NMR IN BIOMEDICINE
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2025
·Vol. 38
·期 8
·e70093
·
IF 2.7
Zhongyichen Huang,Qiting Wu,Jing Zhang,Hao Tang,Gang Wu,Yao Zhang,Yi Wang,Dong Liang,Xiaoming Li,Yin Wu
Diabetes mellitus (DM) causes skeletal muscle damage. Energy metabolism alterations in diabetic muscles remain to be elucidated. Chemical exchange saturation transfer (CEST) MRI is increasingly adopted in imaging muscle energy metabolism. This study aimed to investigate energy metabolism alterations in diabetic muscles using CEST MRI. Six adult New Zealand rabbits with alloxan-induced DM were scanned on a 5 T MR imager before and 2, 4, 6, and 8 weeks after the DM model induction, with six normal rabbits as controls. T 2 -weighted imaging, B 1 field mapping, and CEST imaging under four B 1 amplitudes of 0.75, 1.0, 1.25, and 1.5 μT were performed, respectively. Blood glucose level was measured before each MRI experiment. Inverse magnetization transfer ratio analysis was adopted to quantify CEST effects of two energy metabolites of creatine (Cr) and phosphocreatine (PCr), from which their ratio was calculated. B 1 inhomogeneity was corrected using a smoothing spline interpolation algorithm. pH-sensitive CrCEST ratiometric was measured by dividing CrCEST under B 1 of 1.25 μT with that under 0.75 μT. Paired student's t -test and one-way ANOVA were conducted with p < 0.05 considered statistically significant. Blood glucose level measurements confirmed the successfully induced DM model. The controls showed no significant changes in Cr- and PCr-weighted CEST signals throughout the study. In contrast, a significant increase of Cr-weighted CEST signals started in 2 weeks ( p = 0.049) and became more pronounced in Week 6 ( p = 0.045) and Week 8 ( p = 0.002) after the DM model induction, whereas PCr-weighted CEST signals remained constant among multiple time points, leading to significantly reduced PCr/Cr in Week 6 ( p = 0.047) and Week 8 ( p = 0.011). Meanwhile, CrCEST ratio did not show significant alterations ( p > 0.05). The significantly increased Cr-weighted CEST and reduced PCr/Cr with time implied disrupted energy metabolism in diabetic muscles, providing supplementary information for better understanding of DM-related muscle impairments from the metabolic level.
研究领域:
生物医学工程
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内分泌学
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放射医学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Kaixue Zhang,Guoqing Luan,Jin Zhang,Shilong Wang,Min Jiang,Gang Bai
Background Myocardial ischemia (MI) threatens the health of middle-aged and older adults by reducing cardiac oxygen supply and function. Current therapies, including vasodilation, thrombolysis, and interventions, focus on relieving symptoms and improving blood flow but do not adequately address underlying energy metabolism issues. Ligustilide exerts a protective effect on the cardiovascular system and holds the potential for ameliorating MI; however, there is currently no systematic elucidation of ligustilide's target and action mechanism for MI. Purpose This study aimed to comprehensively assess ligustilide's potential targets for improving acute MI and elucidate its underlying mechanism. Methods The therapeutic effects of ligustilide were evaluated at doses of 30, 15, and 7.5 mg/kg over 7 days in a murine model of acute MI induced by isoproterenol hydrochloride. The putative target protein was identified through target fishing, in-gel imaging, and thermal shift assay (TSA), followed by tissue and cell localization studies via a ligustilide probe. The interaction sites between ligustilide and the target protein were elucidated using protein profiling, molecular docking, and TSA at the protein level. Subsequently, knockdown and reconstruction tests were employed at the cellular level to identify the functionally active sites where ligustilide binds to the target protein. Finally, molecular docking and molecular dynamics simulations were conducted to elucidate the underlying mechanism by which ligustilide enhances creatine kinase, M-type (CKMM) protein activity. Results The covalent bonding of ligustilide in cardiac tissue enhances the therapeutic effect on acute MI in mice. For the first time, we found ligustilide specifically targets Cys254 of the CKMM protein following epoxidation. This irreversible binding effectively reduces the proximity between creatine and ATP, promoting creatine phosphorylation and ultimately increasing the creatine phosphate (CP) level by 9.50% to 19.31%. The accumulation of CP alleviates MI by enhancing energy metabolism, mitigating oxidative stress, and suppressing inflammatory responses. Conclusions Our study unveiled ligustilide as a CKMM activator, which effectively enhances the content of CP and mitigates acute MI. The findings significantly contribute to advancing our understanding of ligustilide's function for myocardial protection while proposing a novel activation mechanism of CKMM to improve MI. And the insight into the covalent regulation of the active pocket on CKMM may lead to an alternative therapeutic strategy against acute MI.
