JOURNAL OF CLINICAL LABORATORY ANALYSIS
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2024
·Vol. 38
·期 10
·e25045
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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
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内分泌学
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DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 4
·e70208
·
IF 3.4
Wenpu Yao,Junyi Li,Xiaoyan Zhu,Ruiyang Ma,Yunpeng Xu,Ruida Ma,Zihao Guo,Guangqing Mu,Xuemei Zhu
Hypertension is a common chronic disease driven by multiple physiological mechanisms, primarily the overactivation of the renin–angiotensin system (RAS). Gamma-aminobutyric acid (GABA), a nonprotein amino acid, has well-documented health benefits, including antihypertensive and calming effects. This study evaluates the blood pressure-lowering effects of Lactiplantibacillus plantarum DPUL-F233 bacterial powder in spontaneously hypertensive rats (SHRs). The bacterial powder was produced using optimized fermentation and freeze-drying techniques. In the oral administration experiment on SHRs, the group treated with a high dose of bacterial powder via long-term gavage showed a significant reduction in blood pressure compared to the untreated group. Specifically, the final measurements of diastolic and systolic blood pressure were reduced to 206.0 ± 2.35 mm Hg and 145.0 ± 6.78 mm Hg, respectively. The angiotensin-converting enzyme I/Angiotensin II/AT1R axis was downregulated, while the angiotensin-converting enzyme II/Angiotensin 1–7/MasR axis was upregulated, rebalancing the RAS signaling pathway. The high-dose group also demonstrated protective effects on the heart and kidneys, with significant improvements observed in reducing cardiac hypertrophy and kidney damage. Additionally, molecular simulation studies indicated potential inhibition of ACE I by GABA. The results suggest that GABA-rich L. plantarum DPUL-F233 powder has significant potential as a natural antihypertensive supplement, particularly for use in functional food development.
研究领域:
微生物学
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医学
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营养学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2017
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IF 8.402
Yujie Su,Yahui Hu,Yu Wang,Xiangting Xu,Yang Yuan,Yunman Li,Zeyuan Wang,Kerong Chen,Fangrong Zhang,Xuefang Ding,Min Li,Jianping Zhou,Yuan Liu,Wei Wang
Multi-walled carbon nanotube (MWNT) with its versatility has exhibited tremendous superiority in drug delivery. Despite plenty of researches on MWNT based delivery systems, precision-guided assistances to maximize their profitable properties are still lacking in substantive progress. We developed here a dual-targeting and co-delivery system based on MWNT for antiangiogenesis therapy in lung cancer which aimed at renin-angiotensin system (RAS) dysregulation by synergistically conducting angiotensin II type 1 receptor (AT 1 R) and type 2 receptor (AT 2 R) pathway. In this work, iRGD peptide connected to polyethyleneimine (PEI) was linked to MWNT skeleton, accompanying with candesartan (CD) conjugated to MWNT mediated by cystamine (SS). The functionalized MWNT is assembled with plasmid AT 2 (pAT 2 ) to form iRGD-PEI-MWNT-SS-CD/pAT 2 complexes. iRGD and CD act as pilots for complexes to dually target symbolic ανβ3-integrin and AT 1 R both overexpressed on tumor angiogenic endothelium and lung cancer cell. CD as chemotherapy showed synergistic downregulation of VEGF when combining of pAT 2 and efficiently inhibited angiogenesis . iRGD-PEI-MWNT-SS-CD/pAT 2 complexes greatly appreciated drug activities by changing drug distribution and exhibited remarkable tumor growth suppression in A549 xenograft nude mice . Our work presents that such dual-targeting strategy highly improves the delivery performance of MWNT and open a new avenue for RAS related lung cancer therapy.
