JOURNAL OF CLINICAL LABORATORY ANALYSIS
·
2024
·Vol. 38
·期 10
·e25045
·
IF 2.6
Xiaohua Xu,Yongzhi Xu,Shengqiang Liang
Background The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in various endogenous and exogenous substances on immunoassay for angiotensin I (Ang I), angiotensin II (Ang II), aldosterone, and renin in vitro. Methods Ten endogenous and eight exogenous substances were evaluated at supraphysiologic or supratherapeutic plasma levels using the screening study to identify potential interfering substances. Subsequently, potential interfering substances were further tested within maximum pathological or therapeutic plasma concentration ranges using the dose–response study to determine whether the interference has a significant bias. According to preset acceptance criteria, the interference in potential interfering substances for Ang I, Ang II, and renin and aldosterone assays was determined. Results Six potential interfering substances for Ang I immunoassays were identified, namely valsartan, nifedipine, spironolactone, cholesterol, hemoglobin, and triglyceride. Meanwhile, ethanol, nifedipine, spironolactone, heparin sodium, warfarin, hemoglobin, uric acid, cholesterol, and triglyceride appeared to have potential interference in the Ang II assay. Three identified as possible interferents for aldosterone immunoassays were glucose, valsartan, and spironolactone. Moreover, warfarin, valsartan, spironolactone, uric acid, cholesterol, bilirubin unconjugated, triglyceride, and hemoglobin were potential interfering substances for renin immunoassays. However, only spironolactone of these potential interfering substances exceeded preset mean bias limits (less than ±10.0%) in aldosterone immunoassays. Conclusion Exogenous spironolactone caused clinically significant interference in aldosterone immunoassays. Moreover, the interference in other substances was acceptable in Ang I, Ang II, and renin and aldosterone immunoassays.
研究领域:
医学检验
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RESEARCH ON CHEMICAL INTERMEDIATES
·
2012
·Vol. 39
·期 2
·621-629
·
IF 0.697
Li He-ping,Zhang Juan-juan,Qin Long,Zhao Ming-dong
To develop more potential angiotensin converting enzyme (ACE) inhibitors, a series of captopril (Cap) derivatives were synthesized, including Cap-glycine methyl ester, Cap- l -alanine methyl ester, Cap- l -aspartic acid dimethyl ester, Cap- l -lysine methyl ester, Cap- O -acylisourea, acetyl captopril, and benzoyl captopril. The resulting products were characterized by IR and UV–visible spectroscopy and MS, which showed the desired products were successfully synthesized. This could serve as a guide for rational design of highly potent ACE inhibitors.
研究领域:
药物化学
·
生物化学
✓ 已验证
DOI
高影响因子
Future Science OA
·
2025
·
IF 2.1
Chunyang Wei,Xiaoying Liu,Zhuang Miao,Hua Zhang,Yanfu Wang,Guoxian Qi
Aim The primary objective of this study is to investigate the impact of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), on the process of vascular smooth muscle cell (VSMC) senescence.Methods Rat arterial VSMCs were cultured with angiotensin II to establish a model of premature senescence. The effects of TWEAK and Fn14 on senescent VSMCs were evaluated. Additionally, the role of p38 phosphorylation pathway in the effect of TWEAK on VSMCs senescence was assessed.Results Expressions of TWEAK and Fn14 were significantly elevated in senescent VSMCs. TWEAK activated the p38 phosphorylation pathway and promoted the SA-β-gal staining and P53 expression.Conclusion These preliminary findings suggest that the TWEAK/Fn14 axis may play a crucial role in promoting VSMC senescence.
研究领域:
心血管研究
·
细胞信号传导
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Zetao Heng,Min Hong,Zhaocai Zhang,Ximing Ye,Jianan Zhou,Wentao Wu,Jiabing Rong,Yinchuan Xu
Heart failure with preserved ejection fraction (HFpEF) is a prevalent complex syndrome characterized by diastolic dysfunction with limited therapeutic options. While the renin-angiotensin system (RAS) is implicated in heart failure pathogenesis, the causal contribution of angiotensinogen (AGT), the unique precursor of the RAS, to HFpEF remains undefined. Using a two-hits mouse HFpEF model (high-fat diet + L-NAME), consistent upregulation of hepatic and plasma AGT is identified in wild-type mice of both sexes. Critically, hepatocyte-specific AGT deletion directly ameliorated diastolic dysfunction in male and female HFpEF mice, whereas systemic angiotensin II blockade (losartan) failed to improve cardiac diastolic function. Mechanistically, hepatic AGT drove HFpEF through LRP2-mediated internalization in cardiac endothelial cells, suppressing the GATA2/Pim3 signaling axis, which inhibited microvascular angiogenesis and ultimately exacerbated diastolic dysfunction. To validate therapeutic potential, it is demonstrated that 18β-glycyrrhetinic acid – identified as a potent hepatic AGT inhibitor – significantly improved cardiac diastolic function in HFpEF mice. These findings establish hepatic AGT as a causal contributor to HFpEF pathogenesis and reveal its therapeutic targeting as a promising strategy.
