Frontiers in Pharmacology
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2022
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IF 5.988
Wang Yiran,Shi Jihua,Dai Dapeng,Cai Jianping,Wang Shuanghu,Hong Yun,Zhou Shan,Zhao Fangling,Zhou Quan,Geng Peiwu,Zhou Yunfang,Xu Xue,Luo Qingfeng
As a novel acid-suppressing drug, vonoprazan shows the potential to replace traditional proton-pump inhibitors. With its widespread use, some adverse effects that require further study have emerged due to drug–drug interactions. Our study is the first experiment that evaluated the drug–drug interactions of eleven common cardiovascular drugs that inhibit vonoprazan metabolism in vitro and in vivo. Rat liver microsome incubation and molecular simulation docking were applied to explore the inhibition mechanism. Amlodipine and nifedipine showed inhibitory effects on vonoprazan metabolism in both rat and human liver microsomes in the first evaluation part in vitro. The inhibition mechanism analysis results demonstrated that amlodipine and nifedipine might inhibit the metabolism of vonoprazan by a mixed type of competitive and non-competitive inhibition. However, the pharmacokinetic data of the vonoprazan prototype revealed that amlodipine affected vonoprazan in vivo while nifedipine did not. Thus, more attention should be paid when amlodipine is prescribed with vonoprazan. Furthermore, the changes in its carboxylic acid metabolites MI hinted at a complex situation. Molecular simulation suggested the CYP2B6 enzyme may contribute more to this than CYP3A4, and further inhibitory experiments preliminarily verified this speculation. In conclusion, the use of vonoprazan with cardiovascular drugs, especially amlodipine, should receive particular attention in clinical prescriptions.
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JOURNAL OF FOOD COMPOSITION AND ANALYSIS
·
2023
·
IF 4.3
Qinglin Wang,Hao Yuan,Xinyue Pan,Yiling Yang,Xiaosong Ma,Yahui Guo
The purpose of this study was to explore the feasibility and mechanism of synthesizing silver nanoclusters (AgNCs) using a double-stranded DNA (dsDNA) template and to use the AgNCs as probes for captopril detection. The results showed that the binding of silver ions towards DNA bases deduced the destruction of the initial dsDNA structure , and AgNCs with decent quantum yield (43.54%) were obtained. The detection using these AgNCs probes showed good performance for captopril , with a linear range of 0.1–0.8 μg·mL −1 and a detection limit of 0.045 μg·mL −1 . Recovery results in real samples of Apocynum venetum leaf tea and Ginkgo biloba leaf tablet demonstrated its good applicability. This work not only extended the understanding of DNA-AgNCs but also provided a fast and cost-effective tool for captopril detection.
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Frontiers in Pharmacology
·
2021
·
IF 5.811
Liu Tao,Cui Lijuan,Xue Huan,Yang Xiaohua,Liu Mengmeng,Zhi Linping,Yang Huanhuan,Liu Zhihong,Zhang Min,Guo Qing,He Peifeng,Liu Yunfeng,Zhang Yi
Angiotensin II type 1 (AT1) receptor blockers (ARBs), as antihypertensive drugs, have drawn attention for their benefits to individuals with diabetes and prediabetes. However, the direct effects of ARBs on insulin secretion remain unclear. In this study, we aimed to investigate the insulinotropic effect of ARBs and the underlying electrophysiological mechanism. We found that only telmisartan among the three ARBs (telmisartan, valsartan, and irbesartan) exhibited an insulin secretagogue role in rat islets. Independent of AT1 receptor and peroxisome proliferator-activated receptor γ (PPARγ), telmisartan exerted effects on ion channels including voltage-dependent potassium (Kv) channels and L-type voltage-gated calcium channels (VGCCs) to promote extracellular Ca2+ influx, thereby potentiating insulin secretion in a glucose-dependent manner. Furthermore, we identified that telmisartan directly inhibited Kv2.1 channel on a Chinese hamster ovary cell line with Kv2.1 channel overexpression. Acute exposure of db/db mice to a telmisartan dose equivalent to therapeutic doses in humans resulted in lower blood glucose and increased plasma insulin concentration in OGTT. We further observed the telmisartan-induced insulinotropic and electrophysiological effects on pathological pancreatic islets or β-cells isolated from db/db mice. Collectively, our results establish an important insulinotropic function of telmisartan distinct from other ARBs in the treatment of diabetes.
