Review
Medicine, Research & Experimental
Martina S. Savova, Liliya Mihaylova, Daniel Tews, Martin Wabitsch, Milen I. Georgiev
Summary: Obesity is a growing disorder that damages patients' quality of life and increases healthcare costs. Developing safe and innovative prevention strategies and treatments for obesity is crucial. The pathophysiology of obesity is complex and involves multiple signaling pathways, including the PI3K/AKT pathway, which plays a critical role in metabolic homeostasis. Natural compounds have been shown to target the PI3K/AKT signaling pathway and have potential for managing obesity. This paper evaluates the druggability of PI3K as a target and suggests perspectives on using natural compounds to modulate the PI3K/AKT pathway for obesity management.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Oncology
Huayi Li, Lorenzo Prever, Emilio Hirsch, Federico Gulluni
Summary: The PI3K signaling pathway is crucial in breast cancer and inhibitors targeting this pathway show promising activity, but resistance and adverse reactions limit their efficacy. Combination therapies and identifying suitable patient subpopulations are needed to enhance therapeutic benefit.
Article
Cell Biology
Jinhua Fang, Xiaoxi Sun, Silu Liu, Pu Yang, Jiangguo Lin, Jingjing Feng, Miguel A. Cruz, Jing-fei Dong, Ying Fang, Jianhua Wu
Summary: Our study found that VWF-induced platelet P-selectin translocation is triggered, accelerated, and enhanced by fluid shear stress, correlated with shear stress accumulation (SSA), and involves the PI3K/Akt axis. Force-triggered P-selectin translocation occurs quickly on partial platelet surface first and then gradually extends to the whole platelet surface as SSA increases. The GOF mutation (R1308L) promotes the process, while the LOF mutation (G1324S) slows it down.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hualin Chen, Lin Ma, Wenjie Yang, Yingjie Li, Zhigang Ji
Summary: POLR3G is highly expressed in bladder cancer and is associated with poor prognosis. Its deficiency inhibits migration and invasion of bladder cancer cells and reduces the expression of EMT-related markers. Mechanistically, POLR3G can promote EMT in bladder cancer by activating the PI3K/AKT signaling pathway.
Review
Biochemistry & Molecular Biology
Antonino Glaviano, Aaron S. C. Foo, Hiu Y. Lam, Kenneth C. H. Yap, William Jacot, Robert H. Jones, Huiyan Eng, Madhumathy G. Nair, Pooyan Makvandi, Birgit Geoerger, Matthew H. Kulke, Richard D. Baird, Jyothi S. Prabhu, Daniela Carbone, Camilla Pecoraro, Daniel B. L. Teh, Gautam Sethi, Vincenzo Cavalieri, Kevin H. Lin, Nathalie R. Javidi-Sharifi, Eneda Toska, Matthew S. Davids, Jennifer R. Brown, Patrizia Diana, Justin Stebbing, David A. Fruman, Alan P. Kumar
Summary: The PI3K/AKT/mTOR (PAM) signaling pathway plays a crucial role in cell survival, growth, and cell cycle progression. Dysregulation of this pathway is associated with cancer development and resistance to therapy. This review focuses on the major dysregulations in the PAM signaling pathway in cancer and discusses strategies for overcoming treatment resistance. The role of PAM signaling in immunology and immunotherapies is also discussed.
Article
Plant Sciences
Xiao-chen Li, Shuai Wang, Xin-xin Yang, Tian-jiao Li, Jia-xing Gu, Lin Zhao, Yong-rui Bao, Xian-sheng Meng
Summary: This study aimed to investigate the treatment of colorectal cancer (CRC) using Patrinia villosa Juss. (P.V) and clarify its underlying mechanism. The results from animal models showed that P.V can reduce tumor number and diameter, improve colon cell injury, and decrease levels of CRC biomarkers. Metabolomics analysis revealed changes in endogenous metabolites, indicating that P.V modulates the glycerol phospholipid metabolites closely related to the PI3K target and PI3K/Akt signaling pathway for CRC treatment.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Food Science & Technology
Huiying Li, Qianqian Yao, Chaonan Li, Linlin Fan, Haoming Wu, Nan Zheng, Jiaqi Wang
Summary: This study found that lactoferrin (LF) can suppress the development of colorectal cancer induced by type 2 diabetes (T2D) by regulating the NT5DC3 protein and the PI3K/AKT/mTOR signaling pathway. Further experiments confirmed that LF specifically binds to the NT5DC3 protein and activates its phosphorylation to inhibit T2D-induced colon tumor development, suggesting a new therapeutic strategy for cancer prevention.
