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- | Journal: Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway. (Pubmed Central) - Apr 12, 2022
Furthermore, there were no significant difference between the HI and HPNU groups in serum LDH, CK-MB, cTnI, TNF-α and IL-6 levels, infarct size, myocardial p-Akt/Akt and eNOS/GAPDH ratios. In conclusion, hypercholesterolemia could aggravate myocardial ischemia/reperfusion injury, attenuate cardioprotection of ischemic preconditioning and eliminate cardioprotection from α7nAChR agonist postconditioning by enhancing inflammation and inhibiting PI3K/Akt/eNOS pathway.
- || Review, Journal: Cardiac Toxicity From Adjuvant Targeting Treatment for Breast Cancer Post-Surgery. (Pubmed Central) - Apr 12, 2022
The cardiac adverse events of traditional endocrine therapy, radiotherapy, and chemotherapy for breast cancer have been widely detected in clinic; however, the targeting therapy agents have been paid more attention with the extension of application. This review will summarize the cardiac toxicity of various adjuvant therapies for breast cancer, especially for targeting drug therapy.
- LY294002 / Eli Lilly
Bladder oxidative stress and ERK signaling contribute to bladder pain mediated by macrophage migration inhibitory factor and High Mobility Group Box 1 (Room 228) - Apr 10, 2022 - Abstract #AUA2022AUA_1452;
Downstream of HMGB1, ROS production and ERK1/2 activation at the level of the bladder mediate bladder pain. Further dissecting HMGB1 downstream signaling pathway may lead to novel potential therapeutic strategies to treat non-inflammatory bladder pain.
- | gedatolisib (PF-05212384) / Celcuity
Preclinical, Journal: The PI3K/mTOR inhibitor Gedatolisib eliminates dormant breast cancer cells in organotypic culture, but fails to prevent metastasis in preclinical settings. (Pubmed Central) - Apr 9, 2022
These data suggest that PI3K is not the node downstream of integrin-β1 that confers chemotherapeutic resistance to DTCs. More broadly, they cast doubt on the strategy to target PI3K in order to eliminate DTCs and prevent breast cancer metastasis.
- || Piqray (alpelisib) / Novartis
Clinical, Journal: Recent clinical advances in PI3K inhibitors on colorectal cancer. (Pubmed Central) - Apr 9, 2022
Inhibitors targeting PI3K, a key protein in the PI3K/Akt/mTOR signaling pathway, have a positive effect on the treatment of colorectal cancer. Based on the role of PI3K/Akt/mTOR in the occurrence and development of colorectal cancer and its clinical application, this article reviews the PI3K inhibitors that have been on the market or are in clinical trials.
- | LY294002 / Eli Lilly
Journal: Ribophorin II promotes the epithelial-mesenchymal transition and aerobic glycolysis of laryngeal squamous cell carcinoma via regulating reactive oxygen species-mediated Phosphatidylinositol-3-Kinase/Protein Kinase B activation. (Pubmed Central) - Apr 9, 2022
In xenografted mice, silencing RPN2 expression reduced tumor growth, ROS production, and levels of Ki-67, Vimentin, LDHA, and p-Akt/Akt, but enhanced E-cadherin expression. In conclusion, our data suggested that RPN2 promoted the proliferation, migration, EMT, and glycolysis of LSCC via modulating ROS-mediated PI3K/Akt activation.
- | niclosamide / Generic mfg.
Journal: Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway. (Pubmed Central) - Apr 9, 2022
The above findings demonstrated the potential antifibrotic effect of NEN mediated via modulation of the PI3K-mTORC1 and autophagy pathways. These data provide strong evidence for a therapeutic role for NEN in IPF.
- | Journal: Dysregulated PI3K Signaling in B Cells of CVID Patients. (Pubmed Central) - Apr 9, 2022
In contrast to CVID, increased basal activity of PI3K in patients with a gain-of-function mutation in PIK3CD and activated PI3K delta syndrome (APDS) did not result in impaired BCR-induced AKT-mTOR-S6 phosphorylation, highlighting that signaling defects in B cells in CVID and APDS patients are fundamentally different and that assessing responses to BCR stimulation is an appropriate confirmative diagnostic test for APDS. The active PI3K signaling in vivo may render autoreactive T-betCD21 B cells in CVID at the same time to be more sensitive to mTOR or PI3K inhibition.
- | Journal, Combination therapy: ACAGT-007a, an ERK MAPK Signaling Modulator, in Combination with AKT Signaling Inhibition Induces Apoptosis in KRAS Mutant Pancreatic Cancer T3M4 and MIA-Pa-Ca-2 Cells. (Pubmed Central) - Apr 9, 2022
Consistently, a PI3K inhibitor, Wortmannin, abolished AKT phosphorylation and enhanced GT-7-mediated apoptosis in T3M4 and MIA-Pa-Ca-2, but not in PANC-1, which showed residual AKT phosphorylation. This is the first report that ERK stimulation alone or in combination with AKT signaling inhibition can effectively induce apoptosis in PDAC and provides a rationale for a novel concurrent targeting of the PI3K/AKT and ERK pathways.
