Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.

Purpose: The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA. Methods: Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology. Results: We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1. Conclusion: Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.

Diagnostic performance of RASSF1A and SHOX2 methylation combined with EGFR mutations for differentiation between small pulmonary nodules.

BACKGROUND AND AIM: Aberrant methylation of Ras association domain family 1, isoform A (RASSF1A), and short-stature homeobox gene 2 (SHOX2) promoters has been validated as a pair of valuable biomarkers for diagnosing early lung adenocarcinomas (LUADs). Epidermal growth factor receptor (EGFR) is the key driver mutation in lung carcinogenesis. This study aimed to investigate the aberrant promoter methylation of RASSF1A and SHOX2, and the genetic mutation of EGFR in 258 specimens of early LUADs. METHODS: We retrospectively selected 258 paraffin-embedded samples of pulmonary nodules measuring 2 cm or less in diameter and evaluated the diagnostic performance of individual biomarker assays and multiple panels between noninvasive (group 1) and invasive lesions (groups 2A and 2B). Then, we investigated the interaction between genetic and epigenetic alterations. RESULTS: The degree of RASSF1A and SHOX2 promoter methylation and EGFR mutation was significantly higher in invasive lesions than in noninvasive lesions. The three biomarkers distinguished between noninvasive and invasive lesions with reliable sensitivity and specificity: 60.9% sensitivity [95% confidence interval (CI) 52.41-68.78] and 80.0% specificity (95% CI 72.14-86.07). The novel panel biomarkers could further discriminate among three invasive pathological subtypes (area under the curve value > 0.6). The distribution of RASSF1A methylation and EGFR mutation was considerably exclusive in early LUAD (P = 0.002). CONCLUSION: DNA methylation of RASSF1A and SHOX2 is a pair of promising biomarkers, which may be used in combination with other driver alterations, such as EGFR mutation, to support the differential diagnosis of LUADs, especially for stage I.

Molecular Insights into Curvature Effects on the Capacitance of Electrical Double Layers in Tricationic Ionic Liquids with Carbon Nanotube Electrodes.

Ionic liquid (IL) electrolytes and carbon nanotube (CNT) electrodes have exhibited promising electrochemical performance in supercapacitors. Nevertheless, the adaptability of tricationic ILs (TILs) in CNT-based supercapacitors remains unknown. Herein, the performance of supercapacitors with (6,6), (8,8), (12,12), and (15,15) CNT electrodes in the TIL [C6(mim)3](Tf2N)3 was assessed via molecular dynamics simulations, paying attention to the electric double-layer (EDL) structures and the relations between the CNT curvature and capacitance. The results disclose that counterion and co-ion number densities near CNT electrodes have a marked reduction, compared with that of the graphene electrode. The capacitance of the EDL in the TIL increases significantly as the CNT curvature increases and the capacitance of the TIL/CNT systems is higher than that of the TIL/graphene system. Moreover, different EDL structures in the TIL and the monocationic IL (MIL) [C6mim][Tf2N] near CNT electrodes were revealed, showing higher-concentration anions [Tf2N]- at the CNT surfaces in the TIL. It is also verified that the TIL has a greater energy-storage ability under high potentials. Furthermore, the almost flat or weakly camel-like capacitance-voltage (C-V) curve of EDLs in the TIL turns into a bell shape in the MIL, because of the ion accumulation at the CNT surfaces and the associations between ions.

[Research advance in multi-component pharmacokinetics of Chinese herbal extracts in recent five years].

The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.

[Effects of transient cerebral ischemia and reperfusion injury on expression of aquaporin-4 and apoptosis in hippocampal neurons of aged animals: experiment with rats].

OBJECTIVE: To investigate the effects of transient cerebral ischemia and reperfusion injury on brain edema and apoptosis hippocampal neurons of aged animals. METHODS: 120 19-21-month-old healthy Wistar rats underwent four-vessel occlusion to establish whole cerebral ischemia model and were randomly divided into 3 equal groups to undergo ischemia for 1 min, 3 min, and 5 min respectively. Every group was re-divided into 5 equal sub-groups to undergo reperfusion for 12 h, 1 d, 2 d, 3 d, and 7 d respectively. Another 40 rats underwent sham operation to be used as controls. At different reperfusion time points 4 rats from each subgroup were killed to measure the wet and dry weights of the hippocampus. The brains of the remaining 4 rats from each subgroup underwent HE staining and microscopy. The expression of aquaporin-4 (AQP4) was detected by SABC immunohistochemical technique, and the neuron apoptosis in hippocampus was detected by TUNEL method. RESULTS: There was no significant differences in brain water content and expression of AQP4 between the ischemia 1 min and 3 min subgroups and the corresponding sham-operation subgroups (all P > 0.05), however, the brain water contents and AQP4 expression levels of the ischemia 5 min subgroups were all significantly higher than those of the corresponding sham-operation subgroups (all P < 0.05). There were only a few TUNEL-positive cells in the sham-operation subgroups and ischemia 1 min subgroups, however, the numbers of TUNEL-positive cells of the ischemia 3 min and 5 min subgroups were all significantly higher. The number of TUNEL-positive cells raised 12 h after ischemia, peaked 1 day after, and began to go down 3 days later. CONCLUSION: The aged animals are more sensitive to cerebral ischemia/reperfusion injury, and transient cerebral ischemia may cause brain edema, and increase of apoptotic cells and AQP4 expression. Neuron apoptosis is more sensitive to cerebral ischemia than brain edema and AQP4 expression. After reperfusion neuron apoptosis peaks earlier and lasts longer in the aged animals.