AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
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2023
·Vol. 325
·期 4
·E376
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IF 5.1
Meijuan Dong,Kun An,Li Mao
Download figureDownload PowerPointHyperuricemia (HUA) is strongly associated with the increasing prevalence of obesity, but the underlying mechanism remains elusive. Dysfunction of brown adipose tissue (BAT) could lead to obesity. However, studies on the role of HUA on BAT are lacking. Our retrospective clinical analysis showed that serum uric acid (UA) is significantly associated with BAT in humans. To investigate the role of UA in regulating BAT function, we used UA to treat primary brown adipocytes (BACs) in vitro and established HUA mice. In vitro results showed that HUA suppressed thermogenic gene expression and oxygen consumption rate. Accordingly, HUA mice exhibited lower energy expenditure and body temperature, with larger lipid droplets and lower thermogenic gene expression. These results demonstrate that HUA inhibits BAT thermogenic capacity in vitro and in vivo. To further elucidate the mechanism of UA on adipocytes, mRNA-sequencing analysis was performed and screened for “AMP-activated protein kinase (AMPK) signaling pathway” and “mitochondrial biogenesis.” Further tests in vivo and in vitro showed that the phosphorylation of AMPK was suppressed by HUA. Activation of AMPK alleviated the inhibition of AMPK phosphorylation by HUA and increased mitochondrial biogenesis, subsequently restoring the impaired BAT thermogenic capacity in vitro and vivo. Thus, we confirmed that HUA suppresses mitochondrial biogenesis by regulating AMPK, thereby inhibiting BAT thermogenic capacity. Taken together, our study identifies UA as a novel regulator of BAT thermogenic capacity, providing a new strategy to combat obesity.NEW & NOTEWORTHY To investigate the effect and mechanism of UA on BAT thermogenic capacity, we established HUA models in vitro and in vivo, and performed RNA sequencing analysis. Our results revealed that HUA suppresses mitochondrial biogenesis by regulating AMPK, thereby inhibiting BAT thermogenic capacity. Taken together, our study identifies UA as a novel regulator of BAT thermogenic capacity, providing a new strategy to combat obesity.
研究领域:
内分泌学
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代谢学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 24
·17280
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IF 5.6
Hui Li,Mingchao Wang,Kai Qu,Ruiming Xu,Haibo Zhu
It is widely recognized that macrophage cholesterol efflux mediated by the ATP-binding cassette transporter A1 (ABCA1) constitutes the initial and rate-limiting step of reverse cholesterol transport (RCT), displaying a negative correlation with the development of atherosclerosis. Although the transcriptional regulation of ABCA1 has been extensively studied in previous research, the impact of post-translational regulation on its expression remains to be elucidated. In this study, we report an AMP-activated protein kinase (AMPK) agonist called ((2R,3S,4R,5R)-3,4-dihydroxy-5-(6-((3-hydroxyphenyl) amino)-9H-purin-9-yl) tetrahydrofuran-2-yl) methyl dihydrogen phosphate (MP), which enhances ABCA1 expression through post-translational regulation rather than transcriptional regulation. By integrating the findings of multiple experiments, it is confirmed that MP directly binds to AMPK with a moderate binding affinity, subsequently triggering its allosteric activation. Further investigations conducted on macrophages unveil a novel mechanism through which MP modulates ABCA1 expression. Specifically, MP downregulates the Cav1.2 channel to obstruct the influx of extracellular Ca2+, thereby diminishing intracellular Ca2+levels, suppressing calcium-activated calpain activity, and reducing the interaction strength between calpain and ABCA1. This cascade of events culminates in the deceleration of calpain-mediated degradation of ABCA1. In conclusion, MP emerges as a potentially promising candidate compound for developing agents aimed at enhancing ABCA1 stability and boosting cellular cholesterol efflux and RCT.Keywords:ATP-binding cassette transporter A1;reverse cholesterol transport;AMP-activated protein kinase;MP;calpain-mediated degradation
研究领域:
心血管研究
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药理学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Yuwei Guan,Xue Shuai,Xiangyan Ruan,Yuejiao Wang,Yun Wei
Bovine serum albumin (BSA) is one of the most abundant proteins in serum, and its high-throughput detection is still one of the current challenges. Nitrogen‑phosphorus co-doped carbon dots (CDs) were synthesized by a hydrothermal method. Adenosine monophosphate (AMP) was used as a precursor for the synthesis of CDs, providing the required carbon, nitrogen and phosphorus sources for the CDs. It was also used as an organic bridge ligand for coordination polymers. Upon addition of the lanthanide metal ion Tb 3+ , the AMP molecules formed lanthanide coordination polymers in solution, resulting in fabrication of the novel ratiometric fluorescent probe AMP-CDs@Tb with dual emission centers. This fabricated method greatly reduced the complexity of dual-emission CDs doped with lanthanide metals. The designed ratiometric fluorescent probe only needed one precursor AMP to realize the synthesis of CDs and bound to lanthanide metal ions as an organic ligand, this probe could be used for rapid and sensitive analysis of BSA. The linear relationship was good when the concentration of BSA was 0.1 to 650 μM, and the LOD was 0.042 μM. In addition, the possible detection mechanism of BSA was explored through fluorescence lifetime and density functional theory calculations.
