Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 494
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-36635397

RESUMO

Mitochondrial pyruvate carriers (MPCs), located in the inner membrane of mitochondria, are essential carriers for pyruvate to enter mitochondria. MPCs regulate a wide range of intracellular metabolic processes, such as glycolysis, the tricarboxylic acid cycle (TCA cycle), fatty acid metabolism, and amino acid metabolism. However, the metabolic regulation of MPCs in macrofungi is poorly studied. We studied the role of MPCs in Ganoderma lucidum (GlMPC) on ganoderic acid (GA) biosynthesis regulation in G. lucidum. In this study, we found that the mitochondrial/cytoplasmic ratio of pyruvate was downregulated about 75% in GlMPC1- and GlMPC2-silenced transformants compared with wild type (WT). In addition, the GA content was 17.72 mg/g and increased by approximately 50% in GlMPC1- and GlMPC2-silenced transformants compared with WT. By assaying the expression levels of three key enzymes and the enzyme activities of isocitrate dehydrogenase (IDH) and α-ketoglutarate dehydrogenase (α-KGDH) of the TCA cycle in GlMPC1- and GlMPC2-silenced transformants, it was found that the decrease in GlMPCs activity did not significantly downregulate the TCA cycle rate, and the enzyme activity of IDH increased by 44% compared with WT. We then verified that fatty acid ß-oxidation (FAO) supplements the TCA cycle by detecting the expression levels of key enzymes involved in FAO. The results showed that compared with WT, the GA content was 1.14 mg/g and reduced by approximately 40% in co-silenced transformants. KEY POINTS: • GlMPCs affects the distribution of pyruvate between mitochondria and the cytoplasm. • Acetyl-CoA produced by FAO maintains the TCA cycle. • Acetyl-CoA produced by FAO promotes the accumulation of GA.

2.
Appl Bionics Biomech ; 2023: 7283835, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36644768

RESUMO

In order to impprove the protective effect of the automotive energy absorption (EA) box, the design of the reentrant bioinspired EA box is proposed, that is, novel bioinspired structures are inserted into the original EA box to improve the EA effect of the box. The improved bionic structures with curvature are designed according to the spider web: honeycomb structure (HS), arc-honeycomb structure (AHS), negative Poisson structure (PS), and arc negative Poisson structure (APS). A new bionic automobile energy absorbing box is constructed by combining with automobile energy absorbing box. Experiments and simulations further verify excellent mechanical properties of bionic structures. The results show that EA of AHS and APS is 117.2% and 105.8% of HS and PS. Their specific energy absorption is 112.2% and 102.7% of HS and PS. HS EA box structure, AHS energy absorption box structure, PS energy absorption box structure, and APS energy absorption box structure are 114.2%, 117%, 109.2%, and 116.2% higher than traditional EA box structures, respectively. The excellent characteristics of biological structures can provide ideas for structural design objectives of engineering applications and greatly simplify the process of optimal design.

3.
Chem Commun (Camb) ; 59(3): 346-349, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36514971

RESUMO

The designed synthesis of chiral luminescent molecules with excellent circularly polarized luminescence (CPL) performance and high quantum yield (QY) levels has attracted great interest but remains very challenging. Herein, we report three pairs of chiral europium-titanium-oxo clusters featuring both modest CPL characteristics and high QY levels (up to 79%), which can be regulated by switching between different ligand substituents.


Assuntos
Európio , Titânio , Luminescência
4.
Cell Stem Cell ; 30(1): 69-85.e7, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36574771

RESUMO

N6-methyladenosine (m6A) is a common chemical modification for mammalian mRNA and exhibits high dynamics in various biological processes. However, dynamics of m6A RNA methylome during leukemogenesis remains unknown. Here, we delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development and identify PRMT6 as a key for maintaining AML stem cells. We observe an obvious change in m6A methylome during leukemogenesis and find that protein arginine methyltransferase PRMT6 and m6A reader IGF2BP2 maintain the function of human and murine leukemia stem cells (LSCs). Genetic deletion or pharmacological inhibition of PRMT6 damages AML development and LSC function. Mechanistically, IGF2BP2 stabilizes PRMT6 mRNA via m6A-mediated manner, which catalyzes H3R2me2a and suppresses lipid transporter MFSD2A expression. PRMT6 loss upregulates MFSD2A expression that increases docosahexaenoic acid levels and impairs LSC maintenance. Collectively, our findings reveal a critical role of PRMT6-MFSD2A signaling axis in AML development and provide a therapeutic strategy for targeting LSCs.


