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1.
J Am Chem Soc ; 146(29): 20477-20493, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38982945

RESUMO

Cobalt complexes with chiral quinox ligands effectively promote the enantioselective conjugate addition of enones using aryl, heteroaryl, and alkenyl halides and sulfonates. Additionally, a cobalt complex with a strongly donating diphosphine, BenzP*, successfully catalyzes the asymmetric reductive arylation and alkenylation of α,ß-unsaturated amides. Both catalytic systems show broad scopes and tolerance of sensitive functional groups. Both reactions can be scaled up with low loadings of cobalt catalysts. Experimental results and density functional theory (DFT) calculations suggest a new mechanism of elementary 1,4-addition of aryl cobalt(I) complexes.

2.
Hepatology ; 77(1): 213-229, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35363898

RESUMO

BACKGROUND AND AIMS: Metabolism in the liver is dysregulated in obesity, contributing to various health problems including steatosis and insulin resistance. While the pathogenesis of lipid accumulation has been extensively studied, the protective mechanism against lipid challenge in the liver remains unclear. Here, we report that Src homology 3 domain binding kinase 1 (SBK1) is a regulator of hepatic lipid metabolism and systemic insulin sensitivity in response to obesity. APPROACH AND RESULTS: Enhanced Sbk1 expression was found in the liver of high-fat diet (HFD)-induced obese mice and fatty acid (FA)-challenged hepatocytes. SBK1 knockdown in mouse liver cells augmented FA uptake and lipid accumulation. Similarly, liver-specific SBK1 knockout ( Lsko ) mice displayed more severe hepatosteatosis and higher expression of genes in FA uptake and lipogenesis than the Flox/Flox ( Fl/Fl ) control mice when fed the HFD. The HFD-fed Lsko mice also showed symptoms of hyperglycemia, poor systemic glucose tolerance, and lower insulin sensitivity than the Fl/Fl mice. On the other hand, hepatic Sbk1 overexpression alleviated the high-fructose diet-induced hepatosteatosis, hyperlipidemia, and hyperglycemia in mice. White adipose tissue browning was also observed in hepatic SBK1 -overexpressed mice. Moreover, we found that SBK1 was a positive regulator of FGF21 in the liver during energy surplus conditions. Mechanistically, SBK1 phosphorylates the orphan nuclear receptor 4A1 (Nur77) on serine 344 to promote hepatic FGF21 expression and inhibit the transcription of genes involved in lipid anabolism. CONCLUSIONS: Collectively, our data suggest that SBK1 is a regulator of the metabolic adaption against obesity through the Nur77-FGF21 pathway.


Assuntos
Fígado Gorduroso , Resistência à Insulina , Proteínas Quinases , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Lipídeos , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/complicações , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares
3.
J Pharmacol Sci ; 154(2): 113-126, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38246725

RESUMO

Excessive bone resorption caused by upregulated osteoclast activity is a key factor in osteoporosis pathogenesis. Farrerol is a typical natural flavanone and exhibits various pharmacological actions. However, the role and mechanism of action of farrerol in osteoclast differentiation regulation remain unclear. This study aimed to evaluate the effects and mechanism of farrerol on the inhibition of osteoclastogenesis. Tartrate-resistant acid phosphatase staining, F-actin staining, and the pit formation assay were performed to examine the differentiation and functions of osteoclasts in vitro. The expression of proteins associated with the nuclear factor kappa B and mitogen-activated protein kinase signaling pathways was analyzed by western blotting. Dual X-ray absorptiometry, microcomputed tomography, and histopathological and immunohistochemical analyses were performed to determine the therapeutic effect of farrerol in vivo bone loss prevention. The effects of farrerol on osteoblastic bone formation were assessed using alkaline phosphatase, alizarin red S staining, and calcein-alizarin red S double labeling. Farrerol inhibited osteoclastogenesis and bone resorption in osteoclasts by suppressing nuclear factor kappa B signaling rather than mitogen-activated protein kinase signaling in vitro. Farrerol protected mice against ovariectomy-induced bone loss by inhibiting osteoclast-mediated bone resorption, instead of promoting osteoblast-mediated bone formation in vivo. The findings of the current study revealed that farrerol is a potential therapeutic agent for osteoporosis.