研究领域:
生物化学
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分析化学
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材料科学
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DOI
PubMed
高影响因子
Current Alzheimer Research
·
2020
·Vol. 17
·期 8
·735-752
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IF 3.047
Qiao Peifeng,Ma Jingxi,Wang Yangyang,Huang Zhenting,Zou Qian,Cai Zhiyou,Tang Yong
Background: Neuroinflammation plays an important role in the pathophysiological process of various neurodegenerative diseases. It is well known that curcumin has obvious anti-inflammatory effects in various neuroinflammation models. However, its effect on the modulation of microglial
polarization is largely unknown. Objective: This study aimed to investigate whether curcumin changed microglia to an anti-inflammatory M2-phenotype by activating the AMP-activated protein kinase (AMPK) signaling pathway. Methods: LPS treatment was used to establish BV2 cells and
primary microglia neuroinflammation models. The neuroinflammation mouse model was established by an intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) in the lateral septal complex region of the brain. TNF-α was measured by ELISA, and cell viability was measured by Cell
Counting Kit-8 (CCK-8). The expression of proinflammatory and anti-inflammatory cytokines was examined by Q-PCR and Western blot analysis. Phenotypic polarization of BV2 microglia was detected by immunofluorescence. Results: Curcumin enhanced AMPK activation in BV2 microglial cells in
the presence and absence of LPS. Upon LPS stimulation, the addition of curcumin promoted M2 polarization of BV2 cells, as evidenced by suppressed M1 and the elevated M2 signature protein and gene expression. The effects of curcumin were inhibited by an AMPK inhibitor or AMPK knockdown. Calmodulin-dependent
protein kinase kinase β (CaMKKβ) and liver kinase B1 (LKB1) are upstream kinases that activate AMPK. Curcumin can activate AMPK in Hela cells, which do not express LKB1. However, both the CaMKKβ inhibitor and siRNA blocked curcumin activation of AMPK in LPS-stimulated BV2 cells.
Moreover, the CaMKKβ inhibitor and siRNA weaken the effect of curcumin suppression on M1 and enhancement of M2 protein and gene expression in LPS-stimulated BV2 cells. Finally, curcumin enhanced AMPK activation in the brain area where microglia were over-activated upon LPS stimulation
in an in vivo neuroinflammation model. Moreover, curcumin also suppressed M1 and promoted M2 signature protein and gene expression in this in vivo model. Conclusion: Curcumin enhances microglia M2 polarization via the CaMKKβ-dependent AMPK signaling pathway. Additionally, curcumin
treatment was found to be neuroprotective and thus might be considered as a novel therapeutic agent to treat the neurodegenerative disease such as Alzheimer's disease, Parkinson's disease, etc.
