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1.
Cell Death Dis ; 11(2): 91, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019910

RESUMO

Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Genomic studies have revealed that HCC is a heterogeneous disease with multiple subtypes. BRG1, encoded by the SMARCA4 gene, is a key component of SWI/SNF chromatin-remodeling complexes. Based on TCGA studies, somatic mutations of SMARCA4 occur in ~3% of human HCC samples. Additional studies suggest that BRG1 is overexpressed in human HCC specimens and may promote HCC growth and invasion. However, the precise functional roles of BRG1 in HCC remain poorly delineated. Here, we analyzed BRG1 in human HCC samples as well as in mouse models. We found that BRG1 is overexpressed in most of human HCC samples, especially in those associated with poorer prognosis. BRG1 expression levels positively correlate with cell cycle and negatively with metabolic pathways in the Cancer Genome Atlas (TCGA) human HCC data set. In a murine HCC model induced by c-MYC overexpression, ablation of the Brg1 gene completely repressed HCC formation. In striking contrast, however, we discovered that concomitant deletion of Brg1 and overexpression of c-Met or mutant NRas (NRASV12) triggered HCC formation in mice. Altogether, the present data indicate that BRG1 possesses both oncogenic and tumor-suppressing roles depending on the oncogenic stimuli during hepatocarcinogenesis.

2.
J Cell Mol Med ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32003123

RESUMO

Preeclampsia is a severe pregnancy-related disease that is found in 3%-5% of pregnancies worldwide and is primarily related to the decreased proliferation and invasion of trophoblast cells and abnormal uterine spiral artery remodelling. However, studies on the pathogenesis of placental trophoblasts are insufficient, and the aetiology of PE remains unclear. Here, we report that endothelial protein C receptor (EPCR), a transmembrane glycoprotein, was down-regulated in placentas from preeclamptic patients. Moreover, lack of EPCR significantly reduced the trophoblast cell proliferation, invasion and tube formation capabilities. Microscale thermophoresis analysis showed that EPCR directly bound to protease-activated receptor 1 (PAR-1), a G protein-coupled receptor. This change resulted in a substantial reduction in active Rac1 and caused excessive actin rearrangement. Our findings reveal a previously unidentified role of EPCR in the regulation of trophoblast proliferation, invasion and tube formation through promotion of actin polymerization, which is required for normal placental development.

3.
Nutrients ; 12(2)2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32074961

RESUMO

The root of Platycodon grandiflorus (PG), with hepatoprotective and anti-oxidation effects, has a long history of being used as food and herbal medicine in Asia. However, the mechanism of PG against non-alcoholic fatty liver disease (NAFLD) is still not clear. The aim of this study was to investigate the mechanism of PG suppressing the development of NAFLD induced by a high-fat diet (HFD) in mice. Male C57BL/6J mice were fed with either a standard chow diet or a HFD, either supplemented with or without PG, for 16 weeks. Serum lipids, liver steatosis, oxidative stress and insulin sensitivity were determined. Expressions or activities of hepatic enzymes in the related pathways were analyzed to investigate the mechanisms. PG significantly reduced HFD-induced hepatic injury and hyperlipidemia, as well as hepatic steatosis via regulating phosphorylation of acetyl-CoA carboxylase (p-ACC) and expression of fatty acid synthase (FAS). In addition, PG ameliorated oxidative stress by restoring glutathione (GSH) content and antioxidant activities, and improved insulin sensitivity by regulating the PI3K/Akt/GSK3ß signaling pathway. Our data showed that dietary PG have profound effects on hepatic insulin sensitivity and oxidative stress, two key factors in the pathogenesis of NAFLD, demonstrating the potential of PG as a therapeutic strategy for NAFLD.