Assuntos
Leucemia Mieloide Aguda , RNA , Humanos , Animais , Camundongos , RNA/metabolismo , Epigenoma , RNA Mensageiro/metabolismo , Células-Tronco Neoplásicas/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Lipídeos , Mamíferos/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Nucleares/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo
5.
Nat Commun ; 13(1): 7458, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36460668

RESUMO

Fast screening of enzyme variants is crucial for tailoring biocatalysts for the asymmetric synthesis of non-natural chiral chemicals, such as amines. However, most existing screening methods either are limited by the throughput or require specialized equipment. Herein, we report a simple, high-throughput, low-equipment dependent, and generally applicable growth selection system for engineering amine-forming or converting enzymes and apply it to improve biocatalysts belonging to three different enzyme classes. This results in (i) an amine transaminase variant with 110-fold increased specific activity for the asymmetric synthesis of the chiral amine intermediate of Linagliptin; (ii) a 270-fold improved monoamine oxidase to prepare the chiral amine intermediate of Cinacalcet by deracemization; and (iii) an ammonia lyase variant with a 26-fold increased activity in the asymmetric synthesis of a non-natural amino acid. Our growth selection system is adaptable to different enzyme classes, varying levels of enzyme activities, and thus a flexible tool for various stages of an engineering campaign.


Assuntos
Aminas , Aminoácidos , Monoaminoxidase , Transaminases/genética , Cinacalcete
6.
Materials (Basel) ; 15(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36556678

RESUMO

Coal gasification slag is an inevitable by-product of the coal gasification process. This paper explored the feasibility of using activators (calcium hydroxide, sodium hydroxide, calcium sulfate, sodium sulfate) to promote the pozzolanic activity of milled coal gasification coarse slags (MCS), and analyzed the effect of alkali and sulfate activators on the hydration characteristic of cement-based materials containing MCS. Coal gasification slags with ignition lossses more than 15% were removed and the remaining slags were considered as cementitious material after milling. Scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and hydration heat tests were employed to analyze the hydration mechanism of the samples. Besides, the compressive strength values of cement mortars with MCS and activators were evaluated. The results showed that calcium hydroxide was conductive to the formation of hydration products and its crystallization could contribute to the strength improvement of the sample. Calcium sulfate mainly participated in the hydration process of cement to form ettringite (AFt) phases. Sodium hydroxide could accelerate the dissolution of active mineral phases of MCS, resulting in the pozzolanic activity being enhanced. Moreover, sodium sulfate could not only increase the formation of AFt phases, but also improved the alkalinity in sample to facilitate the production of gels. Among them, a better promotion effect could be obtained from the combined application of calcium hydroxide and sodium sulfate. In addition, the compressive strength values of cement mortars containing MCS tended to increase when activators were used. The sample activated by calcium hydroxide and sodium sulfate exhibited the highest strength, increasing by 18.55% at 28 days compared with the sample without an activator.

7.
ACS Catal ; 12(24): 15259-15270, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36570084

RESUMO

TfCa, a promiscuous carboxylesterase from Thermobifida fusca, was found to hydrolyze polyethylene terephthalate (PET) degradation intermediates such as bis(2-hydroxyethyl) terephthalate (BHET) and mono-(2-hydroxyethyl)-terephthalate (MHET). In this study, we elucidated the structures of TfCa in its apo form, as well as in complex with a PET monomer analogue and with BHET. The structure-function relationship of TfCa was investigated by comparing its hydrolytic activity on various ortho- and para-phthalate esters of different lengths. Structure-guided rational engineering of amino acid residues in the substrate-binding pocket resulted in the TfCa variant I69W/V376A (WA), which showed 2.6-fold and 3.3-fold higher hydrolytic activity on MHET and BHET, respectively, than the wild-type enzyme. TfCa or its WA variant was mixed with a mesophilic PET depolymerizing enzyme variant [Ideonella sakaiensis PETase (IsPETase) PM] to degrade PET substrates of various crystallinity. The dual enzyme system with the wild-type TfCa or its WA variant produced up to 11-fold and 14-fold more terephthalate (TPA) than the single IsPETase PM, respectively. In comparison to the recently published chimeric fusion protein of IsPETase and MHETase, our system requires 10% IsPETase and one-fourth of the reaction time to yield the same amount of TPA under similar PET degradation conditions. Our simple dual enzyme system reveals further advantages in terms of cost-effectiveness and catalytic efficiency since it does not require time-consuming and expensive cross-linking and immobilization approaches.

