Gut Microbes
·
2025
·
IF 11
Yingjuan He,Gaomei Zhao,Xue Ouyang,Shaobo Wang,Yin Chen,Chenwenya Li,Yongwu He,Jining Gao,Songling Han,Jinghong Zhao,Junping Wang,Cheng Wang
Ionizing radiation-induced intestinal injury (IRIII) is a catastrophic disease lack of sufficient medical countermeasures currently. Regulation of the gut microbiota through dietary adjustments is a potential strategy to mitigate IRIII. Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention with pleiotropic health benefits. Whether this dietary pattern influences the pathogenesis of IRIII remains vague. We evaluated the impact of TRF on intestinal radiosensitivity in this study and discovered that only daytime TRF (DTRF), not nighttime TRF, could ameliorate intestinal damage in mice that received a high dose of IR. Faecal metagenomic and metabolomic studies revealed that the intestinal creatine level was increased by approximate 9 times by DTRF, to which the Bifidobacterium pseudolongum enrichment contribute. Further investigations showed that creatine could activate the energy sensor AMP-activated protein kinase in irradiated enterocytes and induce phosphorylation of acetyl-CoA carboxylase, resulting in reduced production of polyunsaturated fatty acids and reduced ferroptosis after IR. The administration of creatine mitigated IRIII and reduced bacteremia and proinflammatory responses. Blockade of creatine import compromised the ferroptosis inhibition and mitigation of DTRF on IRIII. Our study demonstrates a radioprotective dietary mode that can reshape the gut microbiota and increase intestinal creatine, which can suppress IR-induced ferroptosis, thereby providing effective countermeasures for IRIII prevention.
研究领域:
放射生物学
·
营养学
·
微生物组研究
·
代谢组学
·
胃肠科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Liyun Zheng,Shiji Fang,Aifang Chen,Weiqian Chen,Enqi Qiao,Minjiang Chen,Gaofeng Shu,Dengke Zhang,Chunli Kong,Qiaoyou Weng,Suqin Xu,Zhongwei Zhao,Jiansong Ji
Sorafenib , a multikinase inhibitor, is the first-line agent for advanced liver cancer. Sorafenib strongly inhibits both cell proliferation and tumour angiogenesis. However, the development of drug resistance hampers its anticancer efficacy. To improve the antitumour activity of sorafenib, we demonstrate that piperlongumine (PL), an alkaloid isolated from the fruits and roots of Piper longum L ., enhances the cytotoxicity of sorafenib in HCCLM3 and SMMC7721 cells using the cell counting kit-8 test. Flow cytometry analysis indicated that PL and sorafenib cotreatment induced robust reactive oxygen species (ROS) generation and mitochondrial dysfunction, thereby increasing the number of apoptotic cells and the ratio of G2/M phase cells in both HCCLM3 and SMMC7721 cells. Furthermore, AMP-protein kinase (AMPK) signalling was activated by excess ROS accumulation and mediated growth inhibition in response to PL and sorafenib cotreatment. RNA-sequencing analysis indicated that PL treatment disrupted RNA processing in HCCLM3 cells. In particular, PL treatment decreased the expression of cleavage and polyadenylation specificity factor 7 (CPSF7), a subunit of cleavage factor I , in a time- and concentration-dependent manner in HCCLM3 and SMMC7721 cells. CPSF7 knockdown using a gene interference strategy promoted growth inhibition of PL or sorafenib monotherapy , whereas CPSF7 overexpression alleviated the cytotoxicity of sorafenib in cultured liver cancer cells. Finally, PL and sorafenib coadministration significantly reduced the weight and volume of HCCLM3 cell xenografts in vivo. Taken together, our data indicate that PL displays potential synergistic antitumour activity in combination with sorafenib in liver cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL PHYSIOLOGY
·
2021
·Vol. 106
·期 3
·653-662
·
IF 2.969
Xiujin Shi,Yi Zhang,Baidi Lin,Yang Zhou,Wei Suo,Juanjuan Wei,Lin Zhang,Jie Lin,Fucheng Xiao,Limin Zhao,Yang Lin
New Findings What is the central question of this study? Does danthron alleviate experimental atherosclerosis by inhibiting the formation of foam cells? What are the main findings and their importance? Danthron improved serum lipid profiles and significantly reduced the atherosclerotic plaque areas and lipid accumulation in the aortic root of ApoE −/− mice. Danthron inhibited foam cell formation in oxidized low-density lipoprotein-induced RAW264.7 macrophages. Furthermore, danthron exerted its function in atherosclerosis at least partly through activating the AMP-activated protein kinase–sirtuin 1 signalling pathway. These findings suggest that danthron has the potential to alleviate atherosclerosis. Danthron, an