The combination of machine learning and transcriptomics reveals a novel megakaryopoiesis inducer, MO-A, that promotes thrombopoiesis by activating FGF1/FGFR1/PI3K/Akt/NF-κB signaling

Zhang, Ting; Mo, Qi; Jiang, Nan; Wu, Yuesong; Yang, Xin; Chen, Wang; Li, Qinyao; Yang, Shuo; Yang, Jing; Zeng, Jing; Huang, Feihong; Huang, Qianqian; Luo, Jiesi; Wu, Jianming; Wang, Long

doi:10.1016/j.ejphar.2023.175604

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…An increased possibly of PTN/NCL interaction between Fibros and Endos in the DKD group was likely to regulate angiogenic activities and promote PTN-induced Endo migration [46]. Our results suggest that diabetes significantly induced the activity of the fibroblast growth factor 1 (FGF1)/FGFR1 axis, which has been reported to be involved in thrombopoiesis, activating NF-κB, and metastasis through EMT [47][48][49]. We also observed an increase in the number of pathways between Fibros and Endos via VEGFD_VEGFR3, VEGFD_VEGFR2R3, and TGFB1/3_(TGFB1+TGFB2) in the DKD group.…”

Section: Cell-cell Interactions During Dkd and Pb5 Treatmentmentioning

confidence: 70%

Single-cell RNA sequencing reveals the effects of hederasaponin C in the treatment of diabetic nephropathy

Liu,

Zhang,

Zhao

et al. 2023

Acta Materia Medica

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There is great demand for the development of novel efficient therapeutic strategies or preventative measures to alleviate the life-threatening complications of type 2 diabetes. Hederasaponin C (PB5), a natural product, has been reported to exhibit significant therapeutic effects in various diseases; however, the possible effects and mechanism underlying PB5 in reducing diabetic renal complications have not been comprehensively reported. Here, we investigated the response of murine diabetic models to PB5 treatment using single-cell RNA-sequencing (scRNA-seq) and proteomics. Our findings revealed the dynamic transcriptional changes of renal cells in response to diabetic nephropathy. PB5 alleviated inflammatory injury by partially reducing pathophysiologic processes. In addition, we observed severe glomerular lesions and functional deficiencies, including GBM thickening and podocyte dysfunction, during the progression of diabetes, which were likewise attenuated by PB5. These results provide insight into how PB5 treatment improves diabetic symptoms and possibly serves as a novel protective measure and therapeutic strategy in the treatment of type 2 diabetes.

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Section: Cell-cell Interactions During Dkd and Pb5 Treatmentmentioning

confidence: 70%

Single-cell RNA sequencing reveals the effects of hederasaponin C in the treatment of diabetic nephropathy

Liu,

Zhang,

Zhao

et al. 2023

Acta Materia Medica

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“…In our previous work, our team utilized a naive Bayesian algorithm to construct a drug activity prediction model aimed at screening for compounds that can enhance MK differentiation and platelet production. This model identified methylophiopogonanone A as a potential therapeutic agent for RIT, demonstrating its ability to enhance MK differentiation and platelet production [ 17 ]. Additionally, our team screened wedelolactone, a compound promoting MK differentiation, using hybrid recurrent neural network (RNN) and DNN models [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

An Innovative Inducer of Platelet Production, Isochlorogenic Acid A, Is Uncovered through the Application of Deep Neural Networks

Yi,

Luo,

Liao

et al. 2024

Biomolecules

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(1) Background: Radiation-induced thrombocytopenia (RIT) often occurs in cancer patients undergoing radiation therapy, which can result in morbidity and even death. However, a notable deficiency exists in the availability of specific drugs designed for the treatment of RIT. (2) Methods: In our pursuit of new drugs for RIT treatment, we employed three deep learning (DL) algorithms: convolutional neural network (CNN), deep neural network (DNN), and a hybrid neural network that combines the computational characteristics of the two. These algorithms construct computational models that can screen compounds for drug activity by utilizing the distinct physicochemical properties of the molecules. The best model underwent testing using a set of 10 drugs endorsed by the US Food and Drug Administration (FDA) specifically for the treatment of thrombocytopenia. (3) Results: The Hybrid CNN+DNN (HCD) model demonstrated the most effective predictive performance on the test dataset, achieving an accuracy of 98.3% and a precision of 97.0%. Both metrics surpassed the performance of the other models, and the model predicted that seven FDA drugs would exhibit activity. Isochlorogenic acid A, identified through screening the Chinese Pharmacopoeia Natural Product Library, was subsequently subjected to experimental verification. The results indicated a substantial enhancement in the differentiation and maturation of megakaryocytes (MKs), along with a notable increase in platelet production. (4) Conclusions: This underscores the potential therapeutic efficacy of isochlorogenic acid A in addressing RIT.

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“…Flow cytometry analysis of cells in vivo were performed as described previously ( Zhang et al, 2023 ). Briefly, PB, BM, and spleen cells were examined by flow cytometry using the BD FACSCanto II flow cytometer (BD Biosciences, San Jose, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia

Zhou,

Ni,

Liao

et al. 2024

eLife

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Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induces the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of VLZ. The effects of Vilazodone (VLZ) on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blotting and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo . The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

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The combination of machine learning and transcriptomics reveals a novel megakaryopoiesis inducer, MO-A, that promotes thrombopoiesis by activating FGF1/FGFR1/PI3K/Akt/NF-κB signaling

Cited by 10 publications

References 33 publications

Single-cell RNA sequencing reveals the effects of hederasaponin C in the treatment of diabetic nephropathy

Single-cell RNA sequencing reveals the effects of hederasaponin C in the treatment of diabetic nephropathy

An Innovative Inducer of Platelet Production, Isochlorogenic Acid A, Is Uncovered through the Application of Deep Neural Networks

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia

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