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HISTOLOGY AND HISTOPATHOLOGY
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2024
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IF 2.5
Zhou Hua,Jiuhong Deng,Guiying Wang
Objective: Diabetic nephropathy (DN) is a prevalent cause of end-stage kidney disease worldwide. Moringa isothiocyanate-1 (MIC-1) has shown potential for DN management, however, the exact mechanisms remain unclear. This research intended to evaluate the impact and mechanism of MIC-1 on DN. Methods: Six C57BLKS/J-db/m mice served as controls. Eighteen C57BLKS/J-db/db mice were randomly separated into three groups: db/db, db/db + irbesartan (IBS), and db/db + MIC-1. Three weeks post-drug administration, the body weight and kidney weight of mice in each group were measured. Concurrently, serum creatinine (Scr), urine albumin, insulin, glycosylated hemoglobin (GHb), oxidative stress-, and inflammatory-related factors were determined. Additionally, the pathological injury, apoptosis, apoptosis-related markers, NLRP3, and ASC levels in the kidney tissues were examined utilizing H&E, Masson, PAS, TUNEL staining, and Western blot. Results: MIC-1 decreased the body weight, kidney weight, the levels of Glu, Scr, and urine albumin in db/db mice. Moreover, MIC-1 significantly suppressed the levels of MDA, insulin, GHb, TNF-α, IL-1β, and IL-6, while increased the activities of SOD, CAT, and GPX in the serum of db/db mice. MIC-1 also mitigated the kidney tissue injury in db/db mice. Western blot assay showed that MIC-1 enhanced the Bcl-2 level and suppressed the Bax, cleaved caspase-3, cleaved caspase-9, NLRP3, ASC, and caspase-1 levels of the kidney tissues in db/db mice. Conclusions: MIC-1 ameliorated the kidney injury in DN mice, and its mechanism may be associated with the suppression of renal cell apoptosis, oxidative stress, and inflammatory responses.
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Cell Reports
·
2025
·Vol. 44
·期 12
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IF 6.9
Yunfei Zhou,Xinxin Yang,Jianwen Xu,Yidi Wu,Yin Fu,Yihong Dong,Xun Yang,Qiang Fu,Chenxu Guo,Yunjing Hou,Shuyuan Chang,Jun Yan,Ju Ran,Yumeng Wang,Qingxin Zhang,Tomii Ayaka,Lei Yu,Feng Geng,Liuyang Zhao,Xiaoyang Hu,Shuijie Li,Hongxue Meng,Dabin Liu
Dysregulated cholesterol synthesis fuels cancer progression, but its precise role in hepatocellular carcinoma (HCC) remains unclear. Here, we identify elevated acetylation of 24-dehydrocholesterol reductase (DHCR24) at Lys254 as a hallmark of HCC. Both total DHCR24 and its K254 acetylation independently predict poor patient survival. Acetylation stabilizes DHCR24, sustaining hepatic cholesterol synthesis and promoting tumorigenesis. Mechanistically, DHCR24 acetylation enhances 7-ketocholesterol accumulation, which upregulates p62 and drives HCC growth in vitro and in vivo . Pharmacologic inhibition of DHCR24 expression and acetylation with the US Food and Drug Administration (FDA)-approved drug irbesartan suppresses cell proliferation and reduces tumor burden in xenograft and carcinogen-induced mouse models. Reduced p62 expression parallels the antitumor effects. These findings define DHCR24 acetylation as a metabolic switch linking sterol synthesis to oncogenesis and highlight the DHCR24-7-ketocholesterol-p62 axis as a therapeutic target for HCC.
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