Review
Pharmacology & Pharmacy
Amin Iranpanah, Leila Kooshki, Seyed Zachariah Moradi, Luciano Saso, Sajad Fakhri, Haroon Khan
Summary: As a major public health concern, neurological diseases and neurodegenerative diseases significantly impact the growing aging population, leading to disability and mortality. Apoptosis, inflammation, and oxidative stress play crucial roles in the development of neurodegenerative diseases, with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway being a key player. The blood-brain barrier poses challenges for drug delivery, but exosomes have emerged as potential nano-sized vehicles for central nervous system drug delivery due to their ability to cross the blood-brain barrier and their unique characteristics such as low immunogenicity and great tissue/cell penetration capabilities. This systematic review highlights the therapeutic potential of exosomes targeting the PI3K/Akt/mTOR signaling pathway in the context of neurodegenerative diseases and neurological diseases.
Article
Biochemistry & Molecular Biology
Li-Li Zhu, Gui-Yun Cao, Li-Ying Jia, Guo Zheng, Liang Zhang, Ping Sheng, Zhao-Qing Meng, Xin He, Chun-Feng Zhang, Chong-Zhi Wang, Chun-Su Yuan
Summary: This study investigated the cardioprotective effect of Muscone on AMI rats and found that Muscone significantly reduced myocardial injury, improved cardiac function, and exerted protective effects by inhibiting oxidative stress and apoptosis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Review
Cell Biology
Wuming Qin, Linghui Cao, Isaac Yaw Massey
Summary: Cardiac fibrosis is a common pathological change in heart failure and other cardiovascular diseases, with the PI3K/Akt signaling pathway playing a crucial role in regulating its occurrence, progression, and pathological formation.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Oncology
Qianxu Jin, Jiahui Zhao, Zijun Zhao, Shiyang Zhang, Zhimin Sun, Yunpeng Shi, Hongshan Yan, Yizheng Wang, Liping Liu, Zongmao Zhao
Summary: CAMK1D is expressed at lower levels in glioma tissues and is positively correlated with the WHO classification of gliomas. Knockdown of CAMK1D promotes the proliferation, migration, and invasion of glioma cells, while overexpression has the opposite effect. Mechanistically, CAMK1D regulates glioma cell function through the PI3K/AKT/mTOR pathway. These findings suggest that CAMK1D may serve as a prognostic predictor and a potential therapeutic target for glioma.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Maryam Akbarzadeh, Ainaz Mihanfar, Shabnam Akbarzadeh, Bahman Yousefi, Maryam Majidinia
Summary: The PI3K/AKT/mTOR signaling pathway plays a crucial role in cancer and has been found to interact with miRNAs, which is important for understanding cancer biology.
Article
Biotechnology & Applied Microbiology
Patricia K. Grueninger, Franziska Uhl, Heike Herzog, Gaia Gentile, Marta Andrade-Martinez, Tobias Schmidt, Kyuho Han, David W. Morgens, Michael C. Bassik, Michael L. Cleary, Oliver Gorka, Robert Zeiser, Olaf Gross, Jesus Duque-Afonso
Summary: B-cell precursor acute lymphoblastic leukemias (B-ALL) depend on the PI3K/AKT/MTOR signaling pathway, and the combined inhibition of MTOR and AKT shows a synergistic effect on decreased cell proliferation in B-ALL with different karyotypes. Changes in cell metabolism also disclose a possible target for combination therapy.
CANCER GENE THERAPY
(2022)
Review
Biochemistry & Molecular Biology
Chen Xue, Ganglei Li, Juan Lu, Lanjuan Li
Summary: Circular RNAs (circRNAs) are covalently closed noncoding RNAs that regulate target gene expression and play important roles in cancer progression through the circRNA/PI3K/AKT axis. Aberrant regulation of circRNA expression is significantly associated with clinicopathological characteristics and plays crucial roles in biological functions.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Cell Biology
Weipu Mao, Keyi Wang, Si Sun, Jianping Wu, Ming Chen, Jiang Geng, Ming Luo
Summary: The study revealed that ID2 serves as a tumor suppressor in bladder cancer, with high ID2 expression associated with lower tumor staging and better survival rates. Mechanistically, ID2 inhibits the progression and metastasis of BCa through the PI3K/AKT signaling pathway.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Biomedical
Zengsheng Chen, Jiafeng Zhang, Tieluo Li, Douglas Tran, Bartley P. Griffith, Zhongjun J. Wu
Article
Engineering, Biomedical
Robert G. Conway, Zachary B. Berk, Jiafeng Zhang, Tieluo Li, Douglas Tran, Zhongjun J. Wu, Bartley P. Griffith
Article
Engineering, Biomedical
Wenji Sun, Shigang Wang, Zengsheng Chen, Jiafeng Zhang, Tieluo Li, Katherin Arias, Bartley P. Griffith, Zhongjun J. Wu
Article
Engineering, Biomedical
Mehdi Nikfar, Meghdad Razizadeh, Jiafeng Zhang, Ratul Paul, Zhongjun J. Wu, Yaling Liu
Article
Biology
Liwei Wang, Zengsheng Chen, Jiafeng Zhang, Xiwen Zhang, Zhongjun J. Wu
BULLETIN OF MATHEMATICAL BIOLOGY
(2020)
Article
Cardiac & Cardiovascular Systems
Robert G. Conway, Jiafeng Zhang, Jean Jeudy, Charles Evans, Tieluo Li, Zhongjun Jon Wu, Bartley P. Griffith
Summary: In this study, the use of computational fluid dynamics and computed tomography angiography for analyzing thrombus formation in Quadrox D oxygenators was investigated. The results showed a well-defined pattern of clot burden in the oxygenators, consistent with the predicted values from computed tomography angiography. The study suggests that computed tomography angiography-based flow analysis is a valuable adjunct to computational fluid dynamics in understanding oxygenator thrombus formation.