研究领域:
药理学
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心血管病学
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DOI
PubMed
高影响因子
Experimental Hematology & Oncology
·
2025
·Vol. 14
·期 1
·1-19
·
IF 13.5
Shan Guangyao,Bian Yunyi,Ren Shencheng,Hu Zhengyang,Pan Binyang,Zeng Dejun,Zheng Zhaolin,Fan Hong,Bi Guoshu,Yao Guangyu,Zhan Cheng
Background Ferroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, is associated with chemoresistance in lung adenocarcinoma (LUAD). This study aims to investigate the role of sarcosine in ferroptosis and its underlying mechanisms.Methods An RSL3-induced ferroptosis model was used to screen a library of 889 human endogenous metabolites and metabolomic profiling was harnessed to identify metabolites associated with ferroptosis. Cell viability, lipid-reactive oxygen species (ROS), ferrous iron, malondialdehyde (MDA), and mitochondrial integrity were assessed to evaluate sarcosine’s effects on ferroptosis. Metabolic fate was studied using 15N-labeled sarcosine. Next, we used untargeted metabolomic profiling and next-generation sequencing to dissect metabolic and transcriptomic changes upon sarcosine supplementation. The effects of sarcosine on ferroptosis and chemotherapy were further validated in patient-derived organoids (PDOs), xenograft models, and LUAD tissues.Results Sarcosine emerged as a potent ferroptosis inducer in the metabolic library screening, which was further confirmed via cell viability, lipid-ROS, ferrous iron, and MDA measurements. Metabolic flux analysis showed limited conversion of sarcosine to other metabolites in LUAD cells, while untargeted metabolomic profiling and seahorse assays indicated a metabolic shift from glycolysis to oxidative phosphorylation. Sarcosine enhanced pyruvate dehydrogenase activity to generate more ROS by interacting with PDK4, reducing PDHA1 phosphorylation. As a co-activator of N-methyl-D-aspartate receptor (NMDAR), sarcosine also exerted its pro-ferroptosis effect via regulating ferrous export through the NMDAR/MXD3/SLC40A1 axis. Given the significance of ferroptosis in chemotherapy, we validated that sarcosine enhanced the sensitization of cisplatin by promoting ferroptosis in LUAD cells, PDOs, and xenograft models.Conclusion Sarcosine promotes ferroptosis and enhances chemosensitivity, suggesting its potential as a therapeutic agent in treating LUAD.
研究领域:
肿瘤学
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代谢组学
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细胞生物学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2023
·
IF 4.8
Weidong Qin,Hongyuan Tian,Zhao Meng,Zhanqiu Tang,Junhua Wang,Zhenglong Wu
We synthesized excitation-dependent fluorescent carbon dots (CDs) through a one-pot hydrothermal process using mango pulps as precursors and discovered that the ozone-treated CDs (O 3 -CDs) could stabilize the diimine form of oxidized 3,3′,5,5′-tetramethylbenzidine (diimine oxTMB). A dual-mode colorimetry and ratiometric fluorescence method using O 3 -CDs and TMB as probes was developed for detecting sarcosine. During measurement, sarcosine was selectively oxidized by sarcosine oxidase, and the resulting hydrogen peroxide was catalyzed by horseradish peroxidase to convert TMB into a blue-colored oxidized product. Under acidic conditions, this product was further oxidized to diimine oxTMB, which exhibited an absorbance band at 450 nm. Due to the inner filter effect, the fluorescence emission of O 3 -CDs at 450 nm was significantly quenched by the diimine oxTMB, while the emission at 550 nm was utilized as a reference signal. The dual-mode method selectively detected sarcosine, with detection limits of 0.034 µM and 0.096 µM for colorimetry and ratiometric fluorescence detection, respectively. The ratiometric fluorescence sensing strategy provided a built-in correction to prevent errors originating from environmental variabilities. Moreover, the stabilization of diimine oxTMB mediated by O 3 -CDs improved the detection performance of the method. This study enriches the library of luminescent CDs through the rational utilization of natural biomass and introduces a novel approach to improve the analytical performance of dual-mode detection.
