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CHINESE JOURNAL OF CHEMISTRY · 2022 ·Vol. 41 ·期 2 ·199-206 · IF 5.56

HPDA/Zn as a CREB Inhibitor for Ultrasound Imaging and Stabilization of Atherosclerosis Plaque†

Linzi Chen,Zhenqi Jiang,Lifei Yang,Ye Fang,Shuwei Lu,Ozioma U. Akakuru,Shuaishuai Huang,Juan Li,Suya Ma,Aiguo Wu

Comprehensive Summary Thrombosis, secondary to rupture of unstable plaque, is a fatal risk factor for myocardial infarction and ischemic stroke. At present, more novel methods are needed for the diagnosis and treatment of vulnerable plaque. Here, we report a hollow polydopamine/Zn (HPDA/Zn) ultrasound contrast agent. Through western-blot, Elisa, and other experiments, we found that in addition to having a good contrast-enhancement capability in ultrasound imaging in vitro and in vivo , HPDA/Zn also has the effect of reducing the expression of CREB. CREB protein and its downstream-regulated proteins and factors are closely related to the stability of plaque. HPDA/Zn has the effect of reducing the expression of CREB protein, which leads to the decrease of expression of MMP-9, the regulatory protein downstream of the CREB protein. In addition, it also reduces the secretion of inflammatory factors hs-CRP and IL-17A. Thus, HPDA/Zn can stabilize plaque by inhibiting CREB and reducing plaque vulnerable markers and inflammatory factors. In a word, HPDA/Zn is a kind of ultrasound contrast agent, which can stabilize plaques by inhibiting CREB protein.

CAS / MDL: 62-31-7
研究领域: 医学影像 · 心血管疾病 · 药理学 · 生物医学工程
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APPLIED AND ENVIRONMENTAL MICROBIOLOGY · 2020 ·Vol. 86 ·期 19 · IF 4.016

3-Hydroxypyridine Dehydrogenase HpdA Is Encoded by a Novel Four-Component Gene Cluster and Catalyzes the First Step of 3-Hydroxypyridine Catabolism in Ensifer adhaerens HP1

Haixia Wang,Xiaoyu Wang,Hao Ren,Xuejun Wang,Zhenmei Lu

3-Hydroxypyridine (3HP) is an important natural pyridine derivative. Ensifer adhaerens HP1 can utilize 3HP as its sole sources of carbon, nitrogen, and energy to grow, but the genes responsible for the degradation of 3HP remain unknown. In this study, we predicted that a gene cluster, designated 3hpd, might be responsible for the degradation of 3HP. The analysis showed that the initial hydroxylation of 3HP in E. adhaerens HP1 was catalyzed by a four-component dehydrogenase (HpdA1A2A3A4) and led to the formation of 2,5-dihydroxypyridine (2,5-DHP). In addition, the SRPBCC component in HpdA existed as a separate subunit, which is different from other SRPBCC-containing molybdohydroxylases acting on N-heterocyclic aromatic compounds. Moreover, the results demonstrated that the phosphoenolpyruvate (PEP)-utilizing protein and pyruvate-phosphate dikinase were involved in the HpdA activity, and the presence of the gene cluster 3hpd was discovered in the genomes of diverse microbial strains. Our findings provide a better understanding of the microbial degradation of pyridine derivatives in nature and indicated that further research on the origin of the discovered four-component dehydrogenase with a separate SRPBCC domain and the function of PEP-utilizing protein and pyruvate-phosphate dikinase might be of great significance.IMPORTANCE 3-Hydroxypyridine is an important building block for the synthesis of drugs, herbicides, and antibiotics. Although the microbial degradation of 3-hydroxypyridine has been studied for many years, the molecular mechanisms remain unclear. Here, we show that 3hpd is responsible for the catabolism of 3-hydroxypyridine. The 3hpd gene cluster was found to be widespread in Actinobacteria, Rubrobacteria, Thermoleophilia, and Alpha-, Beta-, and Gammaproteobacteria, and the genetic organization of the 3hpd gene clusters in these bacteria shows high diversity. Our findings provide new insight into the catabolism of 3-hydroxypyridine in bacteria.

CAS / MDL: 5154-01-8
研究领域: 微生物学 · 生物化学 · 分子生物学 · 环境科学
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JOURNAL OF NANOBIOTECHNOLOGY · 2025 · IF 12.6

HPDA-based tubule-targeting nanoplatform alleviates oxidative stress and ferroptosis for the reversal of renal interstitial fibrosis

Zheng Xiao,Peng Luo,Guoli Li,Huifang Tan,Chen Zhou,Dong Zeng,Yinyin Chen,Ying Li

Background: Renal interstitial fibrosis (RIF) is a hallmark pathological process in the progression of chronic kidney disease (CKD). However, effective therapies to halt or reverse RIF remain limited. Emerging evidence implicates ferroptosis as a critical contributor to RIF. Rosiglitazone (Rosi), a widely used thiazolidinedione, exhibits anti-ferroptotic activity but suffers from poor aqueous solubility, limited renal specificity, and systemic side effects. Results: Here, we constructed a renal tubular epithelial cell-targeted nano-based drug delivery system-Rosi-loaded, K3 peptide-modified, PEGylated hollow polydopamine(HPDA) nanoparticles (Rosi@HPDA-PEG-K3 NPs). This system displayed excellent biocompatibility and lesion-specific targeting, achieving prolonged retention in fibrotic kidneys. The in vitro and in vivo experiment demonstrated that this nano-based drug delivery system inhibited ferroptosis through downregulation of ACSL4, iron ion chelation, and ROS scavenging. Concurrently, it stabilized mitochondrial membrane potential and synergistically suppressed inflammatory responses, ultimately attenuating RIF. Conclusions: In summary, Rosi@HPDA-PEG-K3 NPs deliver Rosi specifically to renal renal tubular epithelial cells(TECs)and exert an anti-RIF effect through the integration of ferroptosis inhibition, mitochondrial protection, and inflammation modulation. Our study establishes a nanotherapeutic platform with precise targeting and multifunctional efficacy, highlighting its scientific rigor and the clinical translational potential of RIF.

研究领域: 纳米医学 · 肾脏病学 · 药学 · 分子生物学 · 生物医学工程
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