- | Journal: Cyclin D1 mediated by the nuclear translocation of nuclear factor kappa B exerts an oncogenic role in lung cancer. (Pubmed Central) - Apr 9, 2022
Inhibition of PI3K/AKT pathway activity or suppression of NF-κB translocation in cells with high CCND1 expression was found to significantly reduce the activity of lung cancer cells in vitro and in vivo. Our data revealed that NF-κB/CCND1/PI3K/AKT axis could act as a prospective diagnostic biomarker and a therapeutic option for lung cancer.
- | trimetazidine / Generic mfg.
Journal: Trimetazidine mitigates high glucose-induced retinal endothelial dysfunction by inhibiting PI3K/Akt/mTOR pathway-mediated autophagy. (Pubmed Central) - Apr 9, 2022
Moreover, the autophagy agonist rapamycin (RAPA) was also testified to reverse the inhibitory effects of TMZ on the proliferation, migration, and angiogenesis of HG-induced HRECs. In summary, TMZ inhibited excessive autophagy by activating PI3K/Akt/mTOR pathway, thereby improving retinal endothelial dysfunction induced by HG.
- | cisplatin / Generic mfg.
Preclinical, Journal, IO biomarker: Fuzheng Jiedu Decoction Induces Apoptosis and Enhances Cisplatin Efficacy in Ovarian Cancer Cells In Vitro and In Vivo through Inhibiting the PI3K/AKT/mTOR/NF-κB Signaling Pathway. (Pubmed Central) - Apr 9, 2022
This study indicated that FJD could improve the efficacy of cisplatin by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. It is suggested that FJD may be a valuable adjuvant drug for the treatment of OC.
- | Journal: Targeting SHP2 phosphatase in breast cancer overcomes RTK-mediated resistance to PI3K inhibitors. (Pubmed Central) - Apr 9, 2022
Our results highlight the importance of SHP2 as a player in resistance to PI3K inhibitors. Combination treatment with PI3K and SHP2 inhibitors could pave the way for significant improvements in therapies for breast cancer.
- || Review, Journal: PI3K/Akt/mTOR Signaling Pathway: Role in Esophageal Squamous Cell Carcinoma, Regulatory Mechanisms and Opportunities for Targeted Therapy. (Pubmed Central) - Apr 9, 2022
This review mainly introduces the general situation of ESCC, the composition and function of PI3K/Akt/mTOR pathway, and regulatory factors that interact with PI3K/Akt/mTOR signaling pathway. Meanwhile, mutations and inhibitors of PI3K/Akt/mTOR pathway in ESCC are also elucidated.
- | Nexavar (sorafenib) / Bayer, Amgen
Journal: FNDC5 Causes Resistance to Sorafenib by Activating the PI3K/Akt/Nrf2 Pathway in Hepatocellular Carcinoma Cells. (Pubmed Central) - Apr 9, 2022
In addition, FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib.
- | Preclinical, Journal, IO biomarker: Saikosaponin-A induces apoptosis of cervical cancer through mitochondria- and endoplasmic reticulum stress-dependent pathway in vitro and in vivo: involvement of PI3K/AKT signaling pathway. (Pubmed Central) - Apr 8, 2022
These findings at least to a certain extent suggested that saikosaponin-A triggered apoptosis through both mitochondrial pathway and ER stress pathway and inhibiting PI3K/Akt signaling, thereby contributing to against cervical cancer. This work provides a new understanding of saikosaponin-A on therapeutic application in treatment of cancer, which has the potential to be a promising candidate therapeutic agent for cervical cancer patients.
- || buparlisib (AN2025) / Novartis, Adlai Nortye
Clinical, P1 data, Journal, IO biomarker: Phase I/Ib study of the efficacy and safety of buparlisib and ibrutinib therapy in MCL, FL, and DLBCL with serial cell-free DNA monitoring. (Pubmed Central) - Apr 8, 2022
P1
BTK and pan-PI3K inhibition in mantle cell lymphoma demonstrates a promising efficacy signal. Addition of BCL2 inhibitors to a BTK and pan-PI3K combination remain suitable for further development in mantle cell lymphoma.