4.
Microb Cell Fact ; 19(1): 32, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054531

RESUMO

BACKGROUND: Bleomycin is a broad-spectrum glycopeptide antitumor antibiotic produced by Streptomyces verticillus. Clinically, the mixture of bleomycin A2 and bleomycin B2 is widely used in combination with other drugs for the treatment of various cancers. As a secondary metabolite, the biosynthesis of bleomycin is precisely controlled by the complex extra-/intracellular regulation mechanisms, it is imperative to investigate the global metabolic and regulatory system involved in bleomycin biosynthesis for increasing bleomycin production. RESULTS: N-acetylglucosamine (GlcNAc), the vital signaling molecule controlling the onset of development and antibiotic synthesis in Streptomyces, was found to increase the yields of bleomycins significantly in chemically defined medium. To mine the gene information relevant to GlcNAc metabolism, the DNA sequences of dasR-dasA-dasBCD-nagB and nagKA in S. verticillus were determined by chromosome walking. From the results of Real time fluorescence quantitative PCR (RT-qPCR) and electrophoretic mobility shift assays (EMSAs), the repression of the expression of nagB and nagKA by the global regulator DasR was released under induction with GlcNAc. The relief of blmT expression repression by BlmR was the main reason for increased bleomycin production. DasR, however, could not directly affect the expression of the pathway-specific repressor BlmR in the bleomycins gene cluster. With at the beginning of bleomycin synthesis, the supply of the specific precursor GDP-mannose played the key role in bleomycin production. Genetic engineering of the GDP-mannose synthesis pathway indicated that phosphomannose isomerase (ManA) and phosphomannomutase (ManB) were key enzymes for bleomycins synthesis. Here, the blmT, manA and manB co-expression strain OBlmT/ManAB was constructed. Based on GlcNAc regulation and assisted metabolic profiling analysis, the yields of bleomycin A2 and B2 were ultimately increased to 61.79 and 36.9 mg/L, respectively. CONCLUSIONS: Under GlcNAc induction, the elevated production of bleomycins was mainly associated with the alleviation of the inhibition of BlmT, so blmT and specific precursor synthesis pathways were genetically engineered for bleomycins production improvement. Combination with subsequent metabolomics analysis not only effectively increased the bleomycin yield, but also extended the utilization of chitin-derived substrates in microbial-based antibiotic production.

5.
Cereb Cortex ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080708

RESUMO

The corpus callosum is the commissural bridge of white-matter bundles important for the human brain functions. Previous studies have analyzed the structural links between cortical gray-matter networks and subregions of corpus callosum. While meaningful white-matter functional networks (WM-FNs) were recently reported, how these networks functionally link with distinct subregions of corpus callosum remained unknown. The current study used resting-state functional magnetic resonance imaging of the Human Connectome Project test-retest data to identify 10 cerebral WM-FNs in 119 healthy subjects and then parcellated the corpus callosum into distinct subregions based on the functional connectivity between each callosal voxel and above networks. Our results demonstrated the reproducible identification of WM-FNs and their links with known gray-matter functional networks across two runs. Furthermore, we identified reliably parcellated subregions of the corpus callosum, which might be involved in primary and higher order functional systems by functionally connecting with WM-FNs. The current study extended our knowledge about the white-matter functional signals to the intrinsic functional organization of human corpus callosum, which could help researchers understand the neural substrates underlying normal interhemispheric functional connectivity as well as dysfunctions in various mental disorders.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32027477

RESUMO

Burn infection is one of the commonest causes of death in severely burned patients. Developing multifunctional biological nanomaterials has a great significance for the comprehensive treatment of burn infection. In this paper, we developed a hydrogel-based nanodelivery system with antibacterial activity and skin regeneration function, which was used for photodynamic antimicrobial chemotherapy (PACT) in the treatment of burns. The treatment system is mainly composed of porphyrin photosensitizer sinoporphyrin sodium (DVDMS) and poly(lactic-co-glycolic acid) (PLGA)-encapsulated basic fibroblast growth factor (bFGF) nanospheres that are embedded in carboxymethyl chitosan (CMCS)-sodium alginate to form CSDP hybrid hydrogel. We systematically evaluated the inherent antibacterial performance, rheological properties, fluorescence imaging, and biocompatibility of the CSDP nanosystem. Under mild photoirradiation (30 J/cm2, 5 min), 10 µg/mL CSDP showed excellent antibacterial and anti-biofilm activities, which eradicated almost 99.99% of Staphylococcus aureus and multidrug-resistant (MDR) S. aureus in vitro. KEGG analysis identified that multiple signaling pathways were changed in MDR S. aureus after PACT. In the burn-infection model, CSDP-PACT successfully inhibited bacteria growth and concurrently promoted wound healing. Moreover, several regenerative factors were increased and some proinflammatory factors were reduced in the burn wounds of CSDP hydrogel treatment. These results suggest that the multifunctional CSDP hydrogel is a portable, light-triggered, antibacterial theranostic-platform and CSDP-PACT provides a promising strategy or the mechanically based synergistic treatment of burn infections.

