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Preclinical, Journal: HO-1 mediated by PI3K/Akt/Nrf2 signaling pathway is involved in (-)-epigallocatechin-3-gallate-rescueing impaired cognitive function induced by chronic cerebral hypoperfusion in rat model. (Pubmed Central) - Sep 20, 2022 Furthermore, EGCG treatment induced the expression of PI3K, p-Akt, Nrf2, and HO-1 protein, and they were partly reversed by the LY294002, siRNA-Nrf2, or ZnPP. EGCG has a neuroprotective effect on rat impaired cognition induced by CCH, possibly by modulating the PI3K/AKT/Nrf2/HO-1 pathway.
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Journal: Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 Cells. (Pubmed Central) - Sep 18, 2022 Meanwhile, pretreatment with LY294002 (a specific PI3K inhibitor) suppresses the phosphorylation of eNOS and NO production...Overall, the present study uncovers a novel effect of SFN to stimulate eNOS activity in EA.hy926 cells by regulating NO bioavailability. These findings provide clear evidence that SFN regulates eNOS activity and NO bioavailability, suggesting a promising therapeutic candidate to prevent endothelial dysfunction, atherosclerosis and other cardiovascular diseases.
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Journal: MicroRNA-155 expression is associated with pulpitis progression by targeting SHIP1. (Pubmed Central) - Sep 14, 2022 Taken together, these results indicate that H S ameliorated U-triggered NRK-52 cells pyroptosis via upregulation of PI3K/AKT/mTOR pathway, suggesting a novel role for H S in the management of nephrotoxicity caused by U exposure. Our data revealed a novel role for miR-155 in regulation of dental pulpal inflammatory response by targeting SHIP1 through PI3K/AKT signaling pathway.
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Preclinical, Journal: Establishment of a Mouse Submandibular Salivary Gland Organ Culture. (Pubmed Central) - Sep 14, 2022 Preventing pathological crosstalk between atrial myocytes and fibroblasts may be a novel target to ameliorate atrial fibrosis in patients with AF. We also describe the use of environmental stress (hypoxic stimulation) and inhibitors (U0126, LY294002, and rapamycin) to elucidate signaling pathways involved in salivary gland development.
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Journal: Tongqiao Mingmu formula alleviates retinal ganglion cell autophagy through PI3K/AKT/mTOR pathway. (Pubmed Central) - Sep 14, 2022 However, TQMM formula serum could generate an opposite effect and upregulate the expressions of the PI3K/AKT/mTOR pathway genes and proteins. In conclusion, the TQMM formula can prevent glutamate-induced autophagy in RGCs, possibly by activating the PI3K/AKT/mTOR pathway and reducing the expression of autophagy-related biomarkers LC3 and Belicin-1 to attenuate autophagy and maintain RGC viability.
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Journal: CB2 receptor activation inhibits the phagocytic function of microglia through activating ERK/AKT-Nurr1 signal pathways. (Pubmed Central) - Sep 10, 2022 Using ERK1/2 inhibitor U0126 and PI3K/AKT inhibitor LY294002, we revealed that the amount of Nurr1 in the nucleus was upregulated through β-arrestin2/ERK1/2 and PI3K/AKT/GSK-3β signaling pathways...Pretreatment with the signaling pathway inhibitors, especially U0126, reversed the inhibitory effect of 2-AG on phagocytosis, suggesting that CB2 receptor may regulate the phagocytic function of microglia by activating Nurr1. In conclusion, CB2 receptor or/and Nurr1-mediated signal pathways play instrumental roles in the progress of phagocytosis, which are expected to open up new treatment strategies for neurodegenerative diseases.
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Preclinical, Journal: Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways. (Pubmed Central) - Sep 10, 2022 We showed that preadministration of the PI3K inhibitor LY294002 abolished the repressive effect of ghrelin on CTA memory...Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin's effect...By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways.
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Preclinical, Journal: Acupuncture Improves Endometrial Angiogenesis by Activating PI3K/AKT Pathway in a Rat Model with PCOS. (Pubmed Central) - Sep 7, 2022 Acupuncture was performed every other day for 15 days, and the PI3K inhibitor (LY294002) was intraperitoneal injected 30 mins before acupuncture treatment...The efficacy of acupuncture on a rat model with PCOS was counteracted by the combination with the PI3K inhibitor. Acupuncture improves endometrial angiogenesis by activating the PI3K/AKT pathway, thus promoting endometrial receptivity and the number of implantation sites in rats with PCOS.
