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eNOS/NO通路
CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Mild low-temperature photothermal therapy demonstrated a distinctive 'hot spring' effect in the multichannel regulation of atherosclerosis instead of inducing foam cell apoptosis

Jie Sheng,Ziyue Zu,Jianchen Qi,Yugang Zhang,Haoguang Wu,Zhicheng Wang,Yu Miao,Tao Zheng,Sheng Wang,Linlin Zhang,Guangming Lu,Longjiang Zhang

Atherosclerosis (AS), characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause adverse cardiovascular events. However, effectively addressing all these pathological conditions simultaneously is challenging. To devise a comprehensive treatment strategy for AS, we developed a nanoparticle-based mild photothermal therapy (PTT) approach, which controlled the temperature within the range of 42–45 ℃, creating a unique 'hot spring' effect. The nanoparticles used in this therapy consist of a core made of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with indocyanine green (IR820), and an outer shell made of L-arginine (LA)-modified polydopamine (PDA), which is further modified with hyaluronic acid (HA) to target plaques. In vitro studies have demonstrated that mild PTT can open the TRPV1 channel in foam cells and regulate lipid metabolic diseases by maintaining a controlled temperature range of 42–45 ℃. Furthermore, the LA-PDA shell has anti-inflammatory properties, decreasing NLRP3 expression. Moreover, the eNOS/NO pathway was activated by LA, promoting the healing of injured endothelial cells (ECs). Additionally, the increased temperature enhances HSP90 expression, thereby helping to maintain eNOS.  In vivo studies further confirmed that the HLPIZ-guided ‘hot spring’ effect has impressive anti-atherosclerotic capability by scavenging lipids, reducing inflammation, and repairing injured ECs simultaneously. In conclusion, our study confirmed that HLPIZ-guided mild PTT can exhibit a ‘hot spring’ effect, effectively regulating three key pathophysiological processes of AS, being a novel, potentially effective strategy for anti-AS therapy.

研究领域: 心血管疾病 · 纳米技术 · 治疗策略 · 炎症 · 脂质代谢
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Bioactive Materials · 2022 · IF 16.874

Wireless electrical stimulation at the nanoscale interface induces tumor vascular normalization

Changhao Li,Cairong Xiao,Lizhen Zhan,Zhekun Zhang,Jun Xing,Jinxia Zhai,Zhengnan Zhou,Guoxin Tan,Jinhua Piao,Yahong Zhou,Suijian Qi,Zhengao Wang,Peng Yu,Chengyun Ning

Pathological angiogenesis frequently occurs in tumor tissue, limiting the efficiency of chemotherapeutic drug delivery and accelerating tumor progression. However, traditional vascular normalization strategies are not fully effective and limited by the development of resistance. Herein, inspired by the intervention of endogenous bioelectricity in vessel formation, we propose a wireless electrical stimulation therapeutic strategy, capable of breaking bioelectric homeostasis within cells, to achieve tumor vascular normalization. Polarized barium titanate nanoparticles with high mechano-electrical conversion performance were developed, which could generate pulsed open-circuit voltage under low-intensity pulsed ultrasound. We demonstrated that wireless electrical stimulation significantly inhibited endothelial cell migration and differentiation in vitro . Interestingly, we found that the angiogenesis-related eNOS/NO pathway was inhibited, which could be attributed to the destruction of the intracellular calcium ion gradient by wireless electrical stimulation. In vivo tumor-bearing mouse model indicated that wireless electrical stimulation normalized tumor vasculature by optimizing vascular structure, enhancing blood perfusion, reducing vascular leakage, and restoring local oxygenation. Ultimately, the anti-tumor efficacy of combination treatment was 1.8 times that of the single chemotherapeutic drug doxorubicin group. This work provides a wireless electrical stimulation strategy based on the mechano-electrical conversion performance of piezoelectric nanoparticles, which is expected to achieve safe and effective clinical adjuvant treatment of malignant tumors.

研究领域: 生物医学工程 · 肿瘤学 · 纳米技术 · 超声治疗 · 血管生物学
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Frontiers in Pharmacology · 2024 · IF 4.4

Black ginseng: a novel medicine for treating heart failure

Dou Peiyuan,Liu Linlin,Jin Mozhu,Huang Jing,Lekhooa Rose Makhotso,Ran Xiaoku,Yan Xiaohui

Introduction: Black ginseng (BG) was processed by “steaming and drying” (generally nine times) repeatedly to produce “rare saponins” and secondary ginsenosides. Both ginseng (GS) and red ginseng (RG) were commonly used in treating heart failure (HF), and the latter was confirmed to be more potent, implying the presence of rare ginsenosides that contribute positively to the treatment of heart failure. Previous research indicated that rare ginsenosides are more abundant in BG than in RG. Consequently, this study aims to investigate the effects of BG and its components on HF to elucidate the active substances and their underlying mechanisms in the treatment of HF.Methods: The effects of BG and its fractions (water-eluted fraction (WEF), total saponin fraction (TSF), and alcohol-eluted fraction (AEF)) on rats with isoproterenol (ISO)-induced HF were explored, and steroids belonging to the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axes were determined quantitatively using the ultra-performance liquid chromatography–triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method. In addition, 16S rDNA sequencing was performed on the gut microbiota, followed by GC–MS analysis of short-chain fatty acids (SCFAs), and the biochemical indexes related to energy metabolism and the serum cyclic nucleotide system were also analyzed by ELISA.Results: Based on a thorough evaluation of energy metabolism and the endocrine system, it was observed that the effects of BG components on the hypothalamic–pituitary–thyroid (HPT) and HPA axes were more pronounced. Notably, the treatment efficacy of the low dose of the total saponin fraction (TSFL), water decoction (WD), and high dose of the polysaccharide fraction (PSFH) was superior based on pharmacodynamic indicators such as brain natriuretic peptide (BNP), creatine kinase (CK), and estradiol (E2)/T). Furthermore, the WD and BG components exhibited significant effects on androgens (T and androstenedione (A4)). The TSFL group exerts an anti-inflammatory effect by regulating Lactobacillus/Erysipelotrichales. The WD, PSFH, and TSFL may impact inflammatory cytokines through the gut microbiota (Lactobacillus/Erysipelotrichales) and their metabolites (acetate and butyrate), exerting an anti-inflammatory effect.Discussion: The BG and all its split components demonstrated varying levels of efficacy in alleviating HF, and TSF and PSF exhibited a significant protective effect on HF. The main active components in TSF were revealed to be ginsenosides Rk1, Rk3, 20-(S)-Rg3, and 20-(S)-Rh2 by the H9C2 cell experiment. The decoction of BG and its components exhibited a potent impact on androgen hormones, with an elevation trend. This phenomenon may be attributed to the activation of the eNOS-NO pathway through androgen regulation, thereby contributing to its anti-HF activities. The WD, PSFH, and TSFL may exert anti-inflammatory effects through the intestinal flora (Lactobacillaceae/Erysipelotrichaceae) and its metabolites (acetic acid and butyric acid), which affect the inflammatory factors. The different mechanisms of action of each component of HF also reflect the significance and necessity of the overall role of traditional Chinese medicine (TCM). Our research was the first to report that the E2/T is related to HF and can be used as an indicator to evaluate HF.

研究领域: 药理学 · 心脏病学 · 传统中药 · 内分泌学 · 微生物学 · 代谢组学
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