7.
Am J Pathol ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32035060

RESUMO

Liver regeneration is a fundamental biological process required for sustaining body homeostasis and restoring liver function after injury. Emerging evidence demonstrates that cytokines, growth factors and multiple signaling pathways contribute to liver regeneration. Mammalian target of rapamycin complex 2 (mTORC2) was identified to regulate cell metabolism, proliferation and survival. The major substrates for mTORC2 are the AGC-family members of kinases, including AKT, SGK and PKC-α. Here, we investigated the functional roles of mTORC2 during liver regeneration. For this purpose, we performed partial hepatectomy (PHx) in liver specific Rictor (the pivotal unit of mTORC2 complex) knockout (RictorLKO) and wild-type (Rictorfl/fl) mice. We discovered that Rictor deficient mice are more intolerant to PHx and display higher mortality after PHx. Mechanistically, loss of Rictor resulted in decreased Akt phosphorylation, leading to a delay in hepatocyte proliferation and lipid droplets formation along liver regeneration. Overall, these results indicate an essential role of the mTORC2 signaling pathway during liver regeneration.

8.
Nano Lett ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32013449

RESUMO

Highly efficient information processing in the brain is based on processing and memory components called synapses, whose output is dependent on the history of the signals passed through them. Here, we have developed an artificial synapse with both electrical and optical memory effects using chemical transformations in plasmonic tunnel junctions. In an electronic implementation, the electrons tunneled into plasmonic nanorods under a low bias voltage are harvested to write information into the tunnel junctions via hot-electron-mediated chemical reactions with the environment. In an optical realization, the information can be written by an external light illumination to excite hot electrons in the plasmonic nanorods. The stored information is nonvolatile and can be read either electrically or optically by measuring the resistance or inelastic-tunneling-induced light emission, respectively. The described architecture provides a high density (∼1010 cm-2) of memristive optoelectronic devices which can be used as multilevel nonvolatile memory, logic units, or artificial synapses in future electronic, optoelectronic, and artificial neural networks.

9.
BMC Genomics ; 21(1): 52, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31948405

RESUMO

BACKGROUND: Pennisetum giganteum, an abundant, fast-growing perennial C4 grass that belongs to the genus Pennisetum, family Poaceae, has been developed as a source of biomass for mushroom cultivation and production, as a source of forage for cattle and sheep, and as a tool to remedy soil erosion. However, having a chilling-sensitive nature, P. giganteum seedlings need to be protected while overwintering in most temperate climate regions. RESULTS: To elucidate the cold stress responses of P. giganteum, we carried out comprehensive full-length transcriptomes from leaf and root tissues under room temperature (RT) and chilling temperature (CT) using PacBio Iso-Seq long reads. We identified 196,124 and 140,766 full-length consensus transcripts in the RT and CT samples, respectively. We then systematically performed functional annotation, transcription factor identification, long non-coding RNAs (lncRNAs) prediction, and simple sequence repeat (SSR) analysis of those full-length transcriptomes. Isoform analysis revealed that alternative splicing events may be induced by cold stress in P. giganteum, and transcript variants may be involved in C18 unsaturated fatty acid biosynthesis and metabolism pathways at chilling temperature in P. giganteum. Furthermore, the fatty acid composition determination and gene expression level analysis supported that C18 unsaturated fatty acid biosynthesis and metabolism pathways may play roles during cold stress in P. giganteum. CONCLUSIONS: We provide the first comprehensive full-length transcriptomic resource for the abundant and fast-growing perennial grass Pennisetum giganteum. Our results provide a useful transcriptomic resource for exploring the biological pathways involved in the cold stress responses of P. giganteum.