研究领域:
神经科学
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药理学
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炎症生物学
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神经退行性疾病
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DOI
PubMed
高影响因子
ACS Nano
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2017
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IF 13.942
Da Huo,Ge Liu,Yanzhao Li,Yuxin Wang,Ge Guan,Mingcan Yang,Keyu Wei,Jingyuan Yang,Lingqin Zeng,Gang Li,Wen Zeng,Chuhong Zhu
Thrombosis is one of the biggest obstacles in the clinical application of small-diameter tissue-engineered blood vessels (TEBVs). The implantation of an unmodified TEBV will lead to platelet aggregation and further activation of the coagulation cascade, in which the high concentration of adenosine diphosphate (ADP) that is released by platelets plays an important role. Inspired by the phenomenon that endothelial cells continuously generate endogenous antiplatelet substances via enzymatic reactions, we designed a reduced graphene oxide (RGO) based dual-enzyme biomimetic cascade to successively convert ADP into adenosine monophosphate (AMP) and AMP into adenosine. We used RGO as a support and bound apyrase and 5′-nucleotidase (5′-NT) on the surface of RGO through covalent bonds, and then, we modified the surface of the collagen-coated decellularized vascular matrix with the RGO-enzyme complexes, in which RGO functions as a platform with a large open surface area and minimal diffusion barriers for substrates/products to integrate two catalytic systems for cascading reactions. The experimental results demonstrate that the two enzymes can synergistically catalyze procoagulant ADP into anticoagulant AMP and adenosine successively under physiological conditions, thus reducing the concentration of ADP. AMP and adenosine can weaken or even reverse the platelet aggregation induced by ADP, thereby inhibiting thrombosis. Adenosine can also accelerate the endothelialization of TEBVs by regulating cellular energy metabolism and optimizing the microenvironment, thus ensuring the antithrombotic function and patency of TEBVs even after the RGO-enzyme complex loses its activity.
研究领域:
生物医学工程
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材料科学
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组织工程
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止血与血栓
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DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2021
·Vol. 43
·期 5
·1264-1273
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IF 6.15
Ren Zheng-nan,Yang Jun,Zhang Meng-ya,Huang Yi-wen,Song Dong-xiao,Sun Xun,Pan Li-long,Sun Jia
Acute pancreatitis (AP), an inflammatory disorder of the pancreas, is a complicated disease without specific drug therapy. ( R )-4,6-dimethoxy-3-(4-methoxy phenyl)-2,3-dihydro-1H-indanone [( R )-TML104] is a synthesized analog of the natural product resveratrol sesquiterpenes (±) -isopaucifloral F. This study aimed to investigate the effect and underlying mechanism of ( R )-TML104 on AP. The experimental AP model was induced by caerulein hyperstimulation in BALB/c mice. ( R )-TML104 markedly attenuated caerulein-induced AP, as evidenced by decreased pancreatic edema, serum amylase levels, serum lipase levels, and pancreatic myeloperoxidase activity. In addition, ( R )-TML104 significantly inhibited the expression of pancreatic chemokines C–C motif chemokine ligand 2 and macrophage inflammatory protein-2 and the infiltration of neutrophils and macrophages. Mechanistically, ( R )-TML104 activated AMP-activated protein kinase and induced sirtuin 1 (SIRT1) expression. ( R )-TML104 treatment markedly induced the SIRT1-signal transducer and activator of transcription 3 (STAT3) interaction and reduced acetylation of STAT3, thus inhibiting the inflammatory response mediated by the interleukin 6-STAT3 pathway. The effect of ( R )-TML104 on SIRT1-STAT3 interaction was reversed by treatment with a SIRT1 inhibitor selisistat (EX527). Together, our findings indicate that ( R )-TML104 alleviates experimental pancreatitis by reducing the infiltration of inflammatory cells through modulating SIRT1.
研究领域:
药理学
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炎症
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胰腺疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
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2018
·Vol. 6
·期 7
·1923-1935
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IF 5.831
Xu Chen,Yanan Liu,Ange Lin,Na Huang,Liquan Long,Ye Gang,Jie Liu
Efflux pump system-mediated bacterial multidrug resistance is one of the main causes of antibiotic failure. Therefore, it is necessary to develop a novel nanocarrier that could effectively inhibit drug-resistant bacteria by increasing the intake and retention time of antibiotics. Herein, we constructed a pH-responsive nanocarrier (MSN@FA@CaP@FA) with double folic acid (FA) and calcium phosphate (CaP) covered on the surface of mesoporous silica (MSN) by electrostatic attraction and biomineralization, respectively. Afterward, loading the nanocomposites with ampicillin (Amp) effectively increased the uptake and reduced the efflux effect in Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by the specific targeting of FA. Moreover, Amp-MSN@FA@CaP@FA could specifically transport Amp to the bacterial infection site. Similarly, antibacterial experiments revealed that the Amp-MSN@FA@CaP@FA could significantly enhance the activity of Amp for inhibiting drug-resistant bacteria, without producing drug resistance. Additionally, the Amp-MSN@FA@CaP@FA could reduce the content of protein and inhibit the protein activity in drug-resistant bacteria, so that it destroyed the bacterial membrane and led to the bacteria death. In vivo antibacterial experiments showed that the Amp-MSN@FA@CaP@FA could effectively reduce the mortality of drug-resistant E. coli infection and promote wound healing of drug-resistant S. aureus infection. In summary, Amp-MSN@FA@CaP@FA has a potential for application in sustained-release nanostructures and to inhibit drug-resistant bacteria.
