Danyang Ye’s research while affiliated with Beijing University of Chinese Medicine and other places

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Publications (6)


Stigmast-4-en-3-one from Euonymus Alatus (Thunb.) Siebold. Improves Diabetic Retinopathy and Angiogenesis Mediated by Glucocorticoids Receptor
  • Article

July 2024

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11 Reads

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1 Citation

Journal of Ethnopharmacology

Ruifang Ji

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Yu Du

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Yong Wang

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[...]

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The process of Rat sarcoma (RAS) binding to plasma membrane after post‐translational modification. CAAX motifs at C‐terminal of RAS, consisting of cysteine, aliphatic amino acids, and a variable amino acid, help RAS localize to specific plasma membrane microdomains and subsequently pass signals to the downstream.³⁰ The post‐translational modification of CAAX is achieved by farnesylation, hydrolysis by RAS and a‐factor converting enzyme 1 (RCE1) and carboxymethylation by prenylcysteine carboxyl methyltransferase (pcCMT), followed by palmitoylation by palmitoyltransferases (PAT) in Golgi (harvey‐RAS (HRAS), neuroblastoma‐RAS (NRAS), KRAS4A). The difference between KRAS4B and other paralogs is that the CAAX of KRAS4B is able to bind to membrane depending on lysine residues.31,32 The figure was made using Biorender.
The frequency of RAS mutations in human cancers. The data come from TCGA PanCancer Atlas Studies. The activating mutations of RAS occur predominantly at codons 12, 13, and 61 and kirsten‐RAS (KRAS) has the most tendency to be mutated in the three paralogs. Clinically, RAS mutations are most prevalent in pancreatic adenocarcinoma (PC) (70%), colorectal cancer (CRC) (40%), and non‐small cell lung cancer (NSCLC) (30%). (A) PC; (B) colorectal adenocarcinoma; (C) lung adenocarcinoma; (D) uterine corpus endometrial adenocarcinoma; (E) uterine carcinosarcoma; (F) stomach adenocarcinoma; (G) testicular germ cell tumors; (H) cholangiocarcinoma; (I) cervical squamous cell carcinoma; (J) skin cutaneous melanoma; (K) acute myeloid leukemia; (L) thyroid carcinoma; (M) pheochromocytoma and paraganglioma; (N) thymoma.
Downstream signaling pathway of KRAS. After receiving the signal of epidermal growth factor, receptor tyrosine kinases (RTKs) such as EGFR will recruit RAS, targeting the membrane and activating it. Therefore, phosphorylation activation signals are passed in the downstream cascades, which contain the RAF–MEK–ERK, PI3K–protein kinase B (AKT), RAL, and TIAM1 pathways. These cascades regulate cell proliferation, migration, and invasion. The figure was made using Biorender.
RAS‐targeted cancer therapy: Advances in drugging specific mutations
  • Literature Review
  • Full-text available

May 2023

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197 Reads

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16 Citations

Rat sarcoma (RAS), as a frequently mutated oncogene, has been studied as an attractive target for treating RAS-driven cancers for over four decades. However, it is until the recent success of kirsten-RAS (KRAS)G12C inhibitor that RAS gets rid of the title "undruggable". It is worth noting that the therapeutic effect of KRASG12C inhibitors on different RAS allelic mutations or even different cancers with KRASG12C varies significantly. Thus, deep understanding of the characteristics of each allelic RAS mutation will be a prerequisite for developing new RAS inhibitors. In this review, the structural and biochemical features of different RAS mutations are summarized and compared. Besides, the pathological characteristics and treatment responses of different cancers carrying RAS mutations are listed based on clinical reports. In addition, the development of RAS inhibitors, either direct or indirect, that target the downstream components in RAS pathway is summarized as well. Hopefully, this review will broaden our knowledge on RAS-targeting strategies and trigger more intensive studies on exploiting new RAS allele-specific inhibitors.

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Synthesis, anti-aging and mechanism of magnolol derivatives