10.
Phys Chem Chem Phys ; 22(4): 2557-2565, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31942907

RESUMO

Molecular dynamics simulations of Ni36Zr64, Cu65Zr35 and Ni80Al20 were carried out over a broad range of temperature (900-3000 K) to investigate the Stokes-Einstein (SE) relation for glass-forming melts. Our results reproduce experimental structural and transport properties. Results show that the breakdown temperature of the SE relation (TSE) equals the dynamical crossover temperature (TA) and both are roughly twice the glass-transition temperature (Tg) for the three glass-forming melts (TSE = TA ≈ 2.0Tg). The product of the individual component self-diffusion coefficient and viscosity Dαη can be roughly regarded as a constant at the transition zone (a small temperature range around TSE) in which the temperature behaviors of self-diffusion coefficient and viscosity switch from high-temperature Arrhenius to a low-temperature VFT behavior. Below TSE, the decoupling of component diffusion coefficients was found. In particular, the decoupling of component diffusion coefficients can be ascribed to the decoupling of the partial pair structural correlation of components, which can be clearly reflected by the intersection of the high-temperature and low-temperature behaviors of the ratio between the partial pair correlation entropy of components (Sß2/Sα2). Furthermore, the ratio between the partial pair correlation entropy of components may be used to predict the validity of the SE relation, in the absence of both transport coefficients and atomic coordinates.

11.
Rev Soc Bras Med Trop ; 53: e20190211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31994661

RESUMO

INTRODUCTION: Anopheles stephensi is the main malaria vector in Southeast Asia. Recently, plant-sourced larvicides are attracting great interests. METHODS: The essential oil was extracted from the leaf of Cinnamomum camphora (L.), and a bioassay was conducted to determine the larvicidal efficacy. The chemical composition of the essential oil was determined by GC-MS analysis. RESULTS: The oil showed strong, dose-dependent larvicidal activities. The onset of larvicidal efficiency was rapid. The LC50 and LC95 were determined as 0.146% and 1.057% at 1 h, 0.031% and 0.237% at 12 h, 0.026% and 0.128% at 24 h, respectively. The oil contains 32 compounds. CONCLUSIONS: The essential oil of C. camphora leaf has an excellent larvicidal potential for the control of A. stephensi.

12.
J Appl Clin Med Phys ; 21(2): 67-72, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31925999

RESUMO

PURPOSE: To demonstrate a specific skin dose limiting technique in radiotherapy treatment planning for esophageal cancer and carry out a comparative analysis combining with clinical cases. MATERIAL AND METHODS: Thirty patients with cervical and upper thoracic esophageal carcinoma previously treated in our institution were selected. A treatment plan had been finished previously according to the planning parameters directives from physician and delivered for each patient. In this study, we copied the previously delivered plans in radiotherapy treatment planning system and converted a low dose level (usually 5Gy) to a skin dose limiting structure (SDLS), then we set the objective functions of the SDLS in the Pinnacle Inverse Planning module and re-optimize the plans to reduce the skin doses. Finally, we compared the dose distribution and other parameters of target volume and organs at risk (OARs) between the old plans and the new plans. RESULTS: There was no significant difference in most of OARs sparing. However, for all plans, the maximum dose to the SDLS decreased from 6145.90 ± 416.96 cGy to 5562.09 ± 616.69 cGy with maximum difference of 1361.30 cGy (P < 0.05), the percentage volume of 40Gy received by the SDLS decreased from (10.20 ± 6.36)% to (5.46 ± 4084)% with maximum difference of 9.89% (P < 0.05). For the target volume, there was no significant difference in the average dose and maximum dose, the approximate minimum dose to the target volume decreased from 5711.28 ± 164.61 cGy to 5584.93 ± 157.70 cGy (P < 0.05), the conformal index and homogeneity index of the target volume were hardly changed. CONCLUSION: In radiotherapy treatment planning for esophageal cancer patients, the skin dose can be significantly reduced using the skin dose limiting technique, and the impact on the dose to target volume and OARs is little, this technique can be used in most radiotherapy treatment planning.