研究领域:
肿瘤学
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纳米医学
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药理学
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DOI
PubMed
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2024
·Vol. 38
·期 6
·e9703
·
IF 1.8
Xi Gao,Xiaoyong Li,Lingyun Chen,Shuyan Chen,Guixue Hou,Liang Lin,Qunjie Wang,Jiuxin Qu,Siqi Liu
Rationale Secondary hypertension is often caused by activation of complex multi-organ endocrine systems, while renin activity indicated by angiotensins (Angs), aldosterone (ALD) and cortisol (COR) in such systems are generally accepted as its diagnostic markers. As antibody-based methods cannot offer comparable quantification for these biomarkers, a liquid chromatography (LC)–tandem mass spectrometry (MS/MS)-based approach was developed to quantify them simultaneously and accurately. Methods Five different beads for magnetic solid-phase extraction (MSPE) were evaluated towards their enrichment efficiency for these biomarkers. An LC system with optimized elution gradient and a triple-quadrupole MS with tuned parameters were coupled to quantitatively monitor the extracted analytes. The method performance was further examined such as linearity, precision, stability, recovery rate and matrix effect. Based on the developed method, the abundance of Ang II, ALD and COR in plasma was measured and the quantification was compared with that derived from commercial ELISA kits. Results As compared with other MSPEs, Angs, ALD and COR were highly enriched by the HLB magnetic beads with satisfactory recoveries. These analytes were simultaneously quantified by LC/MS/MS and all the method parameters for quantification were well matched with the requirements of clinical testing. Comparison of the quantitative results derived from ELISA and LC/MS/MS exhibited that the two methods offered basically comparable values with Pearson r values at 0.896, 0.895 and 0.835, respectively. The stability test for plasma Angs at room temperature indicated that the abundance of Ang II was relatively stable within 3 h, whereas that of Ang I and Ang 1–7 was time-dependently changed. Conclusions Coupling of HLB beads and LC/MS/MS thus enables simultaneous quantification of a set of biomarkers related to secondary hypertension.
研究领域:
医学
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分析化学
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2025
·
IF 4.2
Fei Qian,Zhengyu Zhu,Chao Luo,Ruofan Qi,Lun Wei,Le Bo,Wangtao Jiang,Caiping Mao
Chronic stress could impair ovarian reserve through hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to reduced oocyte quality and endocrine dysfunction. The ovarian renin-angiotensin system (OVRAS) modulates follicular development, and excessive activation of the ACE-AngII-AT1R axis increases oxidative stress, disrupting ovarian function. This study investigates OVRAS's role in chronic unpredictable stress (CUS)-induced diminished ovarian reserve (DOR) and explores the protective effects of chlorogenic acid (CGA). Female mice were subjected to CUS (10 intervention methods were randomly applied to mice according to low, medium, and high frequency) and CGA treatment. Hormone levels, estrous cycles, ovarian morphology, oxidative stress, and apoptosis were evaluated. Results demonstrated that CUS overactivated the ACE-AngII-AT1R axis, increasing oxidative stress and apoptosis in granulosa cells (GCs). CGA improved ovarian function, reduced oxidative stress, and downregulated ACE-AngII-AT1R axis activity. CGA may alleviate stress-induced DOR by mitigating oxidative stress and apoptosis via modulation of the ACE-AngII-AT1R axis.
研究领域:
生殖生物学
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内分泌学
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药理学
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
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2025
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IF 2.5
Peiying Shi,Shuo Han,Yang Sun,Mengmeng Li,Xueling Xu
Pathological cardiac hypertrophy (CH) often progresses towards heart failure, which presents a serious threat to global public health security. Fortunately, peptides from animal venoms have emerged as potential drugs for the therapeutic care of cardiovascular diseases. This paper aims to investigate the therapeutic potentials and mechanism of bee venom (BV) using isoproterenol (ISO)-induced CH models in vivo and in vitro . Melittin was identified as the dominant component in air-dried BV using UPLC-Q/TOF-MS, and subsequently it confirmed that BV prevented electrocardiogram and echocardiography abnormalities, and attenuated morphological and histopathological alterations of hypertrophic hearts in mice. Mechanistically, through network pharmacology exploration, angiotensin-converting enzyme (ACE) and renin (REN) were predicted as the key targets of melittin against CH. This was further confirmed by the in vitro experimental results that BV significantly downregulated the protein or mRNA expression levels of CH markers (β-MHC, ANP, BNP), ACE, and IL-1β in ISO-induced hypertrophic cardiomyocytes. Furthermore, it was ascertained that BV inhibited JAK2/NF-κB signaling cascade via decreasing the protein expression ratio of p-JAK2/JAK2 and the protein expression level of NF-κB. This study showed that BV alleviated ISO-induced CH in vivo and in vitro via JAK2/NF-κB signaling cascade, providing a basis for treating CH with BV or melittin.