Assuntos
Antraquinonas , Reabsorção Óssea , Cromonas , Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Animais , Camundongos , NF-kappa B , Osteoclastos , Osteoporose Pós-Menopausa/tratamento farmacológico , Microtomografia por Raio-X , Transdução de Sinais , Osteoporose/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno , Reabsorção Óssea/tratamento farmacológico
4.
Mol Biol Rep ; 50(3): 1981-1991, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36536184

RESUMO

BACKGROUND: Fibroblast growth factors (FGFs) are key factors affecting diabetic wound healing. However, the FGF family's expression patterns in skin and wounds influenced by both diabetes and sex are still unknown. METHODS AND RESULTS: In this study, normal and Streptozotocin (STZ)-induced type 1 diabetic C57BL/6J male and female mice were used to study the FGF family's expression in non-wound skin and wounds. We found that the expression patterns of Fgfs were affected by sex in both normal and diabetic animals during wound healing. In normal control mice, sex difference had a limited effect on basal skin Fgf expressions. However, it significantly influenced Fgf expressions in wounds. Type 1 diabetes reduced basal and wound-induced skin Fgf expressions. Female mice had far lower wound-induced skin Fgf expressions in diabetic mice. In addition, sex differently influenced Fibroblast growth factors receptor (Fgfr) expression patterns of non-wound skin and wounds in both normal and diabetic mice. Moreover, female mice had a lower relative level of Fibronectin leucine-rich repeat transmembrane protein 2 (FLRT2) - a FGFR activation marker gene - in wound and blood plasma. Correspondingly, the wound areas of female animals were larger than that of male animals in the early stage of wound healing (less than 3-day injury). CONCLUSION: Our research shows that the FGF family have different expression patterns in normal and diabetic wound healing in mice of different sex. Additionally, we also provide the signatures of individual FGFs in diabetic wound healing, which deserve further investigation.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Camundongos , Feminino , Masculino , Animais , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Estreptozocina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Caracteres Sexuais , Camundongos Endogâmicos C57BL , Pele/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Glicoproteínas de Membrana/metabolismo
5.
Metab Brain Dis ; 38(5): 1613-1620, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36917427

RESUMO

Orally administered ferrous iron was previously reported to significantly improve the cognition and locomotion of patients with minimal hepatic encephalopathy (MHE). However, the metabolic mechanisms of the therapeutic effect of ferrous iron are unknown. In this study, MHE was induced in rats by partial portal vein ligation (PPVL), and was treated with ferrous sulfate. The Morris water maze was used to evaluate the cognitive condition of the rats. The metabolites observed by NMR and validated by liquid chromatography-mass spectrometry were defined as the key affected metabolites. The enzyme activities and trace element contents in the rat brains were also investigated. The Mn content was found to be increased but the ferrous iron content decreased in the cortex and striatum in MHE. Decreased oxoglutarate dehydrogenase activity and increased glutamine synthetase (GS) and pyruvate carboxylase (PC) activity were observed in the cortex of MHE rats. Decreased pyruvate dehydrogenase activity and increased GS and PC activity were observed in the striatum of MHE rats. The levels of BCAAs and taurine were significantly decreased, and the contents of GABA, lactate, arginine, aspartate, carnosine, citrulline, cysteine, glutamate, glutamine, glycine, methionine, ornithine, proline, threonine and tyrosine were significantly increased. These metabolic abnormalities described above were restored after treatment with ferrous sulfate. Pathway enrichment analysis suggested that urea cycle, aspartate metabolism, arginine and proline metabolism, glycine and serine metabolism, and glutamate metabolism were the major metabolic abnormalities in MHE rats, but these processes could be restored and cognitive impairment could be improved by ferrous sulfate administration.