8.
Front Microbiol ; 13: 1020977, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36519162

RESUMO

Celiac disease (CD) is an autoimmune small bowel disease. The pattern of gut microbiota is closely related to dietary habits, genetic background, and geographical factors. There is a lack of research on CD-related gut microbiota in China. This study aimed to use 16S rDNA sequencing and metabolomics to analyze the fecal microbial composition and metabolome characteristics in patients diagnosed with CD in Northwest China, and to screen potential biomarkers that could be used for its diagnosis. A significant difference in the gut microbiota composition was observed between the CD and healthy controls groups. At the genus level, the abundance of Streptococcus, Lactobacillus, Veillonella, and Allisonella communities in the CD group were increased (Q < 0.05). Furthermore, the abundance of Ruminococcus, Faecalibacterium, Blautia, Gemmiger, and Anaerostipes community in this group were decreased (Q < 0.05). A total of 222 different fecal metabolites were identified in the two groups, suggesting that CD patients have a one-carbon metabolism defect. Four species of bacteria and six metabolites were selected as potential biomarkers using a random forest model. Correlation analysis showed that changes in the gut microbiota were significantly correlated with changes in fecal metabolite levels. In conclusion, the patterns of distribution of gut microbiota and metabolomics in patients with CD in Northwest China were found to be unique to these individuals. This has opened up a new way to explore potential beneficial effects of supplementing specific nutrients and potential diagnostic and therapeutic targets in the future.

9.
EBioMedicine ; 86: 104340, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36356476

RESUMO

BACKGROUND: Early detection of gastric cancer (GC) remains challenging. We aimed to examine urine proteomic signatures and identify protein biomarkers that predict the progression of gastric lesions and risk of GC. METHODS: A case-control study was initially designed, covering subjects with GC and gastric lesions of different stages. Subjects were aged 40-69 years, without prior diagnosis of renal or urological diseases. We enrolled a total of 255 subjects, with 123 in the discovery stage from Linqu, China, a high-risk area for GC and 132 in the validation stage from Linqu and Beijing. A prospective study was further designed for a subset of 60 subjects with gastric lesions, which were followed for 297-857 days. FINDINGS: We identified 43 differentially expressed urine proteins in subjects with GC vs. mild or advanced gastric lesions. Baseline urinary levels of ANXA11, CDC42, NAPA and SLC25A4 were further positively associated with risk of gastric lesion progression. Three of them, except for SLC25A4, also had higher expression in GC than non-GC tissues. Integrating these four proteins showed outstanding performance in predicting the progression of gastric lesions (AUC (95% CI): 0.92 (0.83-1.00)) and risk of GC (AUC (95% CI): 0.81 (0.73-0.89) and 0.84 (0.77-0.92) for GC vs. mild or advanced gastric lesions respectively). INTERPRETATION: This study revealed distinct urine proteomic profiles and a panel of proteins that may predict the progression of gastric lesions and risk of GC. These biomarkers in a non-invasive approach may have translational significance for defining high-risk populations of GC and its early detection. FUNDING: Funders are listed in the Acknowledgement.

11.
Scand J Gastroenterol ; : 1-6, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36415137

RESUMO

BACKGROUND: Celiac disease (CD) is an autoimmune small bowel disease. Genetic susceptibility for CD is mainly determined by the human leukocyte antigen (HLA)-DQ haplotypes. The risk of CD conferred by HLA genotypes varies geographically and across populations, however, this has not yet been documented in Chinese patients with CD. AIMS: To investigate the distribution of HLA-DQ and the related risks of CD development in Northwest China. METHODS: A total of 75 CD patients and 300 healthy individuals were genotyped for HLA-DQ using the Illumina NextSeq, and the relative risks of the different genotypes were evaluated. RESULTS: In total, 68.00% of CD patients and 21.00% of controls carried HLA-DQ2.5 heterodimers (p < 0.001). We identified four CD risk gradients. Individuals carrying a double dose of DQB1*02 had the highest risk of developing CD (1:16); however, with heterozygosis (DQB1*02:02/DQB1*02:01) having the highest risk (1:9). HLA-DQ2.5 individuals with a single copy of HLA-DQB1*02, in either the cis or trans configuration, were at a medium risk (1:38). Non-DQ2.5 carriers of DQ8 or DQ2.2 were at low risk, while only carriers of DQ7.5 or DQX.5 were at very low risk. Patients with the HLA-DQ2.5 genotype had more severe mucosal damage compared with the HLA-DQ2.5 genotype negative CD patients (70.59% vs. 41.67%, p = 0.016). CONCLUSION: Genetic susceptibility to CD is highly prevalent in the Northwest Chinese population and the highest risk of developing CD was associated with the DQ2.5/DQ2.2 genotype. The DQ2.5 allele is involved in the severity of mucosal injury.

