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学者姓名:王娟
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Abstract :
Aloperine is an alkaloid found in the seeds and leaves of the medicinal plant Sophora alopecuroides L. It has been used as herbal medicine in China for centuries due to its potent anti-inflammatory, antioxidant, antibacterial, and antiviral properties. Recently, aloperine has been widely investigated for its therapeutic activities. Aloperine is proven to be an effective therapeutic agent against many human pathological conditions, including cancer, viral diseases, and cardiovascular and inflammatory disorders. Aloperine is reported to exert therapeutic effects through triggering various biological processes, including cell cycle arrest, apoptosis, autophagy, suppressing cell migration, and invasion. It has also been found to be associated with the modulation of various signaling pathways in different diseases. In this review, we summarize the most recent knowledge on the modulatory effects of aloperine on various critical biological processes and signaling mechanisms, including the PI3K, Akt, NF-kappa B, Ras, and Nrf2 pathways. These data demonstrate that aloperine is a promising therapeutic candidate. Being a potent modulator of signaling mechanisms, aloperine can be employed in clinical settings to treat various human disorders in the future.
Keyword :
autophagy autophagy Ras Ras PI3K/Akt PI3K/Akt cell cycle cell cycle Nrf2 Nrf2 NF-kappa B NF-kappa B apoptosis apoptosis
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GB/T 7714 | Tahir, Muhammad , Ali, Sakhawat , Zhang, Wenting et al. Aloperine: A Potent Modulator of Crucial Biological Mechanisms in Multiple Diseases [J]. | BIOMEDICINES , 2022 , 10 (4) . |
MLA | Tahir, Muhammad et al. "Aloperine: A Potent Modulator of Crucial Biological Mechanisms in Multiple Diseases" . | BIOMEDICINES 10 . 4 (2022) . |
APA | Tahir, Muhammad , Ali, Sakhawat , Zhang, Wenting , Lv, Boqiang , Qiu, Wenge , Wang, Juan . Aloperine: A Potent Modulator of Crucial Biological Mechanisms in Multiple Diseases . | BIOMEDICINES , 2022 , 10 (4) . |
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Abstract :
Autophagy is an evolutionarily conserved pathway, in which cytoplasmic components are sequestered within double-membrane vesicles called autophagosomes and then transported into lysosomes or vacuoles for degradation. Over 40 conserved autophagy-related (ATG) genes define the core machinery for the five processes of autophagy: initiation, nucleation, elongation, closure, and fusion. In this review, we focus on one of the least well-characterized events in autophagy, namely the closure of the isolation membrane/phagophore to form the sealed autophagosome. This process is tightly regulated by ESCRT machinery, ATG proteins, Rab GTPase and Rab-related proteins, SNAREs, sphingomyelin, and calcium. We summarize recent progress in the regulation of autophagosome closure and discuss the key questions remaining to be addressed.
Keyword :
closure closure isolation membrane isolation membrane autophagosome autophagosome autophagy autophagy
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GB/T 7714 | Jiang, Wenyan , Chen, Xuechai , Ji, Cuicui et al. Key Regulators of Autophagosome Closure [J]. | CELLS , 2021 , 10 (11) . |
MLA | Jiang, Wenyan et al. "Key Regulators of Autophagosome Closure" . | CELLS 10 . 11 (2021) . |
APA | Jiang, Wenyan , Chen, Xuechai , Ji, Cuicui , Zhang, Wenting , Song, Jianing , Li, Jie et al. Key Regulators of Autophagosome Closure . | CELLS , 2021 , 10 (11) . |
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Abstract :
To obtain new anticancer agents with antimetastatic adjunct efficacy, a series of novel N-4-hydrazone derivatives of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one were designed and synthesized by an eight-step reaction, with appropriate yields. All the synthesized compounds were evaluated for their antiproliferative activity against A549 and MCF-7 cells and for antiplatelet aggregation activity in vitro. The results showed that compounds 25 and 35 not only showed potent antiproliferative activity against the A549 (IC50 = 15.3 and 21.4 mu M) and MCF-7 (IC50 = 15.6 and 10.9 mu M) cell lines but also showed certain antiplatelet aggregation activity (inhibition rates: 47.0% and 45.8%). These results indicated that the structural modification on the N-4-hydrazone moiety of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one is promising to obtain novel anticancer compounds with antimetastatic adjunct efficacy. In addition, a molecular docking study was performed to investigate the possible targets, and these results indicated that compounds 25 and 35 have the potential to target EGFR, HER2, and P2Y(12).
Keyword :
antimetastatic antimetastatic 3-d]pyrimidin-6-one 3-d]pyrimidin-6-one anticancer anticancer synthesis synthesis hydrazone hydrazone pyrrolo[2 pyrrolo[2
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GB/T 7714 | Zhao, Zhichang , Wang, Hongjun , Tian, Nana et al. Synthesis and biological evaluation of N-4-hydrazone derivatives of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one as novel anticancer agents with antimetastatic adjunct efficacy [J]. | ARCHIV DER PHARMAZIE , 2021 , 354 (11) . |
MLA | Zhao, Zhichang et al. "Synthesis and biological evaluation of N-4-hydrazone derivatives of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one as novel anticancer agents with antimetastatic adjunct efficacy" . | ARCHIV DER PHARMAZIE 354 . 11 (2021) . |
APA | Zhao, Zhichang , Wang, Hongjun , Tian, Nana , Yan, Hong , Wang, Juan . Synthesis and biological evaluation of N-4-hydrazone derivatives of 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one as novel anticancer agents with antimetastatic adjunct efficacy . | ARCHIV DER PHARMAZIE , 2021 , 354 (11) . |
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Abstract :
Autophagy is a conserved degradation process crucial to maintaining the primary function of cellular and organismal metabolism. Impaired autophagy could develop numerous diseases, including cancer, cardiomyopathy, neurodegenerative disorders, and aging. N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells, and the fate of m6A modified transcripts is controlled by m6A RNA binding proteins. m6A modification influences mRNA alternative splicing, stability, translation, and subcellular localization. Intriguingly, recent studies show that m6A RNA methylation could alter the expression of essential autophagy-related (ATG) genes and influence the autophagy function. Thus, both m6A modification and autophagy could play a crucial role in the onset and progression of various human diseases. In this review, we summarize the latest studies describing the impact of m6A modification in autophagy regulation and discuss the role of m6A modification-autophagy axis in different human diseases, including obesity, heart disease, azoospermatism or oligospermatism, intervertebral disc degeneration, and cancer. The comprehensive understanding of the m6A modification and autophagy interplay may help in interpreting their impact on human diseases and may aid in devising future therapeutic strategies.
Keyword :
m6A m6A Azoospermatism Azoospermatism RNA methylation RNA methylation Cancer Cancer Autophagy Autophagy Obesity Obesity Ischemic heart disease Ischemic heart disease
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GB/T 7714 | Chen, Xuechai , Wang, Jianan , Tahir, Muhammad et al. Current insights into the implications of m6A RNA methylation and autophagy interaction in human diseases [J]. | CELL AND BIOSCIENCE , 2021 , 11 (1) . |
MLA | Chen, Xuechai et al. "Current insights into the implications of m6A RNA methylation and autophagy interaction in human diseases" . | CELL AND BIOSCIENCE 11 . 1 (2021) . |
APA | Chen, Xuechai , Wang, Jianan , Tahir, Muhammad , Zhang, Fangfang , Ran, Yuanyuan , Liu, Zongjian et al. Current insights into the implications of m6A RNA methylation and autophagy interaction in human diseases . | CELL AND BIOSCIENCE , 2021 , 11 (1) . |
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Abstract :
Autophagy starts with the initiation and nucleation of isolation membranes, which further expand and seal to form autophagosomes. The regulation of isolation membrane closure remains poorly understood. CK1 delta is a member of the casein kinase I family of serine/threonine specific kinases. Although CK1 delta is reported to be involved in various cellular processes, its role in autophagy is unknown. Here, we show that CK1 delta regulates the progression of autophagy from the formation of isolation membranes to autophagosome closure, and is essential for macroautophagy. CK1 delta depletion results in impaired autophagy flux and the accumulation of unsealed isolation membranes. The association of LC3 with ATG9A, ATG14L, and ATG16L1 was found to be increased in CK1 delta-depleted cells. The role of CK1 delta in autophagosome completion appears to be conserved between yeasts and humans. Our data reveal a key role for CK1 delta/Hrr25 in autophagosome completion.