Assuntos
Encefalopatia Hepática , Ratos , Animais , Encefalopatia Hepática/metabolismo , Encéfalo/metabolismo , Ácido Aspártico/metabolismo , Ácido Glutâmico/metabolismo , Ácido Láctico/metabolismo , Ferro/metabolismo , Glicina/metabolismo , Arginina , Prolina
6.
Pharmacol Res ; 185: 106468, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36167277

RESUMO

Urotensin receptor (UT) is a G-protein-coupled receptor, whose endogenous ligand is urotensin-II (U-II). Skeletal muscle mass is regulated by various conditions, such as nutritional status, exercise, and diseases. Previous studies have pointed out that the urotensinergic system is involved in skeletal muscle metabolism and function, but its mechanism remains unclear, especially given the lack of research on the effect and mechanism of fasting. In this study, UT receptor knockout mice were generated to evaluate whether UT has effects on fasting induced skeletal muscle atrophy. Furthermore, the UT antagonist palosuran (3, 10, 30 mg/kg) was intraperitoneally administered daily for 5 days to clarify the therapeutic effect of UT antagonism. Our results found the mice that fasted for 48 h exhibited skeletal muscle atrophy, accompanied by enhanced U-II levels in both skeletal muscles and blood. UT receptor knockout effectively prevented fasting-induced skeletal muscle atrophy. The UT antagonist ameliorated fasting-induced muscle atrophy in mice as determined by increased muscle strengths, weights, and muscle fiber areas (including fast, slow, and mixed types). In addition, the UT antagonist reduced skeletal muscle atrophic markers, including F-box only protein 32 (FBXO32) and tripartite motif containing 63 (TRIM63). Moreover, the UT antagonist was also observed to enhance PI3K/AKT/mTOR while inhibiting autophagy signaling. In summary, our study provides the first evidence that UT antagonism may represent a novel therapeutic approach for the treatment of fasting-induced skeletal muscle atrophy.


Assuntos
Músculo Esquelético , Atrofia Muscular , Receptores Acoplados a Proteínas G , Urotensinas , Animais , Camundongos , Jejum , Camundongos Knockout , Músculo Esquelético/patologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/patologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Urotensinas/metabolismo
7.
Biometals ; 35(5): 935-953, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35857253

RESUMO

To investigate the metabolic changes in type C hepatic encephalopathy (CHE) rats after reducing manganese (Mn) intake. A total of 80 Sprague-Dawley rats were divided into control group and CHE groups (induced by intraperitoneal injection of thioacetamide at a dose of 250 mg/kg of body weight twice a week for 6 weeks). CHE rats were subdivided into 1Mn group (fed a standard diet, with 10 mg Mn/kg feed), 0.5Mn group (half-Mn diet), 0.25Mn group (quarter-Mn diet) and 0Mn group (no-Mn diet) for 4 to 8 weeks. Morris water maze (MWM), Y maze and narrow beam test (NBT) were used to evaluate cognitive and motor functions. Blood ammonia, brain Mn content, the number of GS-positive cells, and glutamine synthetase (GS) activity were measured. The metabolic changes of CHE rats were investigated using hydrogen-nuclear magnetic resonance and mass spectrometry. Multivariate statistical analysis was used to analyze the results. Significantly decreased numbers of entries in target area of MWM and Y maze, longer NBT latency and total time, higher blood ammonia, brain Mn content and GS activity were found in CHE rats. After reducing Mn intake, CHE rats had better behavioral performance, significantly lower blood ammonia, brain Mn content and GS activity. The main up-regulated metabolites were Ala, GABA, Glu, Gln, Lac, Tyr, Phe in 1Mn rats. After reducing Mn intake, metabolites returned to normal level at different degrees. Reducing Mn intake could reduce brain Mn content and blood ammonia, regulate GS activity and amino acid metabolism, ultimately improve behavioral performance in CHE rats.