12.
J Atheroscler Thromb ; 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36436875

RESUMO

AIMS: Acute rupture or erosion of unstable atherosclerotic plaques is a major cause of adverse consequences of atherosclerotic cardiovascular disease, often leading to myocardial infarction or stroke. High uric acid (HUA) is associated with the increasing risk of cardiovascular events and death. However, the mechanism by which HUA promotes atherosclerosis and whether HUA affects plaque stability are still unclear. METHODS: We constructed an atherosclerotic Apoe-/- mouse model with HUA. The progression of atherosclerosis and plaques was determined by Oil Red O staining, hematoxylin and eosin (H&E) staining, and Masson staining. TdT-mediated dUTP nick-end labeling assay and immunohistochemistry were used to observe the changes of apoptosis and autophagy in plaques, respectively. Then, we validated the in vivo results with RAW 264.7 cell line. RESULTS: HUA promoted atherosclerosis and exacerbated plaque vulnerability, including significantly increased macrophage infiltration, lipid accumulation, enlarged necrotic cores, and decreased collagen fibers. HUA increased cell apoptosis and inhibited autophagy in plaques. In vitro results showed that HUA decreased cell viability and increased cell apoptosis in foam cells macrophages treated with oxidized low-density lipoprotein. An activator of autophagy, rapamycin, can partially reverse the increasing apoptosis. CONCLUSION: HUA promoted atherosclerosis and exacerbated plaque vulnerability, and HUA facilitates foam cell apoptosis by inhibiting autophagy.

13.
Materials (Basel) ; 15(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36431520

RESUMO

Biodegradable pure iron has gained significant interest as a biomedical material. For biodegradable implant applications, the biodegradation behavior of pure iron is important. In this work, the influence of ferrite grain size on the biodegradation rate for pure iron was studied by means of heat treatment that was annealed below the austenized temperature using as-forged pure iron. Grains were coarsened and a spectrum of ferrite grain sizes was gained by changing the annealed temperature. Biodegradation behavior was studied through weight loss tests, electrochemical measurements and microscopic analyses. Hardness (HV) and biodegradation rate (Pi or Pw) were linearly ferrite grain size-dependent: HV=58.9+383.2d-12, and Pi=-0.023+0.425d-12 or Pw=0.056+0.631d-12. The mechanism by which the role of grain size on biodegradation rate was attributed to the ferrite grain boundary traits.

14.
Materials (Basel) ; 15(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36431684

RESUMO

Dilution rate is one of most important factors influencing the microstructure and performance of the laser cladding layer. In order to obtain a reasonable dilution rate in the laser cladding layer of Inconel 625 alloy, the laser cladding layers with different Fe content were prepared on the surface of 20# steel by the laser cladding technique. The influence of Fe content on the microstructure and performance of Inconel 625 alloy cladding layer was investigated. The results indicate that with the increase in Fe content in the alloy, the grain size of the cladding layer becomes coarser, the grain orientation difference increases first and then decreases, and the grain boundary angle decreases first and then increases. The hardness, high temperature wear resistance, and high temperature corrosion resistance gradually decreased. It is concluded that the dilution rate of Fe in laser cladding Inconel 625 alloy should be under 5 wt.%.