13.
Mol Cancer ; 19(1): 5, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910827

RESUMO

Normal hematopoiesis requires the accurate orchestration of lineage-specific patterns of gene expression at each stage of development, and epigenetic regulators play a vital role. Disordered epigenetic regulation has emerged as a key mechanism contributing to hematological malignancies. Histone deacetylases (HDACs) are a series of key transcriptional cofactors that regulate gene expression by deacetylation of lysine residues on histone and nonhistone proteins. In normal hematopoiesis, HDACs are widely involved in the development of various lineages. Their functions involve stemness maintenance, lineage commitment determination, cell differentiation and proliferation, etc. Deregulation of HDACs by abnormal expression or activity and oncogenic HDAC-containing transcriptional complexes are involved in hematological malignancies. Currently, HDAC family members are attractive targets for drug design, and a variety of HDAC-based combination strategies have been developed for the treatment of hematological malignancies. Drug resistance and limited therapeutic efficacy are key issues that hinder the clinical applications of HDAC inhibitors (HDACis). In this review, we summarize the current knowledge of how HDACs and HDAC-containing complexes function in normal hematopoiesis and highlight the etiology of HDACs in hematological malignancies. Moreover, the implication and drug resistance of HDACis are also discussed. This review presents an overview of the physiology and pathology of HDACs in the blood system.

14.
J Exp Clin Cancer Res ; 39(1): 7, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918742

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in the progression of various cancers and affect the response to radiotherapy. This study focused on clarifying the underlying mechanism by which lncTUG1 affects the radiosensitivity of esophageal squamous cell carcinoma (ESCC). METHODS: lncTUG1, miR-144-3p and MET expression levels were detected in ESCC tissues and cells by qRT-PCR. Western blotting was used to examine the protein levels of MET, p-AKT and EGFR. The dual-luciferase reporter system and RNA immunoprecipitation (RIP) assays were used to confirm the interaction between lncTUG1 and miR-144-3p or miR-144-3p and MET. MTT, colony formation and flow cytometry assays were applied to examine the behavioral changes in EC9706 and KYSE30 cells. RESULTS: lncTUG1 was upregulated in ESCC cells and tissues, and lncTUG1 expression was associated with an advanced pathological stage. The bioinformatics analysis revealed that lncTUG1 could specifically bind to miR-144-3p, which was downregulated in ESCC. There was a negative correlation between lncTUG1 and miR-144-3p. LncTUG1 inhibition retarded proliferation and colony formation and induced apoptosis in ESCC cells. Moreover, lncTUG1 knockdown dramatically improved the effect of radiotherapy on ESCC development both in vivo and in vitro. Furthermore, MET was revealed as a downstream target of miR-144-3p and is downregulated by it. LncTUG1 promoted the progression of ESCC and elevated radiotherapy resistance in ESCC cells, accompanied by a high level of MET expression. Moreover, we found that knockdown of lncTUG1 enhanced the radiosensitivity of ESCC cells via the p-AKT signaling pathway. CONCLUSION: Our results indicate that lncTUG1 enhances the radiotherapy resistance of ESCC by lowering the miR-144-3p level and modulating the MET/EGFR/AKT axis.