研究领域:
分析化学
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生物传感
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材料科学
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DOI
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Cheng Hu,Jia-Qi Zhang,Xiao-Yu Zhuang,Zhen-Duo Zhao,Xiao-Jing Qian,Ying Chen
Purpose To study the pharmacological effects of solasonine (Sol) in inhibiting non-small cell lung cancer (NSCLC) metastasis. Methods The pharmacological effects of solasonine were examined in vitro by continuous induction of NSCLC cells by no treatment, or TGF-β, or creatine. Cell migration and invasion were assessed via wound healing and transwell assays, and the levels of epithelial-mesenchymal transition (EMT) markers were determined using immunofluorescence and Western Blot. Solasonineʼs ability to bind to TGF-β and creatine transferases and isoenzymes was assessed by TCGA, KMPLOT database, cellular thermal shift assay (CETSA), and molecular docking assay. In vivo , two types of NSCLC cells were injected into mice using the tail vein. Solasonineʼs effect on tumor metastasis was determined using in vivo fluorescent probes, hematoxylin-eosin staining assay, and immunofluorescence. Results Unlike traditional therapies targeting TGF-β receptors, Sol was shown to inhibit NSCLC metastasis through a novel mechanism independent of TGF-β signaling. Creatine was found to promote NSCLC metastasis in vitro by enhancing cell migration, invasion, and EMT-related protein expression, and in vivo by increasing metastasis to the liver. These effects were mediated by the activation of Smad2 phosphorylation and EMT independently of TGF-β. Sol effectively counteracted these effects by targeting guanidinoacetate methyltransferase (GATM) with high binding affinity, thereby suppressing the TTK-mediated Smad2 pathway and significantly reducing metastasis to the lungs and liver, as confirmed by HE staining and fluorescence imaging. Conclusions This study identifies solasonine as a novel inhibitor of NSCLC metastasis, acting through the GATM and Smad2 pathways to counter creatine-induced metastasis. These findings underscore the potential of Sol as a therapeutic candidate for metastatic NSCLC.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Sinuo Chen,Yifan Ma,Mingyan Ji,Heming Wang,Yun Chen,Dongping Li,Hongyue Jiang,Guangqi Song,Jinglin Xia,Hong Gao
Monocrotaline (MCT), a pyrrolizidine alkaloid (PA), is naturally found in certain plants and known for its hepatotoxic effects. In our prior research, we identified that phosphocreatine (PCr) mitigates PA-induced liver damage. However, the specific mechanism of PCr remains unknown. The objective of the present study was to elucidate the mechanism through which PCr shields against MCT-induced hepatic injury. In vitro assays demonstrated that PCr mitigated the MCT-induced ER stress and apoptosis. This alleviation was similarly observed with the use of the ER stress inhibitor 4-PBA, hinting at the role of ER stress in the protective mechanism of PCr against MCT-induced hepatic damage. In the MCT group, an upregulation of PSRC1 was evident, but this was notably downregulated following PCr treatment in vitro. The silencing of PSRC1 diminished the ER stress and apoptosis triggered by MCT, and the protective effect of PCr on liver injury remained evident. Overexpressing PSRC1 increased MCT-induced apoptosis and ER stress, and PCr still plays a protective role. In vivo experiments, we observed a notable attenuation of MCT-induced liver damage by PCr. Employing RNA sequencing and immunohistochemical staining techniques, we ascertained that endoplasmic reticulum (ER) stress, apoptosis and proline/serine-rich coiled-coil protein 1 (PSRC1) were significantly elevated in the liver samples treated with MCT. Notably, these alterations were counteracted by the presence of PCr. In conclusion, our findings suggest that PCr counteracts ER stress via modulation of PSRC1, which consequently confers protection against MCT-induced liver injury. Furthermore, this study offers potential therapeutic avenues for addressing hepatic damages attributable to MCT
研究领域:
毒理学
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肝脏病学
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分子生物学
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DOI
PubMed
高影响因子
AQUACULTURE NUTRITION
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2025
·Vol. 2025
·期 1
·1151656
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IF 3.9
Nan-Jun Hu,Guang-Li Feng,Xiao-Hong Lai,Mo Peng,Yu-Feng Song
With the increasing prevalence of high-fat diets (HFD) in aquaculture practices, the detrimental effects of HFD on farmed fish have garnered significant attention. Creatine has emerged as a promising green feed additive for aquaculture species; however, its potential role in mitigating the negative impacts of HFD remains poorly understood. To address this knowledge gap, the present study was designed to investigate the protective effects of dietary creatine supplementation on HFD-induced hepatic lipid metabolism disorders and muscle quality deterioration in juvenile grass carp ( Ctenopharyngodon idella ). Three experimental diets were formulated: a control diet (5.20% lipid, control), a HFD (8.11% lipid, HFD), and a HFD supplemented with 2% creatine (HFD + creatine). Juvenile grass carp (initial weight: 4.12 ± 0.02 g) were randomly allocated into nine 300-L indoor tanks and fed the experimental diets for 8 weeks. The key findings of this study revealed that (1) Dietary creatine supplementation significantly ameliorated the adverse effects of HFD on growth performance and feed utilization efficiency in juvenile grass carp. (2) Creatine supplementation improved muscle quality parameters in juvenile grass carp. (3) Dietary creatine attenuated HFD-induced hepatic lipid accumulation through enhanced fatty acid β -oxidation, which was mediated by mfn2-dependent mitochondrial fusion. Notably, this study elucidates a novel molecular mechanism whereby creatine activates mitochondrial fusion through the binding of pparα transcription factor to specific sites on the mitofusin 2 (Mfn2) gene promoter. To our knowledge, this is the first comprehensive investigation from a multi-organ/tissue perspective combined with mitochondrial dynamics analysis, providing valuable insights for developing effective nutritional strategies to counteract HFD-induced adverse effects in farmed fish through creatine supplementation.