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Journal, IO biomarker: Lutein attenuated methylglyoxal-induced oxidative damage and apoptosis in PC12 cells via the PI3K/Akt signaling pathway. (Pubmed Central) - Aug 27, 2022 Furthermore, LY294002, a specific PI3K inhibitor, partially abolished the protective effect of lutein...This article confirmed a protective effect of lutein on oxidative damage and apoptosis in PC12 cells after MGO damage. These results indicated that lutein could potentially be developed as a nutraceutical or functional food in the prevention of diabetic-related neurodegenerative diseases.
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Journal, IO biomarker: Silicon-substituted calcium phosphate promotes osteogenic-angiogenic coupling by activating the TLR4/PI3K/AKT signaling axis. (Pubmed Central) - Aug 22, 2022 However, although LY294002 can achieve the same inhibitory effect as TLR4 siRNA by blocking the PI3K/AKT signaling pathway, it could not affect the expression of TLR4...In conclusion, we have elucidated the role of TLR4/PI3K/AKT signaling axis in Si-CaP mediated osteogenic-angiogenic coupling for the first time. This study provides new data onto the regulatory role and molecular mechanism of Si-CaP in the process of osteogenic-angiogenic coupling, which strongly supports its wide application for bone tissue engineering.
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Journal: Role of PI3K in the bone resorption of apical periodontitis. (Pubmed Central) - Aug 22, 2022 This study provides new data onto the regulatory role and molecular mechanism of Si-CaP in the process of osteogenic-angiogenic coupling, which strongly supports its wide application for bone tissue engineering. Under the inflammatory environment induced by LPS, PI3K participates in the occurrence and development of chronic apical periodontitis by regulating the proliferation and differentiation of osteoclasts and osteoblasts.
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Journal: Cornuside Is a Potential Agent against Alzheimer's Disease via Orchestration of Reactive Astrocytes. (Pubmed Central) - Aug 22, 2022 In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.
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Journal: rhEPO Upregulates the PPARγ Pathway in Long-term Cultured Primary Nerve Cells via PI3K/Akt to Delay Cell Senescence. (Pubmed Central) - Aug 18, 2022 Previous studies have confirmed that both recombinant human erythropoietin (rhEPO) and peroxisome proliferator-activated receptors γ (PPARγ) activator pioglitazone can protect senescent nerve cells, and their mechanisms involve enhancing cell antioxidant capacity and reducing cell apoptosis...Starting on the 11th day of culture, rhEPO, LY294002, and GW9662 were added for treatment...In conclusion, this study confirmed that rhEPO can upregulate the expression of PGC-1α and PPARγ in cells and the level of PPARγ protein in the nucleus to enhance the antioxidant capacity of cells and delay the senescence of nerve cells through the PI3K/Akt pathway. These findings will provide ideas for finding new targets for neuroprotection research and will also provide a theoretical basis and experimental evidence for rhEPO anti-aging research in neural cells.
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Preclinical, Journal: PDZK1 upregulates nitric oxide production through the PI3K/ERK2 pathway to inhibit porcine circovirus type 2 replication. (Pubmed Central) - Aug 17, 2022 A PI3K inhibitor (LY294002) and a NO synthase inhibitor (L-NAME hydrochloride) decreased the activity of PDZK1 in restricting PCV2 replication...PDZK1 affected IL-4 expression through the PI3K/ERK2 pathway, but PDZK1 modulation of PCV2 replication occurred independently of IL-4. Our results contribute to understanding the biological functions of PDZK1 and provide a theoretical basis for the pathogenic mechanisms of PCV2.
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Journal: Crosstalk between PI3K/Akt and Wnt/β-catenin pathways promote colorectal cancer progression regardless of mutational status. (Pubmed Central) - Aug 17, 2022 In addition, these effects were hindered after pretreatment with LY294002, a specific PI3K inhibitor, suggesting some dependence between these two signaling cascades. Our findings show that, regardless of mutational status, there is an interplay between the activity of PI3K/Akt and Wnt/β-catenin pathways that contributes to events related to CRC progression and that the reversal of such events using a PI3K inhibitor highlights the value of targeting these pathways for potential directed therapies in CRC patients.
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