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Acta Biomaterialia · 2025 · IF 9.6

Ultrasound-activated directional and controllable nitric oxide therapy for vascular calcification repair through the modulation of eNOS/iNOS homeostasis

Chunxia Liu,Mengjing Lin,Jing Dai,Binglin Chen,Jiali Wang,Jingyi Li,Xiaoyun Li,Ziyun Jiang,Miao Xiao,Mingliang Tang

Vascular calcification (VC) is a critical pathological hallmark of cardiovascular diseases but current therapeutic options remain inadequate. Nitric oxide (NO) homeostasis plays a vital role in endothelial function and phenotypic transformation of vascular smooth muscle cells (VSMCs), two key pathological processes in VC. In this study, Fe₃O₄@PDA@BNN6 (FPB) nanoparticles were prepared for directional and controllable NO therapy. Magnetic field enriched the nanoparticles to the site of VC and ultrasound triggered the controllable release of NO to regulate the homeostasis of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), further activated sGC-cGMP-PKG signaling pathway. Both in the rat and in vitro VC models, the innovative therapy inhibited osteogenic like transformation of VSMCs, alleviated endothelial inflammatory response, regulated eNOS/iNOS homeostasis, and effectively improved VC. By ensuring optimal NO bioavailability for vascular homeostasis, this magneto-ultrasonically controlled strategy overcomes limitations of conventional NO-based therapies and paves the way for precision NO-mediated interventions in cardiovascular diseases. Statement of Significance Engineering innovation: Dual-modality nanoparticle system for precision NO delivery: Magnetic guidance directs the FPB to calcified lesions, reducing systemic off-target effects. Ultrasound-triggered release of NO to ensure on-demand delivery at VC sites. Mechanistic innovation: Restoring eNOS/iNOS homeostasis as a therapeutic axis: Directional and controllable NO therapy uniquely modulates eNOS/iNOS homeostasis, further activating the sGC-cGMP-PKG signaling pathway.

CAS / MDL: 62-31-7
研究领域: 心血管医学 · 纳米医学 · 分子治疗 · 生物医学工程 · 氧化还原生物学
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JOURNAL OF HAZARDOUS MATERIALS · 2024 · IF 12.2

Step-wise reproductive toxicities of imidazolium- and pyridinium-based ionic liquids on Caenorhabditis elegans

Jing Zhang,Chengcheng Lv,Zhenyang Yu,Yangyuan Zhou

Reproductive toxicities of imidazolium- ([EMIM]X) and pyridinium-based ([APYR]X) ionic liquids (ILs) are essential to fully assess their hazards. Presently, effects of five ILs on the intricate processes of reproduction, including sperm-oocyte interactions, were explored in Caenorhabditis elegans . Results showed that 1-ethylpyridinium bromide ([EPYR]Br) stimulated oocytes, zygotes and total reproduction. 1-Octylpyyridinium bromide ([OPYR]Br) inhibited oocytes and stimulated zygotes, it inhibited the initial and total reproduction. 1-Dodecylpyridinium bromide ([DPYR]Br) inhibited oocytes and zygotes, but stimulated the initial and total reproduction. 1-Ethyl-3-methylimidazolium bromide ([EMIM]Br) inhibited oocytes, but stimulated zygotes and reproduction. 1-Ethyl-3-methylimidazolium iodide ([EMIM]I) inhibited germcells and oocytes but stimulated zygotes and reproduction. Regarding hormones and lipid metabolism, the ILs commonly reduced main sperm protein, sperm transmembrane protein 9 and spermatocyte protein 8. The qRT-PCR results showed that the ILs commonly down-regulated the expressions of mpk-1 , while up-regulated those of inx-14 , with influences on the expressions of vab-1 , unc-43 and rme-2 . These biochemicals and genes were directly connected with the sperm-oocyte interactions. Transcriptomic analysis results supported the involvement of cAMP and cGMP-PKG signaling pathways underlying the effects on the sperm-oocyte interactions. The results also implied ILs’ impacts on neural and immune diseases and even cancers that should be considered in the future.

