INORGANIC CHEMISTRY
·
2024
·
IF 4.3
Yong Jian,Gengshen Mo,Weiyuan Xu,Yao Liu,Zhichao Zhang,Yinghui Ding,Ruonan Gao,Jiao Xu,Jiang Zhu,Kun Shu,Zhihan Yan,Fabio Carniato,Carlos Platas-Iglesias,Fangfu Ye,Mauro Botta,Lixiong Dai
In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.
研究领域:
化学
·
材料科学
·
医学成像
·
药理学
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DOI
PubMed
高影响因子
Foods
·
2022
·Vol. 11
·期 21
·3482
·
IF 5.561
Yongmei Li,Lu Li,Jinhong Tian,Fengxin Zheng,Hui Liao,Zean Zhao,Yanyu Chen,Jianxin Pang,Ting Wu
Hyperuricemia (HUA), characterized by abnormal serum uric acid (UA) levels, is recognized as an important risk factor for hyperuricemic nephropathy (HN), which is strongly linked to gut microbiota. This study investigated the protective effects and regulatory mechanisms of insoluble fiber from barley leaves (BL) against HN, induced by adenine (Ad) and potassium oxonate (PO). The results showed that BL dramatically reduced the levels of serum UA and creatinine (CR) and alleviated renal injury and fibrosis. Moreover, BL modulated oxidative stress and downregulated the expression of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in the kidneys of mice with HN. In addition, the 16S rRNA sequence data showed that BL also increased the relative abundance of short-chain fatty acids (SCFAs)-producing bacteria, includingBacteroides,Alloprevotella, andEisenbergiella. Besides, BL treatment also increased SCFAs levels. Of interest, the application of SCFAs in hyperuricemic mice effectively reduced their serum UA. Furthermore, SCFAs dose-dependently inhibited URAT1 and GLUT9 in vitro and potently interacted with URAT1 and GLUT9 in the docking analysis. When taken together, our results indicate that BL and its metabolite SCFAs may be potential candidates for relieving HUA or HN.Keywords:barley leaf;hyperuricemic nephropathy;gut microbiota;SCFAs;URAT1;GLUT9
研究领域:
营养学
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药理学
·
胃肠病学
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肾病学
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DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2024
·Vol. 20
·期 8
·1307-1314
·
IF 2.9
Zhu Yunhan,Chen Renshou
Sepsis-induced Acute kidney injury (SA-AKI), a common complication in sepsis, significantly impacts patients’ health and quality of life. M1 macrophages have been demonstrated to release inflammatory mediators that exacerbate kidney injury. MiR-155 has been implicated in promoting
inflammation and damage during sepsis while reducing miR-155 levels alleviates SA-AKI. However, the relationship between miR-155 and M1 macrophage-derived exosomes in regulating autophagy during SA-AKI remains unclear. In this study, we aim to investigate the relationship between M1 macrophage-derived
exosomes and miR-155 in regulating autophagy during SA-AKI. A mouse model of SA-AKI was established by performing cecal ligation and puncture (CLP) surgery. Additionally, the HK-2 cell line was utilized to establish a sepsis cell model by inducing lipopolysaccharide (LPS). We demonstrated
that the mice model of SA-AKI exhibited renal injury along with enhanced autophagy, inflammation response, and macrophage polarization after CLP surgery. M1 macrophages attenuated cell viability and enhanced autophagy in LPS-treated HK-2 cells. Additionally, M1 macrophage-derived exosomes
were observed to enhance autophagy in LPS-treated HK-2 cells. Furthermore, we confirmed an increased expression of miR-155 in M1 macrophage-derived exosomes. Furthermore, exosome-mediated miR-155 enhanced autophagy in LPS-treated HK-2 cells. In conclusion, this study provides the first evidence
that exosomal miR-155 derived from M1 macrophages enhances autophagy in SA-AKI. These findings suggest that targeting exosomal miR-155 could be a promising therapeutic strategy for SA-AKI.