研究领域:
心脏病学
·
分子生物学
·
药理学
·
代谢疾病
·
信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
·
2025
·
IF 4.6
Ying Sun,Dong Wei,Ziming Huang,Jinyao Song,Yiyang Zhang,Yueting Zhou,Bingbing Wang,Can Wang,Jing Wang,Hao Zhang
The inhibitory activity of different ultrafiltration fractions derived from the water-soluble extract of Zhenjiang aromatic vinegar (ZAV) on angiotensin-converting enzyme (ACE) was evaluated, and endogenous peptides with potential ACE inhibition were screened through ultrafiltration and reversed-phase high-performance liquid chromatography (RP–HPLC) coupled with ACE inhibition detection. Several novel ACE inhibitory peptides were identified using a peptidomic approach based on nanoLC-MS/MS. A total of 710 peptides were identified in the RP–HPLC fractions. Additionally, four novel peptides with potential ACE inhibitory activity were identified: FPEQPP, VVPPGHPV, FPPQQP, and YGRGPIE, with IC 50 values of 3.7 ± 0.1 μM, 3.3 ± 0.4 μM, 1.6 ± 0.2 μM, and 5.9 ± 0.2 μM, respectively. Of these novel peptides, FPPQQP was the peptide with the most potent antihypertensive activity, which acted as a strong inhibitor of ACE through molecular docking. These findings suggest that integrating peptidomics and molecular docking provides an efficient strategy for the rapid investigation of ACE inhibitory peptides in food matrices.
研究领域:
食品科学
·
生物化学
·
药理学
✓ 已验证
DOI
高影响因子
Molecular Medicine Reports
·
2018
·Vol. 18
·期 5
·4349-4355
·
IF 1.922
Hangyu Tian,Dan Yu,Yan Hu,Pan Zhang,Yang Yang,Qiang Hu,Ming Li
Angiotensin II (Ang II) is a principal molecule of the renin‑angiotensin system, which promotes hypertrophy and fibrosis. It has been demonstrated that Ang II upregulates the expression of cyclophilin A (CypA), which is a potential myocardial hypertrophy factor. However, the mechanisms by which Ang II induces the expression of CypA in cardiomyocytes remain unclear. In the present study, reactive oxygen species (ROS) were detected by fluorescence microscopy, and western blot analysis and ELISA were used to measure CypA expression. It was identified that Ang II enhanced the production of ROS in rat cardiomyocytes. ROS, in turn, promoted CypA expression and secretion. Notably, the action of Ang II was primarily dependent on the angiotensin type 2 receptor (AT2R), not the type 1 receptor. These results provided an insight into the role of the AT2R signaling pathway in Ang II‑induced myocardial hypertrophy.
研究领域:
心脏病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Long Liu,Zhiwei Qiao,Xinfang Cui,Chunjiao Pang,Hong Liang,Peng Xie,Xuan Luo,Zuqiang Huang,Yanjuan Zhang,Zhongxing Zhao
Introduction of targeted defects into microporous UiO-66s for manipulating their three-dimensional size and surface properties can endow them with adsorption and separation areas involving angiotensin-converting-enzyme-inhibitory (ACE-inhibitory) peptides. Three hydrophobic amino acids (AAs) (i.e., proline (Pro), phenylalanine (Phe), and tryptophan (Trp)) having different physical/chemical properties were applied to in situ tailor defects in UiO-66 through targeted incoordination of missing linkers or missing nodes. Characterization results revealed a uniform oval shape of the developed defects with lengths ranging from 1.8 to 3.1 nm, which was also highly consistent with our molecular simulation. Among these three defective UiO-66s, Phe and Trp imprinted UiO-66s significantly promoted the adsorption affinity of small ACE-inhibitory peptides (uptake: 1.25 mmol g–1 for DDFF and 1.37 mmol g–1 for DDWW) and ultrahigh selectivity for DDFF (249) or DDWW (279) from inactive KKKK solution based on a lock-and-key mechanism. As a result, the imprinted UiO-66 showed an enrichment capacity for ACE-inhibitory peptides about eight times higher than that of pristine UiO-66. Therefore, the amino acid imprinting strategy endorsed by its facile and discerning ability can be envisioned to be of great value for small functional peptide separation and oriented enrichment in biomedicines.