- || Preclinical, Review, Journal, IO biomarker: Vibrio harveyi infections induce production of proinflammatory cytokines in murine peritoneal macrophages via activation of p38 MAPK and NF-κB pathways, but reversed by PI3K/AKT pathways. (Pubmed Central) - Apr 8, 2022
The secretion of IL-1β, IL-6, IL-12, and TNF-α were considerably reduced when the p38 MAPK and NF-κB signaling pathways were blocked, whereas blocking of AKT significantly increased the expression of IL-1β, IL-6, IL-12, and TNF-α. These findings indicate that V. harveyi infection induces inflammatory responses in murine PMs via activation of p38 MAPK and NF-κB pathways, which are partly mediated by TLR2, but are inhibited by PI3K/AKT pathways.
- | LY294002 / Eli Lilly
Journal: The neuroprotective effects of Insulin-Like Growth Factor 1 via the Hippo/YAP signaling pathway are mediated by the PI3K/AKT cascade following cerebral ischemia/reperfusion injury. (Pubmed Central) - Apr 8, 2022
LY294002 treatment not only downregulated PI3K and p-AKT, but YAP/TAZ as well, leading to aggravation of neurological dysfunction and worsening of brain damage. Our findings indicate that the neuroprotective effects of IGF-1 are, at least in part mediated by upregulation of YAP/TAZ via activation of the PI3K/AKT cascade following cerebral ischemic stroke.
- | Venclexta (venetoclax) / Roche, AbbVie
Journal: Recognizing Unmet Need in the Era of Targeted Therapy for CLL/SLL: "What's Past is Prologue" (Shakespeare). (Pubmed Central) - Apr 8, 2022
We also critically review the literature for PI3K inhibitors and chemoimmunotherapy and lack of data to support their utility following BTK inhibitors and venetoclax. Finally, we suggest opportunities to ensure the continued innovation for patients with CLL.
- | Journal: KIAA0101 knockdown inhibits glioma progression and glycolysis by inactivating the PI3K/AKT/mTOR pathway. (Pubmed Central) - Apr 8, 2022
Mechanistically, KIAA0101 knockdown inhibited the PI3K/AKT/mTOR pathway. In conclusion, KIAA0101 silencing inhibited glioma progression and glycolysis by inactivating the PI3K/AKT/mTOR pathway.
- | Journal: Downregulation of FAPP2 gene induces cell autophagy and inhibits PI3K/AKT/mTOR pathway in T-cell acute lymphoblastic leukemia. (Pubmed Central) - Apr 8, 2022
In summary, our results show that decreased expression of FAPP2 inhibited cell proliferation, resulted in the sub-G1 phase accumulation of T-ALL cells, and enhanced autophagy of T-ALL cells, likely mediated by PI(4)P, PI(3,4,5)P, and PI3K/AKT/mTOR pathway. Our results provide a new insight into the pathogenesis and development of potential targeted therapy of T-ALL.
- | Journal: Long non-coding RNA MALAT1 modulates myocardial ischemia-reperfusion injury though the PI3K/Akt/eNOS pathway by sponging miRNA-133a-3p to target IGF1R expression. (Pubmed Central) - Apr 8, 2022
MALAT1 regulates miR-133a-3p /IGF1R axis. These results show light on the underlying mechanisms of MIRI and provide potential therapeutic targets for MIRI.
- || Verzenio (abemaciclib) / Eli Lilly
Biomarker, Review, Journal, Tumor Mutational Burden, BRCA Biomarker, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker: Updates on breast biomarkers. (Pubmed Central) - Apr 8, 2022
Importantly, in the metastatic setting, numerous predictive biomarkers have emerged, including recommendations for germline BRCA mutation testing for all metastatic patients (to determine if PARP inhibitor therapy is an option) and other ER-/HER2-dependent biomarkers such as PD-L1 (for potential immunotherapy in triple negative patients) and PIK3CA mutation status (for potential PI3K inhibitor therapy in ER-positive metastatic patients). Other less common biomarkers of targeted therapy options (e.g., MSI/MMR, TMB, NTRK) as well as comprehensive genomic profiling to identify uncommon targets are also available in the metastatic setting to determine additional treatment options.
- | LY294002 / Eli Lilly
Journal: Exogenous pancreatic kininogenase protects against tacrolimus-induced renal injury by inhibiting PI3K/AKT signaling: The role of bradykinin receptors. (Pubmed Central) - Apr 8, 2022
Other less common biomarkers of targeted therapy options (e.g., MSI/MMR, TMB, NTRK) as well as comprehensive genomic profiling to identify uncommon targets are also available in the metastatic setting to determine additional treatment options. These findings indicate that PK treatment protects against chronic TAC nephrotoxicity via inhibition of PI3K/AKT signaling.
- | LY294002 / Eli Lilly
Journal, IO biomarker: Cinnamaldehyde Downregulation of Sept9 Inhibits Glioma Progression through Suppressing Hif-1α via the Pi3k/Akt Signaling Pathway. (Pubmed Central) