Diagnostic accuracy of exhaled nitric oxide for the non-invasive identification of patients with fibrotic metabolic dysfunction-associated steatohepatitis

Article

作者: Zheng, Ming-Hua ; Chen, Sui-Dan ; Huang, Ou-Yang ; Targher, Giovanni ; Zhang, Huai ; Zhang, Xin-Lei ; Chen, Li-Li ; Zheng, Wen ; Zhang, Ni ; Jin, Xiao-Zhi ; Chen, Wen-Ying ; Byrne, Christopher D.

BACKGROUNDFibrotic metabolic dysfunction-associated steatohepatitis (MASH) is a condition at risk of progressing to advanced liver disease. We examined whether an innovative exhaled nitric oxide (eNO) breath test (BT) can accurately diagnose fibrotic MASH without requiring blood tests.METHODSOne hundred and forty-seven patients with MASH were recruited, and all tests were undertaken within 1 week of recruitment. With fibrotic MASH (NAS ≥ 4 and fibrosis stage ≥ 2) as the main outcome indicator, the diagnostic efficacy of eNO in identifying fibrotic MASH was compared to other validated models for advanced fibrosis requiring venesection, namely FAST, Agile 3⁺, and FIB-4 scores.RESULTSThe mean age was 40.36 ± 12.28 years, 73.5% were men. Mean body mass index was 28.83 ± 4.31 kg/m². The proportion of fibrotic MASH was 29.25%. The area under the receiver operating curve for eNO in diagnosing fibrotic MASH was 0.737 [95% CI 0.650-0.823], which was comparable to FAST (0.751 [0.656-0.846]), Agile 3⁺ (0.764 [0.670-0.858]), and FIB-4 (0.721 [0.620-0.821]) (all DeLong test p > 0.05). A cut-off of eNO <8.5 ppb gave a sensitivity of 86.0% and a negative predictive value of 88.5% for ruling-out fibrotic MASH. A cut-off of eNO >13.5 ppb provided a specificity of 91.3% and a positive predictive value of 65.4% for ruling-in fibrotic MASH. Sensitivity analyses demonstrated that the diagnostic efficacy of eNO was similar across characteristics such as age. Moreover, adding vibration-controlled transient elastography-LSM (liver stiffness measurement) reduced the uncertainty interval from 46.9% to 39.5%.CONCLUSIONSThe eNO-BT is a promising simple test for non-invasively identifying fibrotic MASH, and its performance is further improved by adding LSM measurement.

2024-12-01·European Journal of Medicinal Chemistry

Design, synthesis, and biological evaluation of novel iNOS inhibitors as potent neuroprotective agents for ischemic stroke

Article

作者: Tao, Mingshu ; Wu, Jianbing ; Huang, Zhangjian ; Kong, Tiantian ; Qu, Xiaohan ; Ji, Duorui ; Jin, Chengbin ; Zhang, Yihua ; Ye, Hui ; Chen, Huiqin ; Zhang, Libang ; Sun, Yuze ; Li, Hongyu

Ischemic stroke (IS) is characterized by intricate pathophysiological mechanisms, where single-target treatments have often proven insufficient. Thus, multi-target therapeutic approaches are essential for effective IS management. In this study, we employed a molecular hybridization strategy, merging the structures of the iNOS inhibitor 1400W and the multi-target neuroprotective agent NBP, to develop a series of novel iNOS inhibitors BN-1 ∼ BN-4 with neuroprotective properties. Among these, BN-4 exhibited the most potent cell protective activity in OGD/R-induced SH-SY5Y and BV-2 cells. BN-4 not only reduced ROS levels induced by OGD/R in SH-SY5Y cells but also mitigated necrosis and apoptosis. By binding to iNOS in a manner similar to 1400W, BN-4 significantly inhibited iNOS activity. Furthermore, BN-4 demonstrated high stability, excellent blood-brain barrier permeability, and more than 100-fold increase in aqueous solubility compared to NBP. Additionally, BN-4 notably decreased infarct size and showed neuroprotective effects in tMCAO rats. These findings indicate that BN-4 holds promise as a novel candidate for treatment IS, offering enhanced therapeutic efficacy due to its superior pharmacokinetic and pharmacodynamic properties.

2024-11-01·Current Drug Discovery Technologies

In-silico Studies, Synthesis, and Antacid Activities of Magnesium (II) Complexes

Article

作者: Jha, Basuki Nath ; Kothari, Richa ; Agrawal, Anurag

Background:Nowadays, acidity is a severe problem worldwide caused by excessive gastric acid secretion by the stomach and proximal intestine.Objective:Antacids are drugs capable of buffering stomach acid. Therefore, in our research work, we have reported the in-silico studies, synthesis, characterization, and evaluation of antacid activities of magnesium (II) complexes via the acid-base neutralization process.Methods:In this research, some magnesium complexes were synthesized and their antacid behavior was compared with marketed products. Also, in-silico studies were performed on H+/K+ ATPase (Proton pump). All synthesized compounds were characterized by various spectroscopic techniques like UV-Vis, FT-IR, XRD, and DSC techniques.Result:Spectroscopic analysis results showed that the semicarbazone ligand shows keto-enol isomerism and forms a coordinated stable complex with magnesium ions in the crystalline phase. The FT-IR results confirmed the presence of Mg-O stretching, N-H bending, and C=N stretching vibrations in Mg (II) complexes.Conclusion:The antacid activities of Mg (II) complexes were excellent as compared to the semicarbazone ligand and comparable with that of marketed antacid drugs like ENO, and Pantop-D. Insilco studies also confirmed that semicarbazone ligand and its Mg (II) complexes were both found to be fitted into the active sites of molecular targets, and Mg (II) complexes showed better binding affinities towards macromolecular as compared to semicarbazone ligand.

100 项与 FFSC-1 相关的药物交易

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