- |||||||||| Journal: Allicin suppressed Escherichia coli-induced urinary tract infections by a novel MALT1/NF-κB pathway. (Pubmed Central) - Apr 5, 2022
Moreover, in rats with an E. coli-induced UTI model, allicin significantly alleviated the infection and up-regulation of MALT1 expression in the bladders, a marked increase in the bacterial load of urine, and deviations in serum biochemical parameters. In conclusion, allicin exerts anti-infective effects in UTIs mainly via the MALT1/NF-κB axis or AKT/NF-κB pathway, which provides a theoretical basis for understanding the function of allicin against UTIs and facilitates its clinical application.
- |||||||||| Journal: Fengreqing Oral Liquid Exerts Anti-Inflammatory Effects by Promoting Apoptosis and Inhibiting PI3K/AKT and NF-κB Signaling Pathways. (Pubmed Central) - Apr 5, 2022
In LPS-induced ALI mice, FOL administration showed inhibition of IL-1β, IL-6, and TNF-α in Bronchoalveolar lavage fluid (BALF) and decreased protein expression levels of PI3K, AKT, NF-κB p50, and NF-κB p65, and elevated protein expression levels of Bax and cleaved-caspase-3 significantly. These results suggest that FOL may exert anti-inflammatory effects by inhibiting the PI3K/AKT signaling pathway to promote apoptosis and leading to attenuated activation of the NF-κB signaling pathway.
- |||||||||| RSL3 / Stanford University
Preclinical, Journal: Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via Ferroptosis. (Pubmed Central) - Apr 5, 2022 On the other hand, the protective role of ASIV can be abrogated by RSL3 to some extent...However, Pi3K inhibitor LY294002 abrogated these activations. In conclusion, ferroptosis may involve in ADR-induced nephrotoxicity, and ASIV might protect nephrocytes against ADR-induced ferroptosis, perhaps via activations of the Pi3K/Akt and Nrf2 signaling pathways.
- |||||||||| cisplatin / Generic mfg., temozolomide / Generic mfg.
Journal, IO biomarker: The Role of m5C-Related lncRNAs in Predicting Overall Prognosis and Regulating the Lower Grade Glioma Microenvironment. (Pubmed Central) - Apr 5, 2022 The high-risk group was more sensitive to anti-CTLA4 therapy and to compounds including Temozolomide, Bleomycin, Cisplatin, Cyclopamine, A.443654 (Akt inhibitor), AZD6482 (PI3K inhibitor), GDC0941(PI3K inhibitor), and metformin. We present for the first time a m5C-related lncRNA signature for lower grade glioma patient prognosis and therapy response prediction with validated performance, providing a promising target for future research.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Quercetin inhibits AQP1 translocation in high-glucose-cultured SRA01/04 cells through PI3K/Akt/mTOR Pathway. (Pubmed Central) - Apr 1, 2022 Quercetin significantly decreased the AQP1 elevation and prevented the change of AQP1 location through inhibiting the activation of the PI3K/Akt/mTOR signaling in high-glucose-cultured SRA01/04 cells, which might have the preventable and inhibitory effects on the early development of diabetic cataract. The specific pathophysiological role of quercetin still needs to be verified.
- |||||||||| LY294002 / Eli Lilly
Journal, Cancer stem cells: microRNA-873 inhibits self-renewal and proliferation of pancreatic cancer stem cells through pleckstrin-2-dependent PI3K/AKT pathway. (Pubmed Central) - Apr 1, 2022 Then to further investigate specific role of miR-873, the pancreatic cancer stem cells were treated with miR-873 mimic, PLEK2, small interfering RNA against PLEK2, LY294002 (inhibitor of phosphatidylinositol 3-kinase/protein kinase B [PI3K/AKT] pathway) to detect the relative gene expression as well as their effects on cell self-renewal, proliferation and apoptosis...Overall, miR-873 can suppress the self-renewal and proliferation of pancreatic cancer stem cells by blocking PLEK2-dependent PI3K/AKT pathway. Hence, this study contributes to understanding the role of miR-873 in pancreatic cancer stem cells and its underlying molecular mechanisms to aid in the development of effective pancreatic cancer therapeutics.
- |||||||||| Journal: G protein-coupled receptor kinase 2 is essential to enable vasoconstrictor-mediated arterial smooth muscle proliferation. (Pubmed Central) - Apr 1, 2022
These data suggest GRK2 expression is essential to facilitate vasoconstrictor-driven VSMC proliferation through its ability to promote efficient prolonged PI3K-Akt signalling, and thus relieve the GSK3-mediated block on cell cycling. Considering VSMC GRK2 expression increases early in the development of hypertension, this highlights the potential for GRK2 to promote VSMC growth and exacerbate hypertensive pathophysiological vascular remodelling.
- |||||||||| AZD8154 / AstraZeneca
Clinical, Journal: Diurnal variation in DLCO and non-standardized study procedures may cause a false positive safety signal in clinical trials. (Pubmed Central) - Apr 1, 2022 Diffusing capacity for carbon monoxide (DLCO) was measured in a phase I single ascending dose study after inhalation of AZD8154 or placebo in healthy participants at baseline (DLCO) and follow-up (DLCO) 6 days after dosing...The observed reduction in DLCO was confirmed as a false positive finding after alignment of DLCO timings. As a consequence, when DLCO is used in clinical studies, measurements should be strictly standardized in relation to time of the day.