Assuntos
Encefalopatia Hepática , Aminoácidos/metabolismo , Amônia/metabolismo , Animais , Glutamato-Amônia Ligase/metabolismo , Encefalopatia Hepática/induzido quimicamente , Encefalopatia Hepática/metabolismo , Encefalopatia Hepática/psicologia , Hidrogênio , Espectroscopia de Ressonância Magnética , Manganês/metabolismo , Ratos , Ratos Sprague-Dawley , Tioacetamida , Ácido gama-Aminobutírico
8.
Molecules ; 27(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36557826

RESUMO

The urotensin receptor (UT receptor), a G-protein-coupled receptor mediating urotensin-II and urotensin-II-related peptide signaling in the urotensinergic system, has multiple pharmacological activities. However, there is no drug targeting the UT receptor currently in clinical use, and the discovery of new leads is still important. The complete crystal structure of the UT receptor has not yet been resolved and a screening strategy combining multiple methods can improve the accuracy and efficiency of drug screening. This study aimed to identify novel UT receptor agonists using a combination of docking-based, pharmacophore-based, and cell-based drug screening. First, the three-dimensional structures of the UT receptor were constructed through single-template, multi-template homologous modeling and threading strategies. After structure evaluation and ligand enrichment analysis, a model from the threading modeling was selected for docking-based virtual screening based on stepwise filtering, and 1368 positive compounds were obtained from our compound library. Second, the pharmacophore models were constructed using known ligands targeting the UT receptor for pharmacophore-based virtual screening. A model was selected after model validation, and 300 positive compounds were retrieved. Then, after intersecting the results of two different virtual screening methods with 570 compound entities from our primary screening, 14 compounds were obtained. Finally, three hits were obtained after in vitro confirmation. Furthermore, preliminary evaluation of the hits showed that they influenced glucose consumption. In summary, by integrating docking-based, pharmacophore-based, and in vitro drug screening, three new agonists targeting the UT receptor were identified which may serve as promising therapeutic agents for urotensinergic system disorders.


Assuntos
Farmacóforo , Urotensinas , Simulação de Dinâmica Molecular , Receptores Acoplados a Proteínas G , Ligantes , Simulação de Acoplamento Molecular
9.
J Proteome Res ; 20(8): 3875-3888, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34270263

RESUMO

Once protein synthesis is excessive or misfolded protein becomes aggregated, which eventually overwhelms the capacity of the endoplasmic reticulum (ER), a state named ER stress would be reached. ER stress could affect many tissues, especially the liver, in which nonalcoholic fatty liver disease, liver steatosis, etc. have been reported relative. However, there is still a lack of systematic insight into ER stress in the liver, which can be obtained by integrating metabolomics and transcriptomics of the tissue. Here, tunicamycin was utilized to induce ER stress in C57BL/6N mice. Microarray and untargeted metabolomics were performed to identify the genes and metabolites significantly altered in liver tissues. Surprisingly, apart from the predictable unfolded protein response, liver lipid, arginine, and proline metabolisms were affirmed to be related to ER stress. Also, the ketone body metabolism changed most prominently in response to ER stress, with few studies backing. What is more, succinate receptor 1 (Sucnr1) may be a novel marker and therapeutical target of liver ER stress. In this study, the combination of the metabolome and transcriptome provided reliable information about liver pathological processes, including key relative pathways, potential markers, and targets involved in ER stress of the liver.


Assuntos
Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Animais , Estresse do Retículo Endoplasmático/genética , Cetonas , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transcriptoma
10.
Pharmacol Res ; 172: 105807, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34389456

RESUMO

Skeletal muscle is a crucial tissue for movement, gestural assistance, metabolic homeostasis, and thermogenesis. It makes up approximately 40% of the total body weight and 50% of total protein. However, several pathological abnormalities (e.g., chronic diseases, cancer, long-term infection, aging) can induce an imbalance in skeletal muscle protein synthesis and degradation, which triggers muscle wasting and even leads to atrophy. Skeletal muscle atrophy is characterized by weakening, shrinking, and decreasing muscle mass and fiber cross-sectional area at the histological level. It manifests as a reduction in force production, easy fatigue and decreased exercise capability, along with a lower quality of life. Mechanistically, there are several pathophysiological processes involved in skeletal muscle atrophy, including oxidative stress and inflammation, which then activate signal transduction, such as the ubiquitin proteasome system, autophagy lysosome system, and mTOR. Considering the great economic and social burden that muscle atrophy can inflict, effective prevention and treatment strategies are essential but still limited. Exercise is widely acknowledged as the most effective therapy for skeletal muscle atrophy; unfortunately, it is not applicable for all patients. Several active substances for skeletal muscle atrophy have been discovered and evaluated in clinical trials, however, they have not been marketed to date. Knowledge is being gained on the underlying mechanisms, highlighting more promising treatment strategies in the future. In this paper, the mechanisms and treatment strategies for skeletal muscle atrophy are briefly reviewed.