研究领域:
免疫学
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肾病学
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分子生物学
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重症医学
✓ 已验证
DOI
高影响因子
iScience
·
2024
·
IF 4.6
WenYe Liu,Xi Liu,LingYa Li,ZhiPeng Tai,GuoLiang Li,Jing-Xia Liu
Summary Enhancers of polycomb 1 (EPC1) and 2 (EPC2) are involved in multiple biological processes as components of histone acetyltransferases/deacetylase complexes and transcriptional cofactors, and their dysfunction was associated with developmental defects and diseases. However, it remains unknown how their dysfunction induces hematopoietic stem and progenitor cell (HSPC) defects. Here, we show that depletion of EPC1 / 2 significantly reduced the number of hematopoietic stem and progenitor cells (HSPCs) in the aorta-gonad mesonephros and caudal hematopoietic tissue regions by impairing HSPC proliferation, and consistently downregulated the expression of HSPC genes in K562 cells. This study demonstrates the functions of EPC1 / 2 in regulating histone H3 acetylation, and in regulating DLST (dihydrolipoamide S-succinyltransferase) via H3 acetylation and cooperating with transcription factors serum response factor and FOXR2 together, and in the subsequent HSPC emergence and proliferation. Our results demonstrate the essential roles of EPC1 / 2 in regulating H3 acetylation, and DLST as a linkage between EPC1 and EPC2 with mitochondria metabolism, in HSPC emergence and proliferation.
研究领域:
血液学
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分子生物学
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细胞生物学
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表观遗传学
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DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2017
·Vol. 13
·期 11
·1512-1521
·
IF 4.521
Xu Fujuan,Mu Xiaoyu,Wang Junying,Bian Peixian,Liu Lingfang,Liu Haile,Jing Yaqi,Long Wei,Liu Changlong,Zhang Xiao-Dong
High energy ionizing radiation was widely used in medical diagnosis and cancer radiation therapy. The high dose of X ray or γ ray can cause the damage of cancerous tissue as well as healthy tissue during therapy. Therefore, it is urgent to develop chemical agents to protect
the healthy tissue from high energy ray invasion. Here, the ultrasmall Pt clusters were employed as the anti-radiation agents for protecting healthy cells and improving survival rate of irradiated mice. It was found that Pt clusters can reduce the DNA damages in irradiated cells. In vivo
experiments show that the Pt clusters treatment can improve the survival rate of irradiated mice up to 30%. As a contrast, only-irradiated mice without Pt clusters treatment completely died after 15 days. The detailed biological experiments showed that Pt clusters can recover the bone marrow
DNA level and superoxide dismutase activities via scavenging free radicals. Importantly, the ultrasmall Pt clusters can be excreted rapidly by kidney and do not cause long-term toxicity.
研究领域:
放射治疗
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生物医学工程
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分子生物学
·
毒理学
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DOI
PubMed
高影响因子
ACS Nano
·
2017
·
IF 13.942
Xujiang Yu,Ang Li,Chengzhi Zhao,Kai Yang,Xiaoyuan Chen,Wanwan Li
Multifunctional nanomaterials with integrated diagnostic and therapeutic functions, combination therapy to enhance treatment efficacy, as well as low toxicity have drawn tremendous attentions. Herein, we report a multifunctional theranostic agent based on peptide (LyP-1)-labeled ultrasmall semimetal nanoparticles of bismuth (Bi-LyP-1 NPs). Ultrasmall Bi NPs (3.6 nm) were facilely synthesized using oleylamine as the reducing agent and exhibited a higher tumor accumulation after being conjugated with the tumor-homing peptide LyP-1. The abilities to absorb both ionizing radiation and the second near-infrared (NIR-II) window laser radiation ensured that Bi-LyP-1 NPs are capable of dual-modal computed tomography/photoacoustic imaging and efficient synergistic NIR-II photothermal/radiotherapy of tumors. Moreover, Bi-LyP-1 NPs could be rapidly cleared from mice through both renal and fecal clearance and almost completely cleared after 30 days. Such multifunctional nanoparticles as efficient cancer theranostic agents, coupled with fast clearance and low toxicity, shed light on the future use of semimetal nanoparticles for biomedicine.
研究领域:
生物医学工程
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癌症治疗
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纳米技术
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诊断成像
·
放射治疗
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 6
·e18186
·
IF 4.3
Bo Guan,Ming Li,Di Cui,Chen Shen,Zongyao Hao,Xiaowei Li
Clear cell renal cell carcinoma (ccRCC) represents a significant challenge in oncology, primarily due to its resistance to conventional therapies. Understanding the tumour microenvironment (TME) is crucial for developing new treatment strategies. This study focuses on the role of amyloid precursor protein (APP) in tumour-associated macrophages (TAMs) within the ccRCC TME, exploring its potential as a prognostic biomarker. Basing TAM-related genes, the prognostic model was important to constructed. Employing advanced single-cell transcriptomic analysis, this research dissects the TME of ccRCC at an unprecedented cellular resolution. By isolating and examining the gene expression profiles of individual cells, particularly focusing on TAMs, the study investigates the expression levels of APP and their association with the clinical outcomes of ccRCC patients. The analysis reveals a significant correlation between the expression of APP in TAMs and patient prognosis in ccRCC. Patients with higher APP expression in TAMs showed differing clinical outcomes compared to those with lower expression. This finding suggests that APP could serve as a novel prognostic biomarker for ccRCC, providing insights into the disease progression and potential therapeutic targets. This study underscores the importance of single-cell transcriptomics in understanding the complex dynamics of the TME in ccRCC. The correlation between APP expression in TAMs and patient prognosis highlights APP as a potential prognostic biomarker. However, further research is needed to validate these findings and explore the regulatory mechanisms and therapeutic implications of APP in ccRCC.