15.
J Exp Bot ; 71(3): 1067-1077, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31638649

RESUMO

Plant growth is significantly altered in response to submergence stress. However, the molecular mechanisms used by seedlings in response to this stress, especially for hypocotyl growth, are largely unknown in terrestrial plants such as Arabidopsis thaliana. The microtubule cytoskeleton participates in plant cell growth, but it remains unclear whether submergence-mediated plant growth involves the microtubule cytoskeleton. We demonstrated that in Arabidopsis submergence induced underwater hypocotyl elongation through the activation of ethylene signaling, which modulated cortical microtubule reorganization. Submergence enhanced ethylene signaling, which then activated and stabilized its downstream transcription factor, phytochrome-interacting factor 3 (PIF3), to promote hypocotyl elongation. In particular, the regulation of microtubule organization was important for this physiological process. Microtubule-destabilizing protein 60 (MDP60), which was previously identified as a downstream effector of PIF3, played a positive role in submergence-induced hypocotyl elongation. Submergence induced MDP60 expression through ethylene signaling. The effects of submergence on hypocotyl elongation and cortical microtubule reorganization were suppressed in mdp60 mutants. These data suggest a potential mechanism by which submergence activates ethylene signaling to promote underwater hypocotyl elongation via alteration of the microtubule cytoskeleton in Arabidopsis.

16.
Environ Microbiol ; 22(1): 229-242, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31650666

RESUMO

Polymalic acid (PMA) is a novel biopolymer produced by the polyextremotolerant fungus Aureobasidium pullulans. In this study, a GATA-family transcriptional factor, Gat1, which regulates nitrogen uptake and PMA biosynthesis, was investigated. PMA production increased to 11.2% in the mutant overexpressing gat1 but decreased to 49.1% of the PMA titre when gat1 was knocked out from the genome of A. pullulans. Comparative transcriptome analysis of wild-type and mutant strains (∆gat1 and OE::gat1) revealed that 23 common differentially expressed genes were related to oxidative phosphorylation, ribosome biogenesis, and nitrogen metabolism. Under nitrogen-limited stress, regardless of the preferred nitrogen (glutamine, Gln) or non-preferred nitrogen (proline, Pro), 70% of Gat1 in the cells was located in the nucleus-cytoplasm, which resulted in an increase in nitrogen uptake and PMA biosynthesis regulation. Quantitative RT-PCR revealed that glucosekinase (GLK) in the glycolytic pathway and malate synthase (MLS) in the glyoxylate shunt pathway may be cross-regulated by Gat1 and nitrogen concentration (Gln or Pro), Therefore, glk was overexpressed in mutant strain (OE::gat1), which resulted in an increased PMA titre and yield of 12.6% and 13.0% respectively. These findings indicate that Gat1 may play an important role in the dual regulation of the nitrogen and carbon metabolisms in PMA biosynthesis.

17.
J Cell Mol Med ; 24(1): 511-520, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31670476

RESUMO

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot closely linked to the pathogenesis of heart failure (HF). But the molecular signatures related to the mechanism of HF have not been systematically explored. Here, we present comprehensive proteomic analysis of EAT in HF patients and non-HF patients as controls. A total of 771 proteins were identified in liquid chromatography-tandem mass spectrometry experiments. Amongst them, 17 increased in abundance in HF and seven decreased. They were involved in HF-related processes including inflammation and oxidative stress response and lipid metabolism. Of these proteins, serine proteinase inhibitor A3 (Serpina3) levels in EAT were highly up-regulated in HF, with HF/non-HF ratio of 4.63 (P = .0047). Gene expression of Serpina3 via quantitative polymerase chain reaction was significantly increased in the HF group. ELISA analysis confirmed a significant increase in circulating plasma Serpina3 levels in the HF group (P = .004). In summary, for the first time, we describe that parts of EAT proteome may be reactive and work as modulators of HF. Our profiling provides a comprehensive basis for linking EAT with pathogenesis of HF. Understanding the role of EAT may offer new insights into the treatment of HF.