ingredient isolated from Rheum palmatum L., has been revealed to reduce lipid accumulation in vitro . This study aimed to discover the effects of danthron on the development of atherosclerosis and to delineate the underlying mechanisms. For in vivo studies, male ApoE −/− mice were fed a high-fat diet and orally treated with danthron (30 or 60 mg/kg/day) for 12 weeks. For in vitro studies, RAW264.7 cells were induced by oxidized low-density lipoprotein (ox-LDL, 50 μg/ml) for 48 h and subsequently administered danthron at appropriate concentrations for 24 h. AMP-activated protein kinase (AMPK) inhibitor compound C was added to ox-LDL-stimulated RAW264.7 cells 2 h before danthron administration to confirm the role of the AMPK signalling pathway in the regulation by danthron of foam cell formation. We found that danthron improved serum lipid profiles, and significantly reduced atherosclerotic plaque areas and lipid accumulation in the aortic root of atherosclerotic mice. Moreover, danthron upregulated the mRNA and protein expression of ATP-binding cassette transporter A1 (ABCA1), ABCG1 and liver X receptor α (LXRα), which play a crucial role in lipid metabolism, and activated the AMPK–sirtuin 1 (SIRT1) pathway. In an in vitro study, danthron inhibited foam cell formation in ox-LDL-induced RAW264.7 macrophages with an increase in the expression of ABCA1, ABCG1 and LXRα as well as activation of the AMPK–SIRT1 pathway. Furthermore, compound C abolished the effects of danthron on lipid accumulation and the protein expression of ABCA1/G1 and LXRα in vitro . Our results highlight that danthron possesses potential benefits in alleviating experimental atherosclerosis by targeting foam cell formation by activating the AMPK–SIRT1 signalling pathway.
研究领域:
心血管疾病
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENERGY & FUELS
·
2025
·
IF 5.3
Yinchun Liang,Hongyu Duan,Weida Chen,Lihui Sun,Feng Zhang
New absorbents combining the advantages of phase separation and easily regenerated products were prepared with 2-methyl-2-amino-1-propanol (AMP) as the main absorbent and tertiary amines as the auxiliary absorbents and phase splitters. The absorption performances of absorbents containing different tertiary amines were systematically compared. Among these tertiary amines, N,N,N′,N′-tetramethyl-1,3-propanediamine (TMPDA) exhibited the most effective properties. For the absorbent TMPDA–AMP–H2O system (TAH), an absorption load of approximately 2.6 mol/kg was achieved. The kinetic and thermodynamic properties of TAH absorption were evaluated. It was found that the absorption products were readily decomposed into HCO3–, and the regeneration efficiency of TAH was above 91% at 358 K, while the regeneration energy consumption was only 2.0 GJ/t CO2. It should be noted that the addition of TMPDA effectively inhibited the precipitation of bicarbonate, thus leading to a higher absorption capacity and lower energy consumption per ton of CO2 loaded.
研究领域:
化学工程
·
环境科学
·
材料科学
·
能源技术
✓ 已验证
产品关联
DOI
高影响因子
NATURE CELL BIOLOGY
·
2024
·
IF 17.3
Son Sung Min,Park So Jung,Breusegem Sophia Y.,Larrieu Delphine,Rubinsztein David C.
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth, metabolism and autophagy. Multiple pathways modulate mTORC1 in response to nutrients. Here we describe that nucleus–cytoplasmic shuttling of p300/EP300 regulates mTORC1 activity in response to amino acid or glucose levels. Depletion of these nutrients causes cytoplasm-to-nucleus relocalization of p300 that decreases acetylation of the mTORC1 component raptor, thereby reducing mTORC1 activity and activating autophagy. This is mediated by AMP-activated protein kinase-dependent phosphorylation of p300 at serine 89. Nutrient addition to starved cells results in protein phosphatase 2A-dependent dephosphorylation of nuclear p300, enabling its CRM1-dependent export to the cytoplasm to mediate mTORC1 reactivation. p300 shuttling regulates mTORC1 in most cell types and occurs in response to altered nutrients in diverse mouse tissues. Interestingly, p300 cytoplasm–nucleus shuttling is altered in cells from patients with Hutchinson–Gilford progeria syndrome. p300 mislocalization by the disease-causing protein, progerin, activates mTORC1 and inhibits autophagy, phenotypes that are normalized by modulating p300 shuttling. These results reveal how nutrients regulate mTORC1, a cytoplasmic complex, by shuttling its positive regulator p300 in and out of the nucleus, and how this pathway is misregulated in Hutchinson–Gilford progeria syndrome, causing mTORC1 hyperactivation and defective autophagy.