研究领域:
生物化学
·
材料科学
·
药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2017
·
IF 2.466
Fan Chen,Dandan Chen,Yubin Zhang,Liang Jin,Han Zhang,Miyang Wan,Tianshu Pan,Xiaochuan Wang,Yuheng Su,Yitao Xu,Junmei Ye
Interleukin-6 (IL-6) signaling is critical for cardiomyocyte hypertrophy, while the role of IL-6 in the pathogenesis of myocardium hypertrophy remains controversial. To determine the essential role of IL-6 signaling for the cardiac development during AngII-induced hypertension, and to elucidate the mechanisms, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were infused subcutaneously with either vehicle or AngII (1.5 μg/h/mouse) for 1 week. Immunohistological and serum studies revealed that the extents of cardiac fibrosis, inflammation and apoptosis were reduced in IL-6 KO heart during AngII-stimulation, while cardiac hypertrophy was obviously induced. To investigate the underlying mechanisms, by using myocardial tissue and neonatal cardiomyocytes, we observed that IL-6/STAT3 signaling was activated under the stimulation of AngII both in vivo and in vitro . Further investigation suggested that STAT3 activation enhances the inhibitory effect of EndoG on MEF2A and hampers cardiomyocyte hypertrophy. Our study is the first to show the important role of IL-6 in regulating cardiac pathogenesis via inflammation and apoptosis during AngII-induced hypertension. We also provide a novel link between IL-6/STAT3 and EndoG/MEF2A pathway that affects cardiac hypertrophy during AngII stimulation.
研究领域:
心脏病学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BASIC RESEARCH IN CARDIOLOGY
·
2016
·Vol. 112
·期 1
·1-15
·
IF 6.038
Han Jibo,Zou Chunpeng,Mei Liqin,Zhang Yali,Qian Yuanyuan,You Shengban,Pan Yong,Xu Zheng,Bai Bin,Huang Weijian,Liang Guang
Angiotensin II (Ang II) induces cardiac inflammation and remodeling. Emerging evidence indicates that Ang II may utilize the Toll-like receptor 4 (TLR4) signaling pathway in mediating pro-inflammatory and pro-fibrotic activities. However, the precise mechanism is poorly understood. Myeloid differentiation 2 (MD2), a molecule that physically binds to TLR4, confers lipopolysaccharide responsiveness and may also be involved in mediating the actions of Ang II. We hypothesize that MD2 plays an essential role in cardiac inflammation and remodeling induced by local Ang II, and inhibition of MD2 can attenuate Ang II-induced cardiac dysfunction. Using a specific small molecule MD2 blocker L6H21 and the MD2 knockout mice, we show that MD2 deficiency significantly reduces cardiac inflammation and subsequent fibrosis, hypertrophy, and dysfunction in mice challenged with subcutaneous injection of Ang II. In rat cardiomyocyte-like H9c2 cells as well as rat primary cardiomyocytes, inhibition of MD2 by L6H21 or siRNA knockdown suppressed the Ang II-induced TLR4 signaling pathway activation including MyD88 recruitment, and reduced cardiomyocyte hypertrophy and matrix protein expression. These pro-inflammatory activities of Ang II were independent of the AT1 receptor. Finally, we demonstrated the direct interaction between Ang II and MD2 protein via hydrogen bonds on Arg-90, Glu-92, and Asp-100. Ang II produces an inflammatory response and cardiac remodeling by directly binding to MD2, activating MD2/TLR4 complex, and recruiting MyD88. MD2 may be a new therapeutic target for Ang II-mediated cardiac inflammation and remodeling.