15.
Am J Chin Med ; 50(8): 2103-2123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36309811

RESUMO

Doxorubicin (DOX) is a most common anthracycline chemotherapeutic agent; however, its clinical efficacy is limited due to its severe and irreversible cardiotoxicity. Ferroptosis, characterized by iron overload and lipid peroxidation, plays a pivotal role in DOX-induced cardiotoxicity. Resveratrol (RSV) displays cardioprotective and anticancer effects, owing to its antioxidative and anti-inflammatory properties. However, the role and mechanism of RSV in DOX-mediated ferroptosis in cardiomyocytes is unclear. This study showed that DOX decreased cell viability, increased iron accumulation and lipid peroxidation in H9c2 cells; however, these effects were reversed by RSV and ferroptosis inhibitor ferrostatin-1 (Fer-1) pre-treatment. Additionally, RSV significantly increased the cell viability of H9c2 cells treated with ferroptosis inducers Erastin (Era) and RSL3. Mechanistically, RSV inhibited mitochondrial reactive oxygen species (mtROS) overproduction and upregulated the p62-NRF2/HO-1 pathway. RSV-induced NRF2 activation was partially dependent on p62, and the selective inhibition of p62 (using p62-siRNA interference) or NRF2 (using NRF2 specific inhibitor, ML385) significantly abolished the anti-ferroptosis function of RSV. Furthermore, RSV treatment protected mice against DOX-induced cardiotoxicity, including significantly improving left ventricular function, ameliorating myocardial fibrosis and suppressing ferroptosis. Consistent with in vitro results, RSV also upregulated the p62-NRF2/HO-1 expression, which was inhibited by DOX, in the myocardium. Notably, the protective effect of RSV in DOX-mediated ferroptosis was similar to that of Fer-1 in vitro and in vivo. Thus, the p62-NRF2 axis plays a critical role in regulating DOX-induced ferroptosis in cardiomyocytes. RSV as a potent p62 activator has potential as a therapeutic target in preventing DOX-induced cardiotoxicity via ferroptosis modulation.


Assuntos
Miócitos Cardíacos , Fator 2 Relacionado a NF-E2 , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Estresse Oxidativo , Doxorrubicina/efeitos adversos
16.
Front Hum Neurosci ; 16: 1005425, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36310844

RESUMO

Introduction: Attention deficit and hyperactivity disorder (ADHD) is a common inherited disease of the nervous system whose cause(s) and pathogenesis remain unclear. Currently, the diagnosis of ADHD is mainly based on clinical experience and guidelines that have laid out some diagnostic standards. Our study aimed to apply a learning-based classification method to assist the ADHD diagnosis based on high-dimensional resting-state fMRI. Methods: Our study selected the ADHD-200 Peking dataset of resting-state fMRI, which has an ADHD patient (n = 142) group and a typically developing control (TDC) healthy control (n = 102) group. We first used Pearson and partial correlation coefficients to perform functional connectivity (FC) analysis between ROIs. Then, the Pearson and partial correlation coefficient matrices were concatenated into a dual-channel feature to build a dual data channel as input to the transfer learning neural network (TLNN) architecture. Finally, we transferred the pretrained model from the auxiliary domain to our target domain and fine-tuned it. Results: Based on the Pearson correlation coefficient, FC between ROIs was detected in 22 brain regions, including the fusiform gyrus, superior frontal gyrus, posterior superior temporal sulcus, inferior parietal lobule, anterior cingulate cortex, and parahippocampal gyrus. Based on the partial correlation coefficient, we found FC in the salient network, default network, sensory-motor network, dorsal attention network, and cerebellum network. With the TLNN architecture, we solved the problem of insufficient training data and improved the sensitivity of the classification method. When the VGG model (fine-tuned transfer strategy, 1,024 fully connected layers) was applied, the accuracy of TLNN classification ultimately reached 82%. Conclusion: Our study suggests that completing the training of the target domain by transferring the prior knowledge of the auxiliary domain is effective in solving the classification problem of small sample datasets. Based on prior knowledge of FC analysis, TLNN classification may assist ADHD diagnosis in a new way.