研究领域:
肿瘤学
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分子生物学
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转录组学
·
癌症免疫学
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DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 19
·11257-11262
·
IF 3.119
Xitong Huang,Zhiming Xu,Ji-Hua Liu,Bo-Yang Yu,Jiangwei Tian
MicroRNA-21 (miRNA-21) is a significant biomarker which is closely related to some kinds of diseases, such as cancer, cardiovascular disease and kidney disease. Therefore, the detection of miRNA-21 is of great importance and can provide essential information for disease diagnosis. In this study, we report a facile, sensitive assay for miRNA-21 detection using personal glucose meters (PGM). Biotinylated DNA strand linked invertase (Inv) is conjugated on the surface of streptavidin-coated magnetic beads (MBs) to form a MBs–DNA–Inv complex. Target miRNA-21 in the detection system is captured by the MBs–DNA–Inv probe through DNA/RNA hybridization. The duplex-specific nuclease (DSN) enzyme specifically cleaves the DNA to recycle the target miRNA and release invertase, thereby triggering the dual signal amplification and ensuring high sensitivity. Besides, we establish a linear relationship between PGM and different concentrations of miRNA-21 in the range of 10 to 200 pM. The limit of detection is 1.8 pM, which is more sensitive than some of the previous reports. In addition, the biosensor exhibits excellent sequence selectivity and single-base mutation can be discriminated. Moreover, the expression of miRNA-21 is confirmed in urine from mice by our method, which is in good accordance with the qRT-PCR result. Therefore, a dependable, low-cost strategy for the detection of miRNA has been established and it meets the latest analytical demands for miRNA determination that is suitable for the public.
研究领域:
生物传感器
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分子生物学
·
分析化学
·
疾病诊断
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY
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2016
·
IF 3.817
Xu Wang,Yijie Bai,Guyue Cheng,Awais Ihsan,Feng Zhu,Yulian Wang,Yanfei Tao,Dongmei Chen,Menghong Dai,Zhengli Liu,Zonghui Yuan
Quinoxaline 1,4-dioxides (QdNOs) are widely used as a kind of antibacterial growth promoter in animal husbandry. The adrenal cortex was found to be one of the main toxic targets of QdNOs, accompanied by a decreased aldosterone level. However, the way in which QdNOs decrease production of the hormone aldosterone is far from clear. To illustrate the mechanism by which QdNOs damage the adrenal cortex and decrease aldosterone hormone levels, the QdNOs were screened to choose the drug with most toxic effects on aldosterone production, and then to reveal the mechanism between the gene and protein profiles in human adrenocortical cells (NCI-H295R cells). The results found that quinocetone (QCT) showed the highest adrenal toxic effect among QdNOs. After exposing H295R cells to 10 and 20 μM QCT for 24 h, compared with blank cells, the gene and protein expression profiles obtained were analyzed by microarray and MALDI TOF/TOF mass spectrometry, respectively. The results of microarray analysis suggested that ABCG1 and SREBF1, which were involved in the cholesterol biosynthetic and metabolic processes, and CYP17A1, NR4A2 and G6PD, which were related to aldosterone biosynthesis, were important molecular targets. It has been speculated that PKC and ERK pathways might be involved in the reduction of aldosterone production caused by QCT, through enhanced mRNA expression of CYP17A1. Additionally, JNK and p38MAPK signal transduction pathways might participate in apoptosis induced by QCT. Twenty-nine and 32 protein spots were successfully identified when cells were treated with 10 and 20 μM QCT, respectively. These identified proteins mainly included material synthesis and energy metabolism-related proteins, transcription/translation processing-related proteins, signal transduction proteins, cytoskeletal proteins, molecular chaperones, proteins related to response to stress, and transport proteins. Further investigations suggested that oxidative stress caused by QCT was exacerbated through disruption of the Keap1/Nrf2/ARE anti-oxidative stress pathway. Taken together, the data demonstrated for the first time that the Keap1/Nrf2/ARE pathway plays a crucial role in adrenal toxicity, and that CYP17A1 was the key switch to reduce the aldosterone production induced by QCT. Furthermore, large numbers of genes and proteins and entry points for research in the inhibition of aldosterone synthesis induced by QCT were offered, which will provide new insight into the adrenal toxicity of QdNOs and help to provide a theoretical foundation for the formulation of safety controls for products obtained from animals and to design new QdNOs with less harmful effects.