Assuntos
Músculo Esquelético/patologia , Atrofia Muscular , Animais , Humanos , Músculo Esquelético/metabolismo , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo
11.
Inorg Chem ; 60(20): 15485-15496, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34592811

RESUMO

A novel fluorescent probe based on a nitrogen-doped carbon dot (N-CD) and CdTe quantum dot (CdTe QD) platform has been constructed for H2O2/glucose detection and pH sensing. In this work, H2O2-tolerant blue fluorescence N-CDs were added to the H2O2-mediated yellow fluorescence quenching of CdTe QDs to construct a dual-color ratiometric fluorescent H2O2 probe. H2O2-induced passivated group detachment and action on deep nanocrystals promoted CdTe QD fluorescence quenching. Meanwhile, the addition of the blue fluorescent background of N-CDs sharply reflected the color change in CdTe QDs. Under the optimized experimental conditions, the platform was effectively applied to the detection of H2O2 produced by the enzymatic reaction of glucose, showing high sensitivity (limit of detection 7.86 µM) and wide linear range (26-900 µM) for glucose detection. The pH-sensing behavior of CdTe QDs and N-CDs was attributed to the displacement of a weak acid (3-mercaptopropionic acid) by a strong acid (HCl) and the acid titration process of two coexisting bases (N-CDs and NH3·H2O), respectively. The loss of passivation and doping effects led to a decrease in the fluorescence intensity of CdTe QDs and N-CDs. Moreover, utilizing the ability of bimaterial system fluorescence to pH sensing, a semiquantitative pH detection based on the linear response was developed. The pH range was analyzed by three kinds of N-CD (Fex = 440 nm) and CdTe QD (Fex = 548 nm) typical emission spectral shapes. In addition, the recovery results showed that the bimaterial system was proved to be appropriate for the assay of glucose in spiked serum samples.


Assuntos
Compostos de Cádmio/química , Corantes Fluorescentes/química , Glucose/análise , Nitrogênio/química , Pontos Quânticos/química , Telúrio/química , Concentração de Íons de Hidrogênio , Estrutura Molecular , Tamanho da Partícula
12.
Inorg Chem ; 60(15): 10899-10908, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34260206

RESUMO

Effective and selective separation of technetium from acidic nuclear liquid waste is highly desirable for partitioning and transmutation but is of significant challenge. Highly efficient extraction of pertechnetate can be achieved by taking H-bonding and electrostatic interaction combined strategy. Base on this strategy, an amine-amide ligand NTAamide(n-Oct) was employed to extract TcO4- in HNO3 solution. Using n-dodecane as a diluent, NTAamide(n-Oct) demonstrated excellent extractability and good selectivity toward TcO4- with a rapid extraction equilibrium that could be reached in less than 1 min. Its maximal loading capacity for TcO4- was almost 100 times as much as that of traditional amine extractant Aliquat-336 nitrate. Meanwhile, TcO4- could be efficiently stripped from the loaded organic phase by (NH4)2CO3 solution. Slope analysis indicated the formation of a 1:1 complex of NTAamide(n-Oct) with TcO4-. The extraction conformed to the anion exchange extraction model, as confirmed by analyses of single-crystal X-ray diffraction, 1H NMR titration, FTIR, and ESI-MS.