Keyword :
isolation membrane isolation membrane CK1 delta CK1 delta autophagosome closure autophagosome closure autophagy autophagy Hrr25 Hrr25
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GB/T 7714 | Li, Yuting , Chen, Xuechai , Xiong, Qianqian et al. Casein Kinase 1 Family Member CK1 delta/Hrr25 Is Required for Autophagosome Completion [J]. | FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY , 2020 , 8 . |
MLA | Li, Yuting et al. "Casein Kinase 1 Family Member CK1 delta/Hrr25 Is Required for Autophagosome Completion" . | FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 8 (2020) . |
APA | Li, Yuting , Chen, Xuechai , Xiong, Qianqian , Chen, Yong , Zhao, Hongyu , Tahir, Muhammad et al. Casein Kinase 1 Family Member CK1 delta/Hrr25 Is Required for Autophagosome Completion . | FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY , 2020 , 8 . |
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Abstract :
Purpose Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and ranked top in terms of incidence and mortality in men and women. Recently, improvements in treatment approaches for NSCLC have reported, but still, there is a need to devise innovative treatment strategies, especially to manage the advanced and metastatic stage of NSCLC. Aloperine (ALO), an herbal alkaloid, has exerted anti-cancer effects in many cancers. However, the use of any chemotherapeutic agents is dose limited due to possible adverse effects and drug-resistance issues. Therefore, a combination of chemotherapy with viral-based targeted gene therapy may provide a novel treatment strategy for NSCLC. Methods/results In this study, the results of the MTT and flow cytometry-based assays showed that Aloperine-Adbic (adenoviral vector expressing p14(ARF)/p53) combined treatment on NSCLC cells synergistically produced anti-proliferative effects, induced apoptosis, and arrested cell cycle at the G1 phase. Furthermore, the expression analysis suggested that the p53/p21 pathway might contribute to achieving aforesaid cytotoxic effects. The ALO-Adbic combined treatment prolonged the percent survival of NSCLC xenograft models. Conclusion In conclusion, ALO-Adbic combination can produce synergistic anti-cancer effects at low doses, and may offer a more effective and less toxic new treatment strategy for NSCLC.
Keyword :
NSCLC NSCLC Aloperine Aloperine Adenoviral vectors Adenoviral vectors p53 p53 Synergy Synergy
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GB/T 7714 | Muhammad, Tahir , Sakhawat, Ali , Khan, Aamir Ali et al. Aloperine in combination with therapeutic adenoviral vector synergistically suppressed the growth of non-small cell lung cancer [J]. | JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY , 2020 , 146 (4) : 861-874 . |
MLA | Muhammad, Tahir et al. "Aloperine in combination with therapeutic adenoviral vector synergistically suppressed the growth of non-small cell lung cancer" . | JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 146 . 4 (2020) : 861-874 . |
APA | Muhammad, Tahir , Sakhawat, Ali , Khan, Aamir Ali , Huang, Hua , Khan, Haroon Rashid , Huang, Yinghui et al. Aloperine in combination with therapeutic adenoviral vector synergistically suppressed the growth of non-small cell lung cancer . | JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY , 2020 , 146 (4) , 861-874 . |
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Abstract :
N-6-Methyladenosine (m6A) is the most prevalent internal modification that occurs in the mRNA of eukaryotes and plays a vital role in the post-transcriptional regulation. Recent studies highlighted the biological significance of m6A modification in the nervous system, and its dysregulation has been shown to be related to degenerative and neurodevelopmental diseases. Parkinson's disease (PD) is a common age-related neurological disorder with its pathogenesis still not fully elucidated. Reports have shown that epigenetic mechanisms including DNA methylation and histone acetylation, which alter gene expression, are associated with PD. In this study, we found that global m6A modification of mRNAs is down-regulated in 6-OHDA-induced PC12 cells and the striatum of PD rat brain. To further explore the relationship mechanism of PD, we decreased m6A in dopaminergic cells by overexpressing between m6A mRNA methylation and molecular a nucleic acid demethylase, FTO, or by m6A inhibitor. The results showed that m6A reduction could induce the expression of N-methyl-D-aspartate (NMDA) receptor 1, and elevate oxidative stress and Ca2+ influx, resulting in dopaminergic neuron apoptosis. Collectively, m6A modification may play a vital role in the death of dopaminergic neuron, which provides a novel view of mRNA methylation to understand the epigenetic regulation of Parkinson's disease.
Keyword :
oxidative stress oxidative stress mRNA methylation mRNA methylation NMDAR1 NMDAR1 Parkinson's disease Parkinson's disease FTO FTO 6-methyladenine 6-methyladenine
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GB/T 7714 | Chen, Xuechai , Yu, Chunyu , Guo, Minjun et al. Down-Regulation of m6A mRNA Methylation Is Involved in Dopaminergic Neuronal Death [J]. | ACS CHEMICAL NEUROSCIENCE , 2019 , 10 (5) : 2355-2363 . |
MLA | Chen, Xuechai et al. "Down-Regulation of m6A mRNA Methylation Is Involved in Dopaminergic Neuronal Death" . | ACS CHEMICAL NEUROSCIENCE 10 . 5 (2019) : 2355-2363 . |
APA | Chen, Xuechai , Yu, Chunyu , Guo, Minjun , Zheng, Xiaotong , Ali, Sakhawat , Huang, Hua et al. Down-Regulation of m6A mRNA Methylation Is Involved in Dopaminergic Neuronal Death . | ACS CHEMICAL NEUROSCIENCE , 2019 , 10 (5) , 2355-2363 . |
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