研究领域:
毒理学
·
药理学
·
内分泌学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Yaqi Wang,Ping Shu,Mei Lv,Yonghao Xing,Haoran Zhang,Xiaojing Yan,Bo Wang,Tingting Huang,Minfeng Fang
Farfarae Flos and its honey-processed product are used to treat respiratory diseases; yet their active components and therapeutic targets remained unclear. Herein, we developed an integrated strategy combining receptor chromatography and mice models to screen and evaluate active components in both raw and honey-processed Farfarae Flos. We focused on three key receptors,β 2 -AR, CysLT 1 R, and M 3 R, known to be involved in antitussive, anti-inflammatory, and expectorant activities. These receptors were immobilized onto silica gels to construct affinity columns. Using these columns, we identified the bioactive compounds in both forms of Farfarae Flos. The results revealed an identical set of target-specific compounds across raw and honey-processed samples: chlorogenic acid (CGA) and caffeic acid (CA) targeted β 2 -AR; CGA and rutin bound to CysLT 1 R; and CGA along with isochlorogenic acids A, B, and C interacted with M 3 R. Notably, the interactions of rutin with CysLT 1 R and isochlorogenic acids A, B, and C with M 3 R are reported for the first time. These findings indicate that both raw and honey-fired Farfarae Flos share the same material basis for their antitussive, anti-inflammatory, and expectorant effects, with no significant alteration in pharmacological efficacy due to honey processing. Furthermore, the binding affinities of the bioactive compounds for the receptors correlated well with the molecular docking-predicted binding energies of the corresponding compound-receptor complexes. To our knowledge, this study represents the first target-centric comparative analysis of raw and processed Farfarae Flos. It establishes a generalizable framework for investigating processing-induced changes in herbal pharmacology and provides empirical evidence connecting metabolomic profiles to clinical efficacy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Redox Biology
·
2024
·
IF 10.7
Bi-Xin Xu,Tian-Yu Hu,Jin-Biao Du,Tao Xie,Ya-Wen Xu,Xin Jin,Si-Tao Xu,Hao-Wen Jin,Guangji Wang,Jiankun Wang,Le Zhen
Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production. The prodrug was highly potent in oxidative stress management against cisplatin-induced nephrotoxicity. Strikingly, this prodrug possessed potential feedback activation properties by which the delivered RSSH can further escalate the prodrug activation via NQO1 upregulation. Our strategy pushed RSSH prodrugs one step further in the pursuit of efficient release in biological matrices and improved druggability against oxidative stress.
研究领域:
药学
·
生物化学
·
分子生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2017
·
IF 3.144
Hai Zhang,Shengsheng Zhang,Li Wang,Xiaofei Liu,Yuntang Wu
Previous results from our laboratory showed that chitosan biguanidine hydrochloride (CSGH) and chitooligosaccharide guanidine (COSG) could control glucose uptake by regulating the expression of glucose transporters (GLUTs) in vitro experiments. In this study, we try to delineate changes observed in activation of diacylglycerol (DAG)/protein kinase C- β (PKC- β ) pathway and GLUT2 in kidney. STZ-induced diabetic rats were administered COSG via daily intra-gastric gavage for 8 weeks. Obviously, COSG significantly attenuated fasting blood glucose and blood glucose level by modulating the over-expression of GLUT2 and the level of DAG as well. Immunohistological examination revealed that factors such as PKC- β and transforming growth factor- β (TGF- β ) diminished to various extents after treatment with COSG, which impinged on the synthesis of extracellular matrix (ECM) components like fibronectin (FN). As a result, high glucose-induced activation of DAG/PKC pathway is inhibited, which is associated with the concentration of glucose controlled by the expression of GLUT2 with the treatment of COSG.
研究领域:
药理学
·
糖尿病研究
·
肾病学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）