13.
Biometals ; 34(4): 841-854, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33928475

RESUMO

To evaluate magnetic resonance (MR) T1 mapping for quantifying brain manganese (Mn) deposition in type C hepatic encephalopathy (CHE) rats and to investigate the mechanism of magnesium sulfate (MgSO4) therapy. Thirty Sprague-Dawley rats were randomly assigned into normal control group (NC, n = 6) and CHE groups (n = 24). Thioacetamide (TAA) was used for modeling CHE rats. CHE groups were further divided into 4 subgroups: TAA group, MgSO4 low dose (Mg-L) group, MgSO4 high dose (Mg-H) group and deionized water (DW) group (n = 6 for each group). TAA, Mg-L, Mg-H and DW groups were received intraperitoneal injections of 250 mg TAA/kg, twice a week for 8 weeks. Mg-L and Mg-H groups were orally received MgSO4 of 124 and 248 mg/kg daily, respectively, for another 8 weeks (without TAA). MR T1 mapping was performed in NC, TAA, Mg-L, Mg-H and DW groups at various time points. T1 value and Mn content in basal ganglia, hippocampus, cerebral cortex and cerebellum were evaluated. Morris water maze (MWM) and narrow beat test (NBT) were utilized to evaluate rats' learning, memory and motor ability. Contents of interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and calcium-binding adaptor 1 protein (Iba1) were evaluated. Reduced T1 values in basal ganglia, hippocampus and cerebral cortex (P < 0.01, P < 0.05 and P < 0.05, respectively); increased Mn content in basal ganglia, hippocampus and cerebral cortex (all P < 0.05); reduced times of head contacting with region of interest (ROI), reduced times of entrance into the target quadrant (both P < 0.05); increased NBT total time (P < 0.05); increased brain contents of IL-6 (P < 0.001), TNF-α (P < 0.01) and over-expression of Iba1 were found in TAA group compared to NC group. After treated by MgSO4, increased T1 value and reduced Mn content in basal ganglia, hippocampus and cerebral cortex (all P < 0.01); increased times of head contacting with ROI, increased times of entrance into the target quadrant (both P < 0.05); reduced NBT total time (P < 0.01); reduced brain content of IL-6, TNF-α (both P < 0.05) and reduced expression of Iba1 were found. T1 values were negatively correlated with Mn contents in basal ganglia (r = - 0.834, P < 0.01), hippocampus (r = - 0.739, P < 0.05), cortex (r = - 0.801, P < 0.05) and cerebellum (r = - 0.788, P < 0.05). T1 mapping could quantify brain Mn deposition in CHE rats. MgSO4 could improve cognition and motor ability of CHE rats by reducing brain Mn deposition, alleviating neurological inflammation and achieve the effective therapy for CHE. Mn may participate in the pathogenesis of CHE through neuroinflammation.


Assuntos
Encéfalo/metabolismo , Encefalopatia Hepática/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Manganês/metabolismo , Animais , Feminino , Encefalopatia Hepática/metabolismo , Sulfato de Magnésio/administração & dosagem , Espectroscopia de Ressonância Magnética , Ratos , Ratos Sprague-Dawley
14.
Mikrochim Acta ; 189(1): 8, 2021 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862927

RESUMO

An ionic liquid-based dispersive liquid-liquid microextraction (IL-DLLME) combined with magnetic solid-phase extraction (MSPE) was developed for extraction of quinolones (quinolones) from honey and milk prior to high-performance liquid chromatography (HPLC) analysis. 1-Butyl-3-methylimidazolium hexafluorophosphate was used as the extraction solvent and an effective adsorbent based on chitosan modified magnetic core-shell functionalized multi-walled carbon nanotube (MWCNTs-Fe3O4@SiO2-CS) nanoparticles was used to assist IL to adsorb quinolone residues in honey and milk samples. Extraction conditions were optimized through one-factor-at-a-time and response surface methodology using a Box-Behnken design. Under optimum conditions satisfactory linearity (R2 > 0.999) and high sensitivity (method limits of quantification were 4-8 µg kg-1 or µg L-1 in honey or milk samples) was achieved. The recoveries of quinolones in honey and milk ranged from 81.2 to 109%. Based on this study, the proposed method was employed for the determination of antibiotic residues in honey and milk samples.