研究领域:
细胞生物学
·
分子生物学
·
医学遗传学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 6
·1-10
·
IF 6.232
You Xinrui,Huang Chunyu,Luo Yuxin,Shi Guoyue,Zhou Tianshu,Deng Jingjing
A smartphone-based detection platform for the determination of alkaline phosphatase (ALP) is described. The method is based on the rational design of the stimulus–response of 7-methoxycoumarin-3-carboxylic acid (7-MC-3-COOH)–functionalized Eu-AMP infinite coordination polymer (ICP) nanoparticles. The blue fluorescence of 7-MC-3-COOH at 403 nm was suppressed, while the red fluorescence of Eu 3+ at 615 nm was sensitized after the formation of 7-MC-3-COOH@Eu-AMP ICP. Upon exposure to ALP, the dephosphorylation of AMP resulted in the destruction of 7-MC-3-COOH@Eu-AMP ICP, and thereby, the blue fluorescence of 7-MC-3-COOH recovered; in the meantime, the sensitized red fluorescence was quenched. With the fluorescence intensity ratio F 615 / F 430 as the signal readout, ALP can be detected within a concentration range 0.001 to 0.15 U mL −1 , and the limit of detection (LOD) was 0.00035 U mL −1 . Moreover, fluorescence color changes from red to blue could also be recognized by a portable device with the smartphone as a signal reader, and direct point-of-use testing (POUT) for ALP within a concentration range 0.005 to 0.7 U mL −1 could be realized, with LOD of 0.0015 U mL −1 . Endowed with high sensitivity and superior reliability, the assay enabled direct monitoring of P-related water eutrophication in a freshwater lake with ALP as an indicator.
A smartphone-based platform for point-of-use determination of alkaline phosphatase.
研究领域:
环境科学
·
分析化学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·Vol. 33
·期 18
·2214059
·
IF 19
Xinyue Li,Yuanyuan Fan,Zhengbao Zha,Deyan Gong,Jiajia Yu,Qianhui Li,Ruoyao Li,Hua Wang,Fei Wang
Cordycepin (3′-deoxyadenosine) has a demonstrated value in ameliorating nonalcoholic steatohepatitis (NASH); however, its short in vivo metabolism time and high dose-induced cytotoxicity are challenges limiting its clinical application. Herein, a cordycepin-loaded macrophage vesicle (C-MV) is developed for targeted cordycepin delivery to achieve stable and durable mitigation of NASH. The C-MV is obtained using cytochalasin B-stimulated RAW 264.7 cells to produce MV, followed by repeated freeze-thawing and extrusion of MV and cordycepin. C-MV selectively delivers cordycepin to macrophages at the site of liver injury, slowly releases cordycepin, reduces the toxicity associated with high cordycepin doses, and increases the mice's survival rate from 40% to 90%. Moreover, C-MV reduces liver apoptosis and attenuated NASH liver injury by activating AMP-activated protein kinase and inhibiting caspase 6 activity. Overall, C-MV exhibits better anti-inflammatory, lipid-lowering, and anti-apoptosis properties than free cordycepin, making it a promising delivery system for the potential clinical application of cordycepin. MV combined with cordycepin provides an inspiring bionic strategy for NASH treatment that can achieve effective therapeutic effects in vivo.