研究领域:
药理学
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心血管医学
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分子生物学
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毒理学
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生物医学研究
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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
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分子生物学
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药理学
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代谢疾病
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信号转导
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
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IF 15.8
Chengming Qu,Haitao Yuan,Ming Tian,Xiaodong Zhang,Peng Xia,Guangwei Shi,Rui Hou,Ji Li,Haibo Jiang,Zhiyong Yang,Tengxiang Chen,Zhijie Li,Jigang Wang,Yufeng Yuan
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its resistance against chemotherapy and immunotherapy due to its dense desmoplastic and immunosuppressive tumor microenvironment (TME). Traditional photodynamic therapy (PDT) was also less effective for PDAC owing to poor selectivity, insufficient penetration, and accumulation of photosensitizers in tumor sites. Here, we designed a light-responsive novel nanoplatform targeting the TME of PDAC through tumor-specific midkine nanobodies (Nbs), which could efficiently deliver semiconducting polymeric nanoparticles (NPs) to the TME of PDAC and locally produce abundant reactive oxygen species (ROS) for precise photoimmunotherapy. The synthesized nanocomposite can not only achieve multimodal imaging of PDAC tumors (fluorescence and photoacoustic imaging) but also lead to apoptosis and immunogenic cell death of tumor cells via ROS under light excitation, ultimately preventing tumor progression and remodeling the immunosuppressive TME with increased infiltration of T lymphocytes. Combined with a PD-1 checkpoint blockade, the targeted PDT platform showed the best antitumor performance and markedly extended mice survival. Conclusively, this work integrating Nbs with photodynamic NPs provides a novel strategy to target formidable PDAC to achieve tumor suppression and activate antitumor immunity, creating possibilities for boosting efficacy of immunotherapy for PDAC tumors through the combination with precise local PDT.
研究领域:
肿瘤学
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生物医学工程
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纳米技术
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免疫学
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癌症治疗
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2025
·
IF 8
Chuan Liang,Yang Chen,Yunzhe Ling,Peirun Li,Jiahao Liu,Xuantian Li,Yanhua Xu,Zhiying Liu
Non-steroidal anti-inflammatory drugs (NSAIDs), though designed to target specific molecular pathways, pose significant environmental risks to non-target organisms, particularly marine fish. This study investigated the toxicity mechanisms and adaptive responses to diclofenac (DCF) and meloxicam (MEX) during the early life stages (ELS) of Oryzias melastigma at environmentally relevant concentrations over a 31-day period. Mechanistic investigations of sub-lethal effects were conducted using Enzyme-Linked Immunosorbent Assay (ELISA), RNA sequencing (RNA-Seq) and quantitative PCR (qPCR). The results revealed that cyclooxygenase (COX) inhibition disrupted the renin-angiotensin system, leading to an accumulation of angiotensin II and cardiovascular developmental defects. Additionally, downregulation of the pla2 gene reduced substrates essential for COX enzyme activity, exacerbating the effects. Although NSAIDs are known to affect the digestive system, no significant effects on developmental factors were observed. RNA-Seq and qPCR analyses revealed an adaptive upregulation of key genes, including ace2 and cyp7a1 , involved in cardiovascular and metabolic regulation. Furthermore, 16S rRNA sequencing identified shifts in the microbial community, particularly in g_Rubritalea and g_Sphingomonas genera. Both the upregulated genes and the altered microbial taxa likely played a role in mitigating toxic effects and promoting homeostasis. Moreover, molecular docking suggested that MEX exhibited stronger sub-lethal effects than DCF, likely due to its higher binding affinity to COX. These findings provide valuable insights into NSAID toxicity mechanisms in marine fish, highlighting the importance of adaptive responses in countering environmental stress and underscoring the long-term ecological risks of chronic NSAID exposure.
研究领域:
海洋毒理学
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环境科学
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药理学
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分子生物学
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发育生物学
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生态毒理学
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微生物学
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生物信息学
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药物发现
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产品关联
DOI
PubMed
高影响因子
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