- |||||||||| Review, Journal, IO biomarker: Current advances and trends in KRAS targeted therapies for colorectal cancer. (Pubmed Central) - Mar 31, 2022
Nevertheless, continued assessment of these targeted cancer therapies will eventually allow colorectal cancer patients to be treated using a personalized medicine approach. In this review, the most recent scientific approaches and clinical trials targeting KRAS mutations directly or indirectly for the management of colorectal cancer are discussed.
- |||||||||| inavolisib (GDC-0077) / Roche
Clinical, Journal: RTK-dependent inducible degradation of mutant PI3Kα drives GDC-0077 (Inavolisib) efficacy. (Pubmed Central) - Mar 31, 2022 Both are more effective than other PI3K inhibitors at maintaining prolonged pathway suppression. This study establishes a new strategy for identifying inhibitors that specifically target mutant tumors by selective degradation of the mutant oncoprotein and provide a strong rationale for pursuing PI3Kα degraders in patients with HER2-positive breast cancer.
- |||||||||| Preclinical, Journal: SPRR3, a novel miR-338-3p target, regulates the malignant progression of clear cell renal cell carcinoma in vitro via the PI3K/Akt signaling pathway. (Pubmed Central) - Mar 31, 2022
The results indicated the following: i) SPRR3 was a risk factor for the survival of patients with ccRCC, and was upregulated in ccRCC cell lines; ii) SPRR3 promoted the proliferation, migration and invasion of ccRCC cells; iii) SPRR3 regulated the tumor phenotypes of ccRCC cells via the PI3K/Akt pathway; iv) miR-338-3p directly targeted SPRR3 mRNA and negatively regulated SPRR3 expression; and v) miR-338-3p inhibited the PI3K/Akt pathway and the tumor phenotypes of ccRCC cells by downregulating SPRR3. In conclusion, SPRR3, as a novel target of miR-338-3p, regulated the proliferation, migration and invasion of ccRCC cells via the PI3K/Akt pathway; this finding not only enriches our understanding of the mechanism underlying ccRCC development, but also demonstrates a potential novel therapeutic target for this disease.
- |||||||||| Journal: The PIK3CA H1047R Mutation Confers Resistance to BRAF and MEK Inhibitors in A375 Melanoma Cells through the Cross-Activation of MAPK and PI3K-Akt Pathways. (Pubmed Central) - Mar 27, 2022
In this study, three different A375 cell melanoma models either overexpressing or not expressing the wild-type or mutated form of the PhosphatidylInositol-4,5-bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) gene were used to clarify the therapeutic response of melanoma to BRAF, Mitogen-Activated Protein Kinase Kinase 1 (MEK), and PI3K inhibitors in the presence of the PIK3CA H1047R mutation. Our data strongly support the notion that the crosstalk between the MAPK and PI3K-Akt pathways is one of the main mechanisms associated with melanoma development and progression and that the combination of MAPK and PI3K inhibitors may sensitize melanoma cells to therapy.
- |||||||||| Journal: M2 macrophages, but not M1 macrophages, support megakaryopoiesis by upregulating PI3K-AKT pathway activity. (Pubmed Central) - Mar 26, 2022
Furthermore, our preliminary data indicated that TGF-β released by M2 MФs may facilitate megakaryopoiesis through upregulation of the JAK2/STAT5 and MAPK/ERK pathways in MKs. Taken together, our data reveal that M1 and M2 MФs have opposing effects on MKs in a PI3K-AKT pathway-dependent manner, which may lead to new insights into the pathogenesis of thrombocytopenia and provide a potential therapeutic strategy to promote megakaryopoiesis.
- |||||||||| cisplatin / Generic mfg.
Journal: MAP4K4 mediates the SOX6-induced autophagy and reduces the chemosensitivity of cervical cancer. (Pubmed Central) - Mar 26, 2022 Moreover, cisplatin itself could promote the expression of endogenous SOX6 and subsequently the MAP4K4-mediated autophagy in cervical cancer cells, which might in turn reduce the sensitivity of these cells to cisplatin treatment. These findings uncovered the underlying mechanism and potential significance of SOX6-induced autophagy, and shed new light on the usage of MAP4K4 inhibitor or autophagy-specific inhibitor for sensitizing cervical cancer cells to the platinum-based chemotherapy.
- |||||||||| metformin / Generic mfg.
Preclinical, Journal, IO biomarker: Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo. (Pubmed Central) - Mar 26, 2022 In addition, a PI3K inhibitor (LY-294002) and a Nrf2 inhibitor (ML385) observably attenuated the protective effects of MET on MGO-induced apoptosis and ROS generation by inhibiting the Nrf2/HO-1 pathways, while a ROS scavenger (NAC) and a permeability transition pores inhibitor (CsA) completely reversed these effects. Collectively, these findings broaden our understanding of the mechanism by which MET regulates apoptosis induced by MGO under oxidative stress conditions, with important implications regarding the potential application of MET for the treatment of diabetic vascular complications.
- |||||||||| 5-fluorouracil / Generic mfg., metformin / Generic mfg.
Preclinical, Journal, IO biomarker: In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network. (Pubmed Central) - Mar 26, 2022 In conclusion, metformin monotherapy was superior to VD, whereas the 5-FU/Met protocol showed better anticancer effects relative to the other dual therapies. However, the 5-FU/VD/Met approach displayed the best in vivo and in vitro tumoricidal effects related to cell cycle arrest and apoptosis, justifiably by enhanced modulations of the PI3K/PTEN/Akt/mTOR pathway.
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