Article
Engineering, Biomedical
Wenji Sun, Shigang Wang, Jiafeng Zhang, Katherin Arias, Bartley P. Griffith, Zhongjun J. Wu
Summary: This study investigated the effects of high mechanical shear stresses (HMSS) on neutrophils by exposing blood to different levels of HMSS. The results showed significant changes in surface receptor expression, increased phagocytic ability, but no significant change in transmigration capacity after exposure to HMSS.
Article
Engineering, Biomedical
Wenji Sun, Jiafeng Zhang, Aakash Shah, Katherin Arias, Zachary Berk, Bartley P. Griffith, Zhongjun J. Wu
Summary: The study demonstrated that pump-assisted circulation led to neutrophil activation, apoptosis, and functional impairment, which were strongly associated with pump operating condition and duration.
Article
Engineering, Biomedical
Ge He, Jiafeng Zhang, Aakash Shah, Zachary B. Berk, Lu Han, Han Dong, Bartley P. Griffith, Zhongjun J. Wu
Summary: The Breethe pump is a novel blood pump with improved biocompatibility to reduce common complications associated with current blood pumps. Computational and experimental data demonstrate that the Breethe pump has better hemolytic performance and washout quality compared to clinically accepted pumps like CentriMag and Rotaflow.
INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS
(2021)
Article
Engineering, Biomedical
Zachary B. K. Berk, Aakash Shah, Wenji Sun, Bartley P. Griffith, Zhongjun J. Wu
Summary: The study found that aPTT had a more reliable correlation to heparin concentration, particularly at lower concentrations, while the correlation between aPTT and ACT values was poor. Further in vivo studies are needed to confirm these results.
Article
Computer Science, Interdisciplinary Applications
Ge He, Lu Han, Jiafeng Zhang, Aakash Shah, David J. Kaczorowski, Bartley P. Griffith, Zhongjun Wu
Summary: LVADs are increasingly used for end-stage heart failure patients, but associated with thromboembolic events. FSI simulation in this study evaluated the effect of LVAD IC orientation on LV hemodynamics, finding that IC towards the MV may reduce the risk of thrombus formation.
COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Mark F. Pittenger, Saman Eghtesad, Pablo G. Sanchez, Xiaoyan Liu, Zhongjun Wu, Ling Chen, Bartley P. Griffith
Summary: Pretreating MSCs with agents that block apoptotic pathways improves their in vivo survival, leading to improved cardiac function in a myocardial infarct model. This approach has implications for MSC-based cardiac therapies and other indications where increased cell survival is desired.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Biomedical
Katherin Arias, Wenji Sun, Shigang Wang, Erik N. Sorensen, Erika Feller, David Kaczorowski, Bartley Griffith, Zhongjun J. Wu
Summary: This study found a direct link between the severity of acquired platelet defects and NSB in CF-LVAD recipients, with the occurrence of NSB being associated with platelet activation and receptor reduction.
Article
Engineering, Biomedical
Dong Han, Jiafeng Zhang, Ge He, Bartley P. Griffith, Zhongjun J. Wu
Summary: This study developed a new pediatric ECMO system, called PPL, which has excellent biocompatibility and gas exchange performance. Computational and experimental data showed that the PPL's oxygenator has significantly low pressure drop and better hemolysis performance. The PPL has the potential to provide blood pumping and respiratory support for a wide range of pediatric patients.
Article
Engineering, Biomedical
Dong Han, Wenji Sun, Kiersten P. Clark, Bartley P. Griffith, Zhongjun J. Wu
Summary: High levels of non-physiological shear stress mainly activate platelets by enhancing the vWF-GPIb alpha interaction. Shear-induced platelet activation and receptor shedding occur through distinct pathways.