15.
Nanotechnology ; 31(32): 325703, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32315995

RESUMO

Electromagnetic (EM) wave absorbing materials have been a research hotspot in materials science and related technical fields in recent years. Finding lightweight, efficient, and broadband electromagnetic wave absorbing materials has always been a very challenging subject. Herein, we successfully prepared Co3O4-WS2 hybrid nanosheets with heterostructures, which excellent combine the advantages of magnetic property of Co3O4 and dielectric property of WS2. By the electromagnetic synergy effect, maximum RL is up to -61.1 dB at 1.9 mm, and the bandwidth exceeds 5 GHz. Such highly efficient microwave absorption is attributed to not only the electromagnetic synergy effect, but the dipole polarization as well as conduction loss. These results show that the obtained Co3O4-WS2 is an excellent EM wave absorbing material and can be used as a candidate for advanced EM wave absorbing materials in the fields such as commerce, military and aerospace in future.

16.
Nanomedicine ; 27: 102196, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32272233

RESUMO

Bone-targeted therapies have been the choice of treatments for cancer metastases in bone to minimize skeletal morbidity and preserve patients' quality of life. Rhein is of particular interest due to its high bone affinity. Here we reported a novel Rhein- polyethylene glycol (PEG)-nano hydroxyapatite (nHA) conjugate to deliver doxorubicin (DOX) and Phosphorus-32 (32P) simultaneously for enhanced cancer chemo-radiotherapy. The synthetic Rhein-PEG-nHA conjugates were sphere in shape with an average diameter of ~120 nm. Their morphology, drug release and bone affinity were confirmed in vitro. The release profiles of DOX depend on pH condition, but 32P exhibited good stability. Rhein-PEG-nHA also showed high bone affinity in vivo, and the tumor volume decreased after the DOX@Rhein-PEG-nHA and 32P@Rhein-PEG-nHA treatments. Most importantly, the DOX/32P@Rhein-PEG-nHA showed the strongest inhibition on the growth of bone metastases of breast cancer. We revealed the potential of Rhein-PEG-nHA in combined chemo-radiation treatment for bone metastases of breast cancer.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Sistemas de Liberação de Medicamentos , Animais , Antraquinonas/química , Antraquinonas/farmacologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Durapatita/química , Durapatita/farmacologia , Feminino , Humanos , Imunoconjugados/química , Imunoconjugados/farmacologia , Camundongos , Metástase Neoplásica , Radioisótopos de Fósforo/química , Radioisótopos de Fósforo/farmacologia , Polietilenoglicóis/química , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Mater Sci Mater Med ; 31(5): 47, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32390082

RESUMO

To meet the different application requirements in various fields, hydroxyapatite (HA) hollow microspheres with different surface charge were synthesized successfully by biomimetic method using Ca(NO3)2·4H2O and (NH4)2HPO4 in the presence of polyethylene glycol (PEG). Scanning electron microscopy (SEM), High-resolution TEM (HRTEM), X-ray powder diffraction (XRD), and Zeta PALS were used to characterize the obtained samples. The results indicated that the concentration of PEG and temperature significantly affect the morphology of the obtained samples. After incubation for 5 d, the HA hollow microspheres with positive surface charge, HA spherical nanoparticles with surface charge close to zero and calcium deficiency HA (d-HA) hollow microspheres with negative surface charge were obtained respectively in the presence of 5% PEG, 6% PEG and 7% PEG at 15 °C. Brunauer-Emmett-Teller (BET) revealed that the specific surface area of HA hollow microspheres reached 98.50 m2/g, while that of HA spherical nanoparticles were only 4.12 m2/g, hollow microspheres show a better application prospect. The possible formation mechanism was also discussed. Ca/P molar ratio >1.67, the surface charge of HA hollow microspheres inclines to be positive. Ca/P molar ratio <1.67, the surface charge of d-HA hollow microspheres tends to be negative.


