Evidence-based Complementary and Alternative Medicine
·
2019
·
IF 1.984
Liwen Han,Haotian Kong,Fasheng Liu,Xiaobin Li,Shanshan Zhang,Xuanming Zhang,Yong Wu,Hua Yang,Aiping Zhang,Kechun Liu
The aim of the study is to explore the protective effect of new gelatin (NG, Xin’ejiao in China) on hematopoietic injury caused by chemotherapy. Zebrafish, at 48 hours post fertilization (hpf), was treated with different chemotherapeutic drugs to establish the zebrafish hematopoietic damage model with reduced thrombocytes and erythrocytes. The protecting effects of NG on the thrombocytes and erythrocytes were observed, respectively, on zebrafish models. Then, the RT-PCR method was used to detect the change of mRNA level of the hematopoiesis-related cytokines scl1, c-myb, pu.1, GATA1, and runx1 genes. The results showed that 50 μg·mL−1 and 100 μg·mL−1 NG rescued and increased the thrombocytes numbers induced by vinorelbine (NVB) and chloramphenicol (CHL) and the erythrocytes numbers induced by methotrexate (MTX), doxorubicin (ADM), and mechlorethamine hydrochloride (MH) in zebrafish models. Meanwhile, the mRNA expression of scl1, c-myb, and GATA1 genes in the NG treatment group was raised compared with the MTX treatment group. Also, the mRNA expression of pu.1 and Runx1 in the NG treatment group was reduced compared with the MTX treatment group. In consequence, traditional Chinese medicine NG showed a certain degree protective effect on hematopoiesis injury induced by chemotherapy in this study, which may depend on the promotion of erythrocytes proliferation and the regulation of the hematopoietic genes level.
研究领域:
药理学
·
血液学
·
分子生物学
·
斑马鱼研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN
·
2021
·Vol. 144
·期 9
·2759-2770
·
IF 13.501
Zhang Yalun,Zhang Yi,Aman Yahyah,Ng Cheung Toa,Chau Wing-Hin,Zhang Zhigang,Yue Ming,Bohm Christopher,Jia Yizhen,Li Siwen,Yuan Qiuju,Griffin Jennifer,Chiu Kin,Wong Dana S M,Wang Binbin,Jin Dongyan,Rogaeva Ekaterina,Fraser Paul E,Fang Evandro F,St George-Hyslop Peter,Song You-Qiang
The molecular link between amyloid-β plaques and neurofibrillary tangles, the two pathological hallmarks of Alzheimer’s disease, is still unclear. Increasing evidence suggests that amyloid-β peptide activates multiple regulators of cell cycle pathways, including transcription factors CDKs and E2F1, leading to hyperphosphorylation of tau protein. However, the exact pathways downstream of amyloid-β-induced cell cycle imbalance are unknown. Here, we show that PAX6, a transcription factor essential for eye and brain development which is quiescent in adults, is increased in the brains of patients with Alzheimer’s disease and in APP transgenic mice, and plays a key role between amyloid-β and tau hyperphosphorylation. Downregulation of PAX6 protects against amyloid-β peptide-induced neuronal death, suggesting that PAX6 is a key executor of the amyloid-β toxicity pathway. Mechanistically, amyloid-β upregulates E2F1, followed by the induction of PAX6 and c-Myb, while Pax6 is a direct target for both E2F1 and its downstream target c-Myb. Furthermore, PAX6 directly regulates transcription of GSK-3β, a kinase involved in tau hyperphosphorylation and neurofibrillary tangles formation, and its phosphorylation of tau at Ser356, Ser396 and Ser404. In conclusion, we show that signalling pathways that include CDK/pRB/E2F1 modulate neuronal death signals by activating downstream transcription factors c-Myb and PAX6, leading to GSK-3β activation and tau pathology, providing novel potential targets for pharmaceutical intervention.
研究领域:
神经科学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2025
·
IF 3.3
Yulu Ru,Jiahui Chen,Qinxin Li,Qiyao Chen,Sihui Huang,Jiahuan Zhou,Dandan Wang,Xiaoshun Zhou,Yong Shao
Folding of nucleic acids is strongly dependent on metal ions. For example, G-quadruplex (G4) structures are usually determined by the specific K+/Na+ coordination. However, G4 constructs highly selective to high-valent metal ions (for instance, trivalent metal ions) have not been found due to their strong and nonspecific phosphate backbone interactions. Herein, a higher-order G4 structure having a heptad junction formed by GGA repeats (for example, GGA8 with eight repeats) of the human c-myb promoter region was found to stoichiometrically recruit three Tb3+ ions. The junction binding of Tb3+ did not affect the global G4 structure of GGA8 because of its high stability in K+. The three context A/A contacts with a proper stacking orientation and an appropriate interbase distance were proved to be the specific binding sites of Tb3+ (A/Tb3+/A). Other high-valent metal ions were unable to interfere with this specific Tb3+ binding, suggestive of the potential of GGA8 serving as an aptamer-like DNA for Tb3+. This A/Tb3+/A binding was also found in another KRAS promoter G4 structure with the same A/A contact, indicating the potential of Tb3+ in selectively probing G4 structures. This work will also inspire more interest in searching higher-order G4 structures for selectively coordinating high-valent metal ions with the purpose of their detection, enrichment, and recovery.
研究领域:
生物化学
·
分子生物学
·
无机化学
·
结构生物学
·
核酸研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）