May 2023

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59 Reads

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2 Citations

Magnolol (M), a hydroquinone containing an allyl side chain, is one of the major active components of Houpoea officinalis for antioxidation and anti-aging. To enhance the antioxidant activity of magnolol, the different sites of magnolol were structurally modified in this experiment, and a total of 12 magnolol derivatives were obtained. Based on the preliminary exploration of the anti-aging effect of magnolol derivatives in a Caenorhabditis elegans (C. elegans) model. Our results indicate that the active groups of magnolol exerting anti-aging effects were allyl groups and hydroxyl on the phenyl. Meanwhile, the anti-aging effect of the novel magnolol derivative M27 was found to be significantly superior to that of magnolol. To investigate the effect of M27 on senescence and the potential mechanism of action, we investigated the effect of M27 on senescence in C. elegans. In this study, we investigated the effect of M27 on C. elegans physiology by examining body length, body curvature and pharyngeal pumping frequency. The effect of M27 on stress resistance in C. elegans was explored by acute stress experiments. The mechanism of M27 anti-aging was investigated by measuring ROS content, DAF-16 nuclear translocation, sod-3 expression, and lifespan of transgenic nematodes. Our results indicate that M27 prolonged the lifespan of C. elegans. Meanwhile, M27 improved the healthy lifespan of C. elegans by improving pharyngeal pumping ability and reducing lipofuscin accumulation in C. elegans. M27 increased resistance to high temperature and oxidative stress in C. elegans by reducing ROS. M27 induced DAF-16 translocation from cytoplasm to nucleus in transgenic TJ356 nematodes and upregulated the expression of sod-3 (a gene downstream of DAF-16) in CF1553 nematodes. Furthermore, M27 did not extend the lifespan of daf-16, age-1, daf-2, and hsp-16.2 mutants. This work suggests that M27 may ameliorate aging and extend lifespan in C. elegans through the IIS pathway.


Function and Inhibition of DYRK1A: emerging roles of treating multiple human diseases

March 2023

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32 Reads

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11 Citations

Biochemical Pharmacology

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is an evolutionarily conserved protein kinase and the most studied member of the Dual-specificity tyrosine-regulated kinase (DYRK) family. It has been shown that it participates in the development of plenty of diseases, and both the low or high expression of DYRK1A protein could lead to disorder. Thus, DYRK1A is recognized as a key target for the therapy for these diseases, and the studies on natural or synthetic DYRK1A inhibitors have become more and more popular. Here, we provide a comprehensive review for DYRK1A from the structure and function of DYRK1A, the roles of DYRK1A in various types of diseases, including diabetes mellitus, neurodegenerative diseases, and kinds of cancers, and the studies of its natural and synthetic inhibitors.


Exploring the anti-aging effects of chlorogenic acid and the underlying mechanisms based on a Caenorhabditis elegans model

February 2023

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16 Reads

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2 Citations

Journal of Traditional Chinese Medical Sciences

Objective: To explore the anti-aging effects of chlorogenic acid (CGA) and the underlying mechanisms based on a Caenorhabditis elegans (C. elegans) model. Methods: The anti-aging activity of CGA was studied based on the body length, exercise behavior, lipofuscin content, antioxidative stress ability, swallowing frequency, body-bending frequency, and head-swinging ability of C. elegans. Through DAF-16 nuclear translocation and SOD-3-GFP fluorescence experiments, the effects of CGA on ROS levels, antioxidant enzyme activities, MDA content, mutant-strain lifespan, and anti-aging molecular signaling pathways were explored, as well as the underlying mechanisms. Results: CGA improved multiple indices of the nematode: body length was increased (all P


Citations (3)


... Given the prevalence of RAS mutations and their impact on distant metastasis and mortality, developing effective targeted therapies against RAS or its downstream effectors could significantly improve outcomes for a substantial proportion of thyroid cancer patients [37]. While RAS itself has historically been considered "undruggable," recent advances in targeted therapies, including those targeting downstream effectors of RAS, offer promising avenues for exploration in thyroid cancer [38]. ...

Reference:

Decoding RAS mutations in thyroid cancer: A meta-analysis unveils specific links to distant metastasis and increased mortality
RAS‐targeted cancer therapy: Advances in drugging specific mutations

... To study the neuroprotective effects of pyrimido [4,5-b]indole derivatives, Loidreau and co-workers [106] synthesized a series of eighteen 4-pyrimidoindole derivatives, which were evaluated for their inhibition profile over the CDK5-p25 complex. In vitro, results revealed derivative 15 (Figure 7) as the most promising CDK5 inhibitor (IC 50 = 6 µM), being also capable to inhibit casein kinases CK1δ and CK1ε (IC 50 = 0.7 µM for both), two important kinases involved in cardiac signaling [107], and 1A kinase, that is regulated by double specificity tyrosine phosphorylation (DYRK1A, IC 50 = 3.1 µM) [106], mainly associated with diabetes pathogenesis [108]. ...

Function and Inhibition of DYRK1A: emerging roles of treating multiple human diseases
  • Citing Article
  • March 2023

Biochemical Pharmacology

... CGA can serve as a potential chemical chaperone and drug candidate for treatment of aggregation disorders. Recently the anti-aging potential of CGA has been observed [75]. Interaction Analysis of BSA, cyt c, and CGA Using Molecular Docking ...

Exploring the anti-aging effects of chlorogenic acid and the underlying mechanisms based on a Caenorhabditis elegans model
  • Citing Article
  • February 2023

Journal of Traditional Chinese Medical Sciences