研究领域:
纳米医学
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微生物学
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药物递送系统
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DOI
PubMed
高影响因子
Chemical Engineering and Processing-Process Intensification
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2019
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IF 3.031
Yanchi Jiang,Zhongxiao Zhang,Aiwei Mu,Liu Yang,Jian Liu,Ziqi Zhao,Mengchuan Jia,Junjie Fan
Chemical absorption technology has been wildly demonstrated in industry, the absorbents have become one of the most decisive factors for the process intensification of CCS technology. In this work, two schemes about bended amine and nanofluid were adopted to develop high-performance TETA-based absorbent. A bubble reaction experimental system was established to extract key data of absorbents’ properties. An AHP model was applied by setting up characteristic matrices to determine the CO 2 capture capacities of the overall aspects. The results show that the configuration of 10 wt. %TETA + 5.0 wt. %AMP has the optimal CO 2 capture performance with the highest score of 0.763 in blended amine category. The performance of nanofluids are generally higher than the blank TETA solution, though it triggers a 0.6%–3.1% growth of Purchase cost. The AHP score increases first and then declines with the rising of nanoparticle’s mass fraction, and the highest score is given to the activator of 0.1 wt. % TiO 2 . For the configurations of nanofluids- surfactants, the citrate sodium shows a superior overall CO 2 capture performance than Triton X-100, and the reasonable mass fraction of citrate sodium is considered as 0.05 wt. % with the AHP score of 0.792.
研究领域:
化学工程
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环境科学
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材料科学
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DOI
高影响因子
AQUACULTURE
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2023
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IF 4.5
Jiali Mi,Dan Liu,Chaobin Qin,Xiao Yan,Peng Pang,Yinghao Yun,Luming Wang,Guoxing Nie
(−)-Epicatechin (EC) exhibits antioxidant effects and strengthens skeletal muscle growth and differentiation in mammals. However, there are no reports about the effects of EC in fish. This study evaluated the effects of EC on muscle antioxidant capacity, myofiber development, texture characteristics, and histomorphology were also investigated through feeding trial. 300 fish (16.27 ± 0.24 g) were fed four diets with different levels of EC (0, 100, 500, and 1000 mg/kg) for 60 days. The result showed that 1000 mg/kg EC supplementation enhanced antioxidant capacity and protein content in the muscle. Meanwhile, higher expression levels of proliferating cell nuclear antigen ( pcna ), myogenic differentiation antigen ( myod ), myogenin , myosin myosin heavy chain ( myhc ), and myosin light chain ( mylc ) were detected in the muscle of EC treatment, while the myostatin ( mstnb ) mRNA level was decreased in the EC 1000 group, the similar trends were observed in the protein expression levels of MyoD , Myogenin, MyLc ( P < 0.05). Muscle hardness and pH value were increased significantly in EC 500 and 1000 groups ( P < 0.05). Additionally, myofiber density, small-sized fiber percentage, and expression of genes related to AMP-activated protein kinase (AMPK) signaling pathway was promoted in the EC groups. These results indicated that dietary EC improved fillet quality and promoted myofiber development in Yellow River carp , which might be related to AMPK pathway.
研究领域:
水产养殖
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营养学
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分子生物学
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鱼类生理学
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产品关联
DOI
高影响因子
FOOD CHEMISTRY
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2024
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IF 8.5
Xiankang Fan,Mingzhen Liu,Zihang Shi,Tao Zhang,Lihui Du,Zhen Wu,Xiaoqun Zeng,Xiang Wu,Daodong Pan
The effects and underlying molecular mechanisms of binary probiotics ( Lactiplantibacillus plantarum subsp. plantarum CGMCC 1.5953 and Lacticaseibacillus casei CGMCC 1.5956) on the quality of wolfberry fermented beverages (WFB) were investigated. The results indicated that binary probiotics increased the number of probiotics, anthocyanin (89.92 ± 1.64 mg/L), polyphenol content (283.04 ± 3.81 µg/mL), and odor score (24.19) in WFB. Metabolomics found that they could enhance signal exchange (cyclic AMP) between binary probiotics and improve the utilization of citrulline, d -proline, d -glucose, and d -galactose through galactose metabolism and amino acid biosynthesis pathway to promote probiotics growth. Furthermore, HS-SPME-GC–MS and GS-IMS revealed that the improvement in flavor was mainly due to an increase in the content of the aromatic flavor substances 3-heptanol, glutaraldehyde, and 2-heptanone, and a decrease in the content of the off-flavor substances methyl isobutyl ketone-D and 2-undecanone. This is strategically important for the development of WFB with high probiotic content and unique flavor.