18.
Biomarkers ; 25(1): 94-99, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31762333

RESUMO

Background: Permethrin is a type of widely used pyrethroid pesticide. Although acute toxicity of permethrin has been well-characterised, the non-acute toxicity of permethrin upon long-term exposure at low dose has been seldom studied yet. The current study investigates the time-course change of the metabolomic profiles of urine following the low level long-term exposure of permethrin and identified biomarkers of the chronic toxicity of permethrin.Methods: Male Wistar rats were administrated orally with permethrin (75 mg/kg body weight/day, 1/20 LD50) daily for consecutive 90 days. The urine samples from day 30, day 60, and day 90 after the first dosing were collected and analysed by 1H NMR spectrometry. Serum biochemical analysis was also carried out.Results: Permethrin caused significant changes in the urine metabolites such as taurine, creatinine, acetate, lactate, dimethylamine, dimethylglycine, and trimethylamine-N-oxide. These biological markers indicated prominent kidney and liver toxicity induced by permethrin. However, there was no change in serum biochemical parameters for the toxicity, indicating that metabolomic approach was much more sensitive in detecting the chronic toxicity.Conclusion: The time-course alteration of metabolomic profiles of the urine based on 1H NMR reflects the progressive development of the chronic toxicity with the long-term low-level exposure of permethrin.

19.
Int J Obes (Lond) ; 44(1): 213-225, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30718820

RESUMO

OBJECTIVE: Resveratrol (RSV) is a natural polyphenol with putative anti-obesity effects; however, its mechanisms of action remain unclear due to its low bioavailability. Microbial functions in the physiology result from the microbiota-host coevolution has profoundly affected host metabolism. Here, we sought to determine how beneficial microbiome caused by RSV interventions affects antiobesity. METHODS: C57BL/6J mice were fed either standard diet (SD) or RSV (300 mg/kg/day) diet for 16 weeks. The composition of the gut microbiota was assessed by analyzing 16S rRNA gene sequences. Then, transplant the RSV-microbiota to high-fat diet (HFD)-fed mice (HFD-RSVT) to explore the function of microbiota. Body weight and food intake were monitored. Markers of lipid metabolism, inflammation, gut microbiota compostion, and intestinal barrier were determined. RESULTS: Mice treated with RSV shows a remarkable alteration in microbiota composition compared with that of SD-fed mice and is characterized by an enrichment of Bacteroides, Lachnospiraceae_NK4A136_group, Blautia, Lachnoclostridium, Parabacteroides, and Ruminiclostridium_9, collectively referred to as RSV-microbiota. We further explored whether RSV-microbiota has anti-obesity functions. Transplantation of the RSV-microbiota to high-fat diet (HFD)-fed mice (HFD-RSVT) was sufficient to decrease their weight gain and increase their insulin sensitivity. Moreover, RSV-microbiota was able to modulate lipid metabolism, stimulate the development of beige adipocytes in WAT, reduce inflammation and improve intestinal barrier function. CONCLUSIONS: Our study demonstrates that RSV-induced microbiota plays a key role in controlling obesity development and brings new insights to a potential therapy based on host-microbe interactions.

20.
Carbohydr Polym ; 228: 115370, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635728

RESUMO

Nanofiber-based materials have recently gained increasing attention in food packaging, drug delivery, and biomedical applications. In this study, a multi-nanofibers composite film was developed based on bacterial cellulose nanofiber (BCNF)/chitin nanofiber (CNF) hybridization. The nanofibers were responsible for the formation of well-dispersed curcumin (Cur) micro/nanoparticles in the nanocomposite films. The release of Cur from the films were affected by CNF and the sizes of Cur particles formed in situ. The Cur particles reduced tensile strength and increased water vapor permeability of BCNF film. However, CNF improved the mechanical strength and barrier property of the Cur/BCNF/CNF composite film. Moreover, the multi-nanofibers composite film showed excellent dynamic antioxidant capacity and antibacterial activity, as well as was capable to monitor pH change and trace amount of boric acid. Results of this study suggested that the Cur/BCNF/CNF composite film can be used as a smart and active food packaging material.


Assuntos
Celulose/química , Quitina/química , Nanofibras/química , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Curcumina/farmacologia , Decapodiformes/metabolismo , Portadores de Fármacos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Embalagem de Alimentos , Microesferas , Nanocompostos/química , Nanopartículas/química , Staphylococcus aureus/efeitos dos fármacos , Resistência à Tração
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