研究领域:
水产养殖学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
CONNECTIVE TISSUE RESEARCH
·
2025
·
IF 2.1
Lin Liu,Zhuangzhuang Chu,Xiao Han,Jin Wu,Kunzhan Cai,Jiaohong Wang,Zixiang Guo,Shan Gao,Guoqing Li,Chunbo Tang
Objective We aimed to demonstrate the effects of creatine (Cr) on osteogenic differentiation (OD) in HDPSCs.Materials and methods HDPSCs were treated with Cr and an inhibitor of Cr transporter. The OD capacity was evaluated by detecting ALP staining and activity, alizarin red staining (ARS), as well as osteogenesis-related protein levels. Transcriptomic sequencing, western blotting, transmission electron microscopy, immunofluorescence staining, and autophagy-related protein marker detection were applied to illustrate the underlying mechanism. Furthermore, the impact of Cr on bone regeneration was investigated in vivo.Results We found that 1 mm of Cr effectively enhanced the OD of HDPSCs. The creatine group displayed significantly increased AMPK phosphorylation, overexpressed autophagy-related proteins, enhanced OD, and mineralization capabilities. We also found that ULK1 is the downstream molecule through which AMPK induces cellular autophagy. In vivo results demonstrated that Cr could increase the new bone formation of periodontitis.Conclusion Our research discovered a new AMPK-ULK1-autophagy pathway through which Cr enhances OD in HDPSCs. Cr enhanced HDPSCs-mediated periodontal tissue regeneration in a periodontitis mouse model, providing a theoretical foundation for the study of bone repair in periodontitis.
研究领域:
口腔医学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
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2023
·
IF 6
Bushra Rafique,Rizwan Ullah Khan,Aysha Sarfraz Rizvi,Muhammad Irfan,Ghulam Murtaza,Lili Qiu,Min Xue,Zihui Meng
There is a demand for simple, selective, and efficient assays for the determination of clinically important metabolites such as creatinine for healthcare. Creatinine is the by-product of muscle energy metabolism and is excreted by the kidneys. To measure creatinine in the human serum, a creatinine imprinted photonic crystal hydrogel (CIPC hydrogel) for naked-eye detection is developed. CIPC hydrogel utilizes polystyrene-based two-dimensional (2D) photonic crystal colloidal arrays (PCs-array) embedded in the polyacrylamide hydrogel containing methacrylic acid which imprinted the creatinine template. The nanocavities in the hydrogel produced after the removal of the template bind to and recognize creatinine in the serum samples. The binding is selective and specific for creatinine. The binding is observed as shrinkage of the hydrogel volume and a decrease in the particle spacing which is monitored through changes in the Debye diffraction ring diameter and a visible blue-green to blue color shift. The binding event and the mechanism are investigated by molecular dockings. The CIPC sensor demonstrates a limit of detection (LOD) of 2.45 ± 1.6 µM, a linear detection range (25–500 µM), and recovery from 85.6 % to 99.9 % in the serum samples. CIPC hydrogel is available for the rapid and quantitative onsite detection of creatinine in the human serum sample.