研究领域: 毒理学 · 生殖生物学 · 分子生物学 · 遗传学
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JOURNAL OF ETHNOPHARMACOLOGY · 2020 · IF 3.69

Laxative effect and mechanism of Tiantian Capsule on loperamide-induced constipation in rats

Tian Li,Mengmeng Hu,Cuihua Jiang,Dongjian Zhang,Meng Gao,Jianwei Xia,Mengqi Miao,Gaofeng Shi,Hui Li,Jian Zhang,Zhiqi Yin

Ethnopharmacological relevance Tiantian capsule (TTC), as a functional food, which consists of four herb medicines, including Aloe vera Burm.f. (25%), leaf juices, dried; Cucurbita moschata Duch. (25%), fructus, dried; Poria cocos (Schw.) Wolf. (12.5%), sclerotium, dried; Tremella fuciformis Berk. (12.5%), fruiting bodies, dried, and one extract xylooligosaccharides (25%) from Maize Cob by enzymolysis, has been commonly used in China to ameliorate constipation. Aim of the study The aim of the work is to elucidate the potential laxative mechanisms of TTC in loperamide-induced constipated rats. Materials and methods LC-MS/MS was employed for analyzing the TTC extract. The gastrointestinal transit was evaluated by X-ray. The H&E and Alcian-Blue stain were applied to determine the changes of goblet cells and mucus layer, respectively. Meanwhile, levels of neurotransmitters were evaluated by enzyme-linked immunosorbent assay. The protein expressions were also measured by immunohistochemistry and Western blot . Results Our results showed that TTC administration attenuated constipation responses in aspects of fecal pellets number, water content of feces, stomach emptying and gastrointestinal transit. Further investigations revealed that TTC treatment not only induced the recovery of neurotransmitters, such as motilin , substance P , somatostatin , endothelin and vasoactive intestinal peptide , but also up-regulated the expressions of c-kit and stem cell factor (SCF). Additionally, the number of goblet cells and thickness of the mucus layer were elevated, and the guanylate cyclase C-cGMP signal pathway was also up-regulated after TTC treatment. Conclusion Our findings demonstrated that the laxative effect of TTC in constipation rats is probably due to the regulation of bowel movement and intestinal fluid secretion.

CAS / MDL: 34552-83-5
研究领域: 药理学 · 胃肠病学 · 民族药理学
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ADVANCED FUNCTIONAL MATERIALS · 2023 · IF 19

Precipitation-Based Silk Fibroin Fast Gelling, Highly Adhesive, and Magnetic Nanocomposite Hydrogel for Repair of Irregular Bone Defects

Yan-Pei Zou,Hai-Feng Liang,Ben Wang,Qi-Chen Zhang,Di-Han Su,Shun-Yi Lu,Qian-Yi Zhang,Tao Wu,Lan Xiao,Yin Xiao,Jian Dong,Li-Bo Jiang,Xi-Lei Li

Critical-sized bone defects, especially for irregular shapes, remain a significant challenge in orthopedics. Although various biomaterials are developed for bone regeneration, their application for repair of irregular bone defects is limited by the complicated preparation procedures involved, and their lack of shape-adaptive capacity, physiological adhesion, and potent osteogenic bioactivity. In the present study, a simple strategy of precipitation by introducing tannic acid (TA) with abundant phenolic hydroxyl groups and Fe 3 O 4 nanoparticles, as metal-phenolic networks (MPN), is developed to easily prepare a fast gelling, shape-adaptive, and highly adhesive regenerated silk fibroin (RSF)/TA/Fe 3 O 4 hydrogel system that can respond to a static magnetic field (SMF). The RSF/TA/Fe 3 O 4 hydrogel exhibits sufficient adhesion in biological microenvironments and good osteogenic effect in vitro and in vivo, under an external SMF, and thus, can be applied to repair critical-sized bone defects. Moreover, bioinformatics analysis reveals that the synergistic mechanism of Fe 3 O 4 NPs and SMF on osteogenic effects can be promotion of osteoblast differentiation via activation of the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)/extracellular signal-regulated kinase (ERK) signaling pathway. This study provides a promising biomaterial with potential clinical application for the future treatment of (irregular) critical-sized bone defects.

CAS / MDL: 7440-25-7 25322-68-3
研究领域: 材料科学 · 生物医学工程 · 骨科 · 生物材料
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