研究领域:
食品科学
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微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
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2023
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IF 4.5
Ao-Chun Yue,Xu-Dong Zhou,Hui-Ping Song,Xu-Han Liu,Ming-Jun Bi,Wei Han,Qin Li
Sulforaphane (SFN) has attracted much attention due to its ability on antioxidant, anti-inflammatory, and anti-apoptotic properties, while its functional targets and underlying mechanism of action on brain injury caused by acute carbon monoxide poisoning (ACOP) have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the mechanism of SFN in the treatment of brain damage after ACOP. In this study, the results of network pharmacology demonstrated that there were a total of 81 effective target genes of SFN and 36 drug–disease targets, which were strongly in connection with autophagy–animal signaling pathway, drug metabolism, and transcription disorders in cancer. Upon the further biological function and KEGG signaling pathway enrichment analysis, a large number of them were involved in neuronal death, reactive oxygen metabolic processes and immune functions. Moreover, based on the results of bioinformatics prediction associated with multiple potential targets and pathways, the AMP-activated protein kinase (AMPK) signaling pathway was selected to elucidate the molecular mechanism of SFN in the treatment of brain injury caused by ACOP. The following molecular docking analysis also confirmed that SFN can bind to AMPKα well through chemical bonds. In addition, an animal model of ACOP was established by exposure to carbon monoxide in a hyperbaric oxygen chamber to verify the predicted results of network pharmacology. We found that the mitochondrial ultrastructure of neurons in rats with ACOP was seriously damaged, and apoptotic cells increased significantly. The histopathological changes were obviously alleviated, apoptosis of cortical neurons was inhibited, and the number of Nissl bodies was increased in the SFN group as compared with the ACOP group ( p < .05). Besides, the administration of SFN could increase the expressions of phosphorylated P-AMPK and MFN2 proteins and decrease the levels of DRP1, Caspase3, and Casapase9 proteins in the brain tissue of ACOP rats. These findings suggest that network pharmacology is a useful tool for traditional Chinese medicine (TCM) research, SFN can effectively inhibit apoptosis, protect cortical neurons from the toxicity of carbon monoxide through activating the AMPK pathway and may become a potential therapeutic strategy for brain injury after ACOP.
研究领域:
药理学
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神经科学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Greenhouse Gas Control
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2014
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IF 3.821
Chao Guo,Shaoyun Chen,Yongchun Zhang
Quantitative 13 C nuclear magnetic resonance (NMR) spectroscopy was used to study carbon dioxide (CO 2 ) absorption and desorption, at 313 and 393 K, respectively, from 30 wt% aqueous 2-(2-aminoethylamine)ethanol (AEEA), 30 wt% 2-amino-2-methyl-1-propanol (AMP) and 20 wt% AEEA + 10 wt% AMP solutions. The 13 C NMR results indicate that the main AEEA species are free amine, protonated amine, primary carbamate and secondary carbamate, and the main AMP species are free amine and protonated amine. There is no evident indication that dicarbamate species of AEEA and carbamate of AMP are formed. When AEEA absorbs CO 2 , the formation of AEEA carbamate on primary amine is comparatively faster than that on secondary amine. During the CO 2 desorption process, the AEEA carbamate on secondary amine is produced by an endothermic reaction, which reduces the overall efficiency of desorption. Six cycles of absorption–desorption tests are performed to measure the feasibility of regenerated amine solutions for reuse and the absorption amount of them remains essentially constant during the second to the sixth absorption–desorption experiments. Compared with pure AEEA solution, the recyclability of blended amines, AEEA + AMP, improves while the mol CO 2 /mol amine (CO 2 loading) of the blended amines decreases.
研究领域:
化学工程
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环境化学
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碳捕集与封存（CCS）
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物理化学
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核磁共振（NMR）波谱学
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DOI
高影响因子
危险品化学品经营许可证（带存储）