研究领域:
生物医学工程
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分析化学
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产品关联
DOI
高影响因子
ELECTROPHORESIS
·
2022
·Vol. 43
·期 20
·2033-2043
·
IF 3.595
Bin Ran,Chaozhan Chen,Bo Liu,Minbo Lan,Huaying Chen,Yonggang Zhu
The detection of cancer biomarkers is of great significance for the early screening of cancer. Detecting the content of sarcosine in blood or urine has been considered to provide a basis for the diagnosis of prostate cancer. However, it still lacks simple, high-precision and wide-ranging sarcosine detection methods. In this work, a Ti 3 C 2 T X /Pt–Pd nanocomposite with high stability and excellent electrochemical performance has been synthesized by a facile one-step alcohol reduction and then used on a glassy carbon electrode (GCE) with sarcosine oxidase (SO x ) to form a sarcosine biosensor (GCE/Ti 3 C 2 T X /Pt–Pd/SO x ). The prominent electrocatalytic activity and biocompatibility of Ti 3 C 2 T X /Pt–Pd enable the SO x to be highly active and sensitive to sarcosine. Under the optimized conditions, the prepared biosensor has a wide linear detection range to sarcosine from 1 to 1000 µM with a low limit of detection of 0.16 µM (S/N = 3) and a sensitivity of 84.1 µA/mM cm 2 . Besides, the reliable response in serum samples shows its potential in the early diagnosis of prostate cancer. More importantly, the successful construction and application of the amperometric biosensor based on Ti 3 C 2 T X /Pt–Pd will provide a meaningful reference for detecting other cancer biomarkers.
研究领域:
生物医学工程
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肿瘤学
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电化学传感
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DOI
PubMed
高影响因子
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
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2021
·Vol. 22
·期 5
·609-621
·
IF 2.837
Zheng Jing,Changyuan Wang,Shijie Wen,Yue Jin,Qiang Meng,Qi Liu,Jingjing Wu,Huijun Sun,Mozhen Liu
Background: Osteoporosis, characterized by bone loss, usually occurs with the increased bone resorption and decreased bone formation. H2O2-induced MC3T3-E1 cells are commonly used for the study of osteoblastic activities, which play a crucial role in bone formation. Objective: This study aimed to investigate the effects of Phosphocreatine (PCr) on the osteoblastic activities in H2O2-induced MC3T3-E1 cells and elaborate on the possible molecular mechanism. Methods: The Osteoprotegerin (OPG)/Receptor Activator of NF-ΚB Ligand (RANKL) ratio and osteogenic markers were detected to investigate the effects of PCr on osteoblastic activities, and the osteoblastic apoptosis was detected using Hochest staining. Moreover, oxidative stress, Adenosine Triphosphate (ATP) generation and the expression of Sirtuin 1 (SIRT1), Forkhead Box O 1 (FOXO1) and Peroxisome Proliferator-Activated Receptor Γ Coactivator-1α (PGC-1α) were also examined to uncover the possible molecular mechanism in H2O2-induced MC3T3-E1 cells. Result: The results showed that PCr promoted the osteoblastic differentiation by increasing the expression levels of osteogenic markers of Alkaline Phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as increased the OPG/RANKL ratio and suppressed the osteoblastic apoptosis in H2O2-induced MC3T3-E1 cells. Moreover, treatment with PCr suppressed reactive oxygen species (ROS) over-generation and promoted the ATP production as well as increased the PGC-1α, FOXO1 and SIRT1 protein expression levels in H2O2-induced MC3T3-E1 cells. Conclusion: PCr treatment could promote osteoblastic activities via suppressing oxidative stress and increasing the ATP generation in H2O2-induced MC3T3-E1 cells. In addition, the positive effects of PCr on osteoblasts might be regulated by SIRT1/FOXO1/ PGC-1α signaling pathway.
研究领域:
医学
·
分子生物学
✓ 已验证
DOI
高影响因子
Journal of Saudi Chemical Society
·
2020
·
IF 3.517
Pingping Tang,Yaobin Wang,Feiyu He
Accurate determination of Sarcosine (SAR) in urine with high sensitivity and selectivity is important, because it was recently recommended as a prospective biomarker for prostate cancer (PCa) and significant for the early identification of PCa. In this study, an electrochemical sensor based on Fe 3 O 4 incorporated metal–organic frameworks (MOFs) @molecularly imprinted polymer (MIP) was constructed for SAR detection. Magnetic Fe 3 O 4 nanoparticles embedded zeolitic imidazolate framework-8 (ZIF-8) was used as the support of MIP. MIP provides specific recognition sites for template molecules SAR and MOFs increase the rate of mass transfer and adsorption capacity due to the porous structure. The synthesized super-magnetic Fe 3 O 4 @ZIF-8@MIP was self-assembled onto an Au electrode in magnetic field and used as the sensing unit of electrochemical sensor. Cyclic voltammetry was used to monitor the electrochemical behavior, and the binding of SAR resulted in a reduction in the measured current. The results revealed a wide linear range from 1 to 100 pM towards trace SAR determination, with extremely low limit of detection down to 0.4 pM. In conclusion, the Fe 3 O 4 @ZIF-8@MIP based sensor provides a selective, sensitive, and convenient method for SAR diagnosis and other cancer marker detection.
研究领域:
生物医学工程
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分析化学
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癌症诊断
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）