Assuntos
Durapatita/química , Microesferas , Biomimética , Sistemas de Liberação de Medicamentos , Microscopia Eletrônica de Varredura , Nanopartículas/química , Polietilenoglicóis , Propriedades de Superfície , Difração de Raios X
18.
Biochem Biophys Res Commun ; 514(2): 407-414, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31056256

RESUMO

Skeletal muscle secretes myokines, which are involved in metabolism and muscle function regulation. The role of fasting on myokine expression in skeletal muscle is largely unknown. In this study, we used gastrocnemius skeletal muscle RNA sequencing data from fasting male mice in the Gene Expression Omnibus (GEO) database. Adopted male and female C57BL/6J mice that fasted for 24 h were included to examine the effect of fasting on myokine expression in slow-twitch soleus and fast-twitch tiabialis anterior (TA) skeletal muscle. We found that fasting significantly affected many myokines in muscle. Fasting reduced Fndc5 and Igf1 gene expression in soleus and TA muscles in both male and female mice without muscle phenotype or gender differences, but Il6, Mstn and Erfe expression was influenced by fasting with fibre type- and gender-dependent effects. Fasting also induced muscle atrophy marker genes Murf1 and Fbxo32 and reduced myogenesis factor Mef2 expression without muscle fibre or gender differences. We further found that the expression of transcription factors Pgc1α, Pparα, Pparγ and Pparδ had muscle fibre type-dependent effects, and the expression of Pgc1α and Pparα had gender-dependent effects. The sophisticated expression pattern of myokines would partially explain the complicated cross-talk between skeletal muscle and other organs in different genders and muscles phenotypes, and it is worth further investigation.


Assuntos
Citocinas/genética , Jejum/fisiologia , Regulação da Expressão Gênica , Músculo Esquelético/metabolismo , Caracteres Sexuais , Animais , Citocinas/biossíntese , Feminino , Fibronectinas/genética , Fator de Crescimento Insulin-Like I/genética , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/classificação , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Miostatina/genética , Fenótipo , Fatores de Transcrição/genética
19.
Biomed Microdevices ; 21(3): 54, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31203429

RESUMO

Aptamers have been widely used to recognize and capture their targets in sensitive detection applications, such as in detections of circulating tumor cells. In this study, we investigate the effects of different lengths of oligo-T spacers on surface tethered sgc8 aptamers and their target capturing performances. To achieve this, sgc8 aptamers were immobilized onto microfluidic channel surfaces via oligo-T spacers of different lengths, and the target capturing performances of these immobilized aptamers were studied using CCRF-CEM cells. We demonstrate that the capturing performances of the immobilized aptamers were significantly affected by steric hindrance. Our results also show that aptamers immobilized on surfaces via spacers of ten Ts demonstrated the best cell capturing performances; aptamers with either too short or too long oligo-T spacers showed reduced cell capturing performances. Therefore it can be concluded that spacer optimizations are critically important for surface tethered aptamers that are commonly used in microfluidic devices for sensitive target sensing and detections.


Assuntos
Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Separação Celular/instrumentação , Dispositivos Lab-On-A-Chip , Aptâmeros de Nucleotídeos/genética , Sequência de Bases , Linhagem Celular Tumoral , Dimetilpolisiloxanos/química , Humanos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Nylons/química , Propriedades de Superfície
20.
Nanotechnology ; 30(44): 445708, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31349245

RESUMO

Rational structure design of microwave absorption material is extremely significant from the perspectives of enhancing the electromagnetic microwave absorption (EMA) performance and adapting to cost-effective and sustainable industrial applications. Here, reduced graphene oxides (rGOs) with curl structures derived from corn stover are applied for the absorption of electromagnetic waves. The results suggest that biomass-rGO show the maximum reflection loss of -51.7 dB and an effective absorption bandwidth 13.5 GHz (4.5-18 GHz) at a thickness of 3.25 mm, implying the unique critical role of the microstructure in adjusting the EMA performance. Moreover, the successful conversion of waste biomass into widely used electromagnetic wave absorbing materials could solve the problems of environmental pollution caused by straw burning.

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