17.
Pak J Med Sci ; 38(7): 1802-1807, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246706

RESUMO

Objectives: To evaluate the clinical efficacy of C5V chemotherapy combined with transcatheter subcutaneous radiofrequency ablation in the treatment of children with advanced (stage III/IV) hepatoblastoma. Methods: Eighty children with advanced (Stage III/IV) hepatoblastoma were admitted in Hebei Children's Hospital from May 2019 to September 2021 randomly divided into two groups: control group and experimental group, with 40 cases in each group. Children in the control group received C5V chemotherapy, while those in the experimental group received C5V chemotherapy combined with transcatheter subcutaneous radiofrequency ablation. After treatment, the treatment effect, adverse drug reactions, AFP, ALT, AST, HBG and other indicators of the two groups were compared and analyzed. And the difference in survival rate and recurrence rate between the two groups was compared and analyzed. Results: The total efficacy of the experimental group was 67.5%, which was significantly better than 45% of the control group (p=0.04). The incidence of adverse drug reactions in the experimental group was 50%, while that in the control group was 35% (p=0.15). After treatment, AFP, ALT and AST in the experimental group were significantly lower than those in the control group, while the HBG was slightly higher than that of the control group (p=0.03). Moreover, the overall survival rate of the experimental group was significantly higher than that of the control group, and the recurrence rate was significantly lower than that of the control group. Conclusion: C5V chemotherapy combined with transcathetal subcutaneous radio fascial ablation is a safe and effective regimen for children with advanced (stage III/IV) hepatoblastoma, boasting definite efficacy and no increase in adverse reactions.

18.
Chemistry ; : e202202178, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36124833

RESUMO

Herein, we propose a rational design strategy by introducing photoactive thienyl and pyridyl groups into an AIE-active tetraarylethene skeleton to achieve highly efficient photochemistry-activated fluorescence enhancement from dominantly photo-physical aggregation-induced emission behavior, and prove that such photoactivated fluorescence enhancement is perfectly suited for superstable photocontrollable dual-mode patterning applications in both solution and solid matrix. It is found that the photoactivated fluorescence of designed AIEgen is attributed to the irreversible cyclized-dehydrogenation reaction under UV irradiation, and the oxidation product has a brighter fluorescence in both solution and solid states owning to its rigid and planar structure. The overall transformation rate of the AIEgen from its opened form to dehydrogenated form is up to nearly 100 % in a short period of UV irradiation, and the fast transformation and the stable product of this photochemical reaction guarantees super stability of photocontrolled patterning, which can be applied in photoactivated dual-mode patterning and advanced anti-counterfeiting.

20.
Front Immunol ; 13: 931087, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36177037

RESUMO

Aim: Numerous reports have demonstrated the key importance of macrophage-elicited metabolic inflammation in insulin resistance (IR). Our previous studies confirmed that hyperuricemia or high uric acid (HUA) treatment induced an IR state in several peripheral tissues to promote the development of type 2 diabetes mellitus (T2DM). However, the effect of HUA on glucose uptake and the insulin sensitivity of macrophages and its mechanism is unclear. Methods: To assess systemic IR, we generated hyperuricemic mice by urate oxidase knockout (UOX-KO). Then, glucose/insulin tolerance, the tissue uptake of 18F-fluorodeoxyglucose, body composition, and energy balance were assessed. Glucose uptake of circulating infiltrated macrophages in the liver was evaluated by glucose transporter type 4 (GLUT-4) staining. Insulin sensitivity and the insulin signaling pathway of macrophages were demonstrated using the 2-NBDG kit, immunoblotting, and immunofluorescence assays. The immunoprecipitation assay and LC-MS analysis were used to determine insulin receptor substrate 2 (IRS2) levels and its interacting protein enrichment under HUA conditions. Results: Compared to WT mice (10 weeks old), serum uric acid levels were higher in UOX-KO mice (WT, 182.3 ± 5.091 µM versus KO, 421.9 ± 45.47 µM). Hyperuricemic mice with metabolic disorders and systemic IR showed inflammatory macrophage recruitment and increased levels of circulating proinflammatory cytokines. HUA inhibited the nuclear translocation of GLUT-4 in hepatic macrophages, restrained insulin-induced glucose uptake and glucose tolerance, and blocked insulin IRS2/PI3K/AKT signaling. Meanwhile, HUA mediated the IRS2 protein degradation pathway and activated AMPK/mTOR in macrophages. LC-MS analysis showed that ubiquitination degradation could be involved in IRS2 and its interacting proteins to contribute to IR under HUA conditions. Conclusion: The data suggest that HUA-induced glucose intolerance in hepatic macrophages contributed to insulin resistance and impaired the insulin signaling pathway via IRS2-proteasome degradation.


Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Hiperuricemia , Resistência à Insulina , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Citocinas/metabolismo , Fluordesoxiglucose F18 , Glucose/metabolismo , Intolerância à Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Hiperuricemia/metabolismo , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Células de Kupffer/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Urato Oxidase , Ácido Úrico/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...