研究领域:
心脏病学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Ke Lin,Wu Luo,Na Yang,Lan Su,Hao Zhou,Xiang Hu,Yi Wang,Zia A. Khan,Weijian Huang,Gaojun Wu,Guang Liang
Background Kidney damage is a frequent event in the course of hypertension. Recent researches highlighted a critical role of non-hemodynamic activities of angiotensin II (Ang II) in hypertension-associated kidney fibrosis and inflammation. These activities are mediated through toll-like receptors (TLRs) but the mechanisms by which Ang II links TLRs to downstream inflammatory and fibrogenic responses is not fully known. In this study, we investigated the role of TLR adapter protein called myeloid differentiation primary-response protein-88 (MyD88) as the potential link. Methods C57BL/6 mice were administered Ang II by micro-osmotic pump infusion for 4 weeks to develop nephropathy. Mice were treated with small-molecule MyD88 inhibitor LM8. In vitro , MyD88 was blocked using siRNA or LM8 in Ang II-challenged renal tubular epithelial cells. Results We show that MyD88 is mainly located in tubular epithelial cells and Ang II increases the interaction between TLR4 and MyD88. This interaction activates MAPKs and nuclear factor-κB (NF-κB), leading to increased production of inflammatory and fibrogenic factors. Inhibition of MyD88 by siRNA or selective inhibitor LM8 supresses MyD88-TLR4 interaction, NF-κB activation, and elaboration of inflammatory cytokines and fibrosis-associated factors. These protective actions resulted in decreased renal pathological changes and preserved renal function in LM8-treated hypertensive mice, without affecting hypertension. Conclusion These results demonstrate that Ang II induces inflammation and fibrosis in renal tubular epithelial cells through MyD88 and present MyD88 as a potential point of intervention for hypertension-associated kidney disease.
研究领域:
药理学
·
肾病学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2024
·Vol. 38
·期 8
·e5931
·
IF 1.8
Xu Ji,Liangxi Li,Kaiyue Zhang,Xinyi Yuan,Qian Li,Ge Bai
As a result of the lack of modern techniques, the study of Tibetan medicine has been hindered in identifying bioactive compounds. Herein, we established a chromatographic approach using an immobilized angiotensin II type 1 receptor (AT 1 R) via a one-step method triggered by haloalkane dehalogenase. The bioactive compounds from Choerospondias axillaris (Guangzao) were screened and identified using the immobilized AT 1 R followed by MS. Frontal analysis (FA) and adsorption energy distribution (AED) were used to evaluate the association constants. Molecular docking was used to investigate the binding configurations, and the surface efficiency index, binding efficiency index, and ligand-lipophilicity efficiency (LLE) were calculated to assess the drug-like properties. The results identified naringenin, pinocembrin, and chrysin as the compounds that specifically bind to AT 1 R in Guangzao. FA and AED confirmed that there is only one type of binding site between these compounds and AT 1 R. The association constants were (2.40 ± 0.02) × 10 4 M −1 for naringenin (5.22 ± 0.26) × 10 4 M −1 for pinocembrin, and (4.27 ± 0.14) × 10 4 M −1 for chrysin, respectively. These compounds can bind with AT 1 R through the orthosteric binding pocket. Naringenin exhibited better LLE than pinocembrin and chrysin. These results confirmed the feasibility of using the immobilized AT 1 R column for screening and analyzing bioactive compounds in Tibetan medicines.
研究领域:
药理学
·
中药学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 7
·3117
·
IF 4.6
Zefen Wang,Qian Zhou,Siyuan Liu,Dankui Liao,Pengru Liu,Xiongdiao Lan
Immobilized angiotensin-converting enzyme (ACE) is a promising material for the rapid screening of antihypertensive drugs, but the nonspecific adsorption is a serious problem in separation processes involving complex biological products. In this study, triblock copolymers with dopamine (DA) block as anchors and PEG block as the main body (DA-PEGx-DA) were attached to an immobilized ACE (ACE@mZIF-8/PDA, AmZP) surface via the “grafting to” strategy which endowed them with anti-nonspecific adsorption. The influence of DA-PEGx-DA chain length on nonspecific adsorption was confirmed. The excellent specificity and reusability of the obtained ACE@mZIF-8/PDA/DA-PEG5000-DA (AmZPP5000) was validated by screening two known ACE inhibitory peptides Val-Pro-Pro (VPP, competitive inhibitory peptides of ACE) and Gly-Met-Lys-Cys-Ala-Phe (GF-6, noncompetitive inhibitory peptides of ACE) from a mixture containing active and inactive compounds. These results demonstrate that anchored polymer loops are effective for high-recognition selectivity and AmZPP5000is a promising compound for the efficient separation of ACE inhibitors in biological samples.Keywords:polymer loops;angiotensin converting enzyme;immobilization of enzyme;mesoporous ZIF-8;recognition selectivity
研究领域:
生物化学
·
药物开发
✓ 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）