signalling, whereas these disturbances were suppressed by miR-34a inhibitor. Additionally, miR-34a inhibitor and p53 siRNA prevented TGF-ß1-driven hepatocyte EMT under fructose exposure. Pterostilbene down-regulated miR-34a, up-regulated Sirt1, and suppressed p53 activation and TGF-ß1/Smads signalling in fructose-stimulated animals and cells but showed no additional effects with miR-34a inhibitor on miR-34a/Sirt1/p53 signalling in fructose-exposed hepatocytes. CONCLUSIONS AND IMPLICATIONS: These results strongly suggest that activation of miR-34a/Sirt1/p53 signalling is required for fructose-induced hepatocyte EMT mediated by TGF-ß1/Smads signalling, contributing to liver fibrosis in rats. Pterostilbene exhibits a protective effect against liver fibrosis at least partly through inhibiting miR-34a/Sirt1/p53 signalling activation.

19.
Acta Pharmacol Sin ; 40(7): 879-894, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30568253

RESUMO

Increasing evidence has demonstrated that excessive fructose intake induces liver fibrosis. Epithelial-mesenchymal transition (EMT) driven by transforming growth factor-ß1 (TGF-ß1)/mothers against decapentaplegic homolog (Smad) signaling activation promotes the occurrence and development of liver fibrosis. Magnesium isoglycyrrhizinate is clinically used as a hepatoprotective agent to treat liver fibrosis, but its underlying molecular mechanism has not been identified. Using a rat model, we found that high fructose intake reduced microRNA (miR)-375-3p expression and activated the janus-activating kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) cascade and TGF-ß1/Smad signaling, which is consistent with the EMT and liver fibrosis. To further verify these observations, BRL-3A cells and/or primary rat hepatocytes were exposed to high fructose and/or transfected with a miR-375-3p mimic or inhibitor or treated with a JAK2 inhibitor, and we found that the low expression of miR-375-3p could induce the JAK2/STAT3 pathway to activate TGF-ß1/Smad signaling and promote the EMT. Magnesium isoglycyrrhizinate was found to ameliorate high fructose-induced EMT and liver fibrosis in rats. More importantly, magnesium isoglycyrrhizinate increased miR-375-3p expression to suppress the JAK2/STAT3 pathway and TGF-ß1/Smad signaling in these animal and cell models. This study provides evidence showing that magnesium isoglycyrrhizinate attenuates liver fibrosis associated with a high fructose diet.

20.
Nat Prod Res ; : 1-7, 2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-30450968

RESUMO

A novel lactone-type norcucurbitacin, designated as neocucurbitacin D (1), together with five known cucurbitane triterpenes were isolated from traditional Tibetan medicine "Se Ji Mei Duo", which is the seed of Herpetospermum pedunculosum (Ser.) C.B. Clarke. The structure of neocucurbitacin D was elucidated by spectroscopic analysis, including 2D NMR and X-ray techniques. Compounds 1-6 were screened for their xanthine oxidase (XOD) inhibitory activity. Compound 1, 2 and 4 exhibited significant XOD inhibition with IC50 values ranging from 10.16 to 18.41 µM. The absolute stereochemistry and XOD inhibitiory activity of lactone-type norcucurbitacins was reported firstly.

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