研究领域:
药理学
·
肝病学
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Zhongshuai Zhao,Ran Li,Ying Zhu,Zhongde Liu
Hydrogen sulfide (H 2 S), playing unique role on signal transmission in various physiological processes, the rapid and accurate monitoring of it is particularly concerned. The drawbacks of fluorescence probe for H 2 S, namely poor selectivity or long response time, have always existed. As a test case, here headspace separation combined fluorescence strategy was attempted, on basis of H 2 S stimuli-responsive AMP/Tb 3+ /Ag + or GMP/Tb 3+ /Ag + coordination polymer probes. The fluorescence intensity of them is inversely proportional to the concentration of it, due to Ag-S in situ coordination and partial formation of Ag 2 S. Using the hybrid analysis, a quick response of less than 2.0 min and a high selectivity could be obtained. The signal change (Δ I ) of AMP/Tb 3+ /Ag + or GMP/Tb 3+ /Ag + showed good linearity within the range of 0.5–100 μM and 1.0–150 μM, along with a detection limit (3 σ ) of 0.2 and 0.4 μM, respectively. When utilized to determine the sulfide level in real samples, it shows recoveries from 96.4 % to 102.3 % with relative standard derivation ( RSD ) less than 3.0 %. The combination strategy of headspace separation and fluorescence quantitative analysis was verified to effectively eliminate potential interference such as other coexisting non-volatile thiol-containing species, providing a novel avenue to flexibly design the volatile component analysis with high selectivity in complex sample matrixes.
研究领域:
分析化学
·
环境科学
·
生物化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Dong Yang,Zeyu Shou,Xiaoling Xie,Yi Tang,Zhiyun Li,Hao Chen,Sicheng Tang,Xingjie Zan
Diabetic wound therapy presents significant challenges in the clinical environment, where persistent bleeding, disturbed inflammatory regulation, impaired cellular proliferation, and impaired tissue remodeling are major features of diabetic wound healing. However, current treatment strategies need to be considered in the context of the dynamic and complex needs of chronic wound healing. Here, multifunctional dynamic boronic acid cross-linked hydrogels were prepared by the reaction of gelatin (Gel) inoculated with 5-carboxy 3-nitrophenylboronic acid (NPBA) and Epigallocatechin gallate (EGCG) to achieve rapid gelation at pH = 7.4, EGCG could interact electrostatically with cationic antimicrobial peptides (AMP) to achieve the effective loading of AMP in the hydrogels. This hydrogel can be injected and adhered to skin defects in diabetic patients to provide a barrier and rapid hemostasis. In a high glucose microenvironment, the rapid release of AMP effectively kills bacteria, while the responsive release of EGCG eliminates reactive oxygen species (ROS) and promotes macrophage M2 polarization. In addition, the hydrogel had excellent biocompatibility and degradability properties, degraded completely after 3 days of subcutaneous injection, and was non-toxic in H&E staining of major organs and serum liver function indices in mice. This multifunctional injectable hydrogel accelerates diabetic skin wound repair and is a promising dressing for the precise treatment of diabetic wounds.
研究领域:
材料科学
·
生物医学工程
·
伤口愈合
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2018
·
IF 4.439
Wei Huang,Junzhe Xu,Dingkun Lu,Jingjing Deng,Guoyue Shi,Tianshu Zhou
In this study, novel magnetic infinite coordination polymer Fe 3 O 4 @Tb/AMP core-shell nanoparticles were rationally designed and fabricated as recyclable adsorbents for selective removal of anionic dyes from colored wastewater. The core-shell nanoparticles used in this study are composed of two components: the shell is the supramolecular infinite coordination polymers (ICPs) network formed by terbium ions (Tb 3+ ) and adenosine 5 ′ -monophosphate monohydrate (AMP) ligands and the core is the Fe 3 O 4 nanoparticles which are encapsulated into the ICP network by the self-adaptive inclusion process. The prepared core-shell nanoparticles showed superiority in strong magnetism and selective adsorption towards anionic dyes, such as Alizarin Red (AR) and Congo Red (CR). Parameters that influenced the adsorption process, such as solution pH, salt concentration and adsorbent dosage were investigated. Under the optimal conditions, adsorption kinetics, isotherms and thermodynamics were also determined. Notably, this nano-adsorbent exhibited rapid adsorption feature (almost 96% dye removal in 5 min) and the adsorption isotherm data fitted quite well with the Langmuir model with an estimated maximum adsorption capacity of 357.14 mg g −1 for AR and 909.09 mg g −1 for CR at 298 K. This capacity could be further enhanced at the higher temperatures. In addition, the Fe 3 O 4 @Tb/AMP core-shell nanoparticles could be regenerated by a simple salt/ethanol-washing method and used with high recyclability over five cycles. With the magnetically separable Fe 3 O 4 @Tb/AMP core-shell nanoparticles as adsorbents, selective removal of toxic anionic dyes from colored wastewater could be realized directly, which is of great importance for the sustainable development of dye contaminated wastewater treatment technology.
研究领域:
环境科学
·
材料科学
·
化学工程
·
纳米技术
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2015
·
IF 4.383
Zhenzhen Liu,Haijun Gong,Rui Zeng,Xuan Liang,Li-Ming Zhang,Liqun Yang,Yuqing Lan
A hyperbranched cationic polysaccharide derivative-mediated small interfering (si)RNA interference strategy was proposed to inhibit nuclear transcription factor-kappa B (NF-κB) activation in human retinal pigment epithelial (hRPE) cells for the gene therapy of diabetic retinopathy. Two hyperbranched cationic polysaccharide derivatives containing the same amount of cationic residues, but with different branching structures and molecular weights, including 3-(dimethylamino)-1-propylamine-conjugated glycogen (DMAPA-Glyp) and amylopectin (DMAPA-Amp) derivatives, were developed for the efficient delivery of NF-κB siRNA into hRPE cells. The DMAPA-Glyp derivative showed lower toxicity against hRPE cells. Furthermore, the DMAPA-Glyp derivative more readily condensed siRNA and then formed the nanoparticles attributed to its higher branching architecture when compared to the DMAPA-Amp derivative. Both DMAPA-Glyp/siRNA and DMAPA-Amp/siRNA nanoparticles were able to protect siRNA from degradation by nuclease in 25% fetal bovine serum. The particle sizes of the DMAPA-Glyp/siRNA nanoparticles (70–120 nm) were smaller than those of the DMAPA-Amp/siRNA nanoparticles (130–180 nm) due to the higher branching architecture and lower molecular weight of the DMAPA-Glyp derivative. In addition, the zeta potentials of the DMAPA-Glyp/siRNA nanoparticles were higher than those of the DMAPA-Glyp/siRNA nanoparticles. As a result, siRNA was much more efficiently transferred into hRPE cells using the DMAPA-Glyp/siRNA nanoparticles rather than the DMAPA-Amp/siRNA nanoparticles. This led to significantly high levels of suppression on the expression levels of NF-κB p65 messenger RNA and protein in the cells transfected with DMAPA-Glyp/siRNA nanoparticles. This work provides a potential approach to promote hyperbranched polysaccharide derivatives as nonviral siRNA vectors for the inhibition of NF-κB activation in hRPE cells.
研究领域:
药理学
·
分子生物学
·
眼科学
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
REPRODUCTION FERTILITY AND DEVELOPMENT
·
2021
·Vol. 33
·期 12
·700-712
·
IF 2.311
Xin Zhan,Yiran Xie,Liping Sun,Qi Si,Hongkai Shang,Xin Zhan,Yiran Xie,Liping Sun,Qi Si,Hongkai Shang
This study explored the molecular mechanism underlying the effects of dexamethasone (DEX, 1 µM) on glucose transporters (GLUT) in JEG-3 human placental choriocarcinoma cells. JEG-3 cells were treated with DEX, an expression plasmid encoding human glucocorticoid receptor α (GRα), pcDNA3.1-GRα, GRα short interference (si) RNA, LY294002, xanthine oxidase (XO)/hypoxanthine (HX), rapamycin, insulin-like growth factor (IGF) 1, N-acetylcysteine (NAC) or phosphatidic acid (PA), and cell proliferation, apoptosis, mitochondrial membrane potential (MMP), human chorionic gonadotrophin (hCG) content, human placental lactogen (hPL) content, glucose uptake, reactive oxygen species levels and signalling pathway modulation were evaluated. Treatment of JEG-3 cells with DEX (1 µM), GRα siRNA, LY294002 (50 µM), XO/HX (7.2 µM/36 nM) or rapamycin (80 nM) inhibited cell proliferation, induced apoptosis, significantly decreased MMP and hCG and hPL content and increased ROS levels. In addition, glucose uptake was decreased through downregulation of the mRNA and protein expression of GRα, GLUT1 and GLUT3. Treatment of JEG-3 cells with GRα siRNA, LY294002, XO/HX or rapamycin inhibited phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3 and mammalian target of rapamycin (mTOR) and induced the phosphorylation of AMP-activated protein kinase (AMPK) and tuberous sclerosis complex 2. The effects of GRα overexpression and IGF1 (100 nM), NAC (5 nM) or PA (100 µM) treatment on JEG-3 cells contrasted with those of DEX treatment. DEX blocked glucose uptake by downregulating GRα expression, which reduced GLUT1 and GLUT3 mRNA and protein expression, which, in turn, may have inhibited the PI3K/AKT/mTOR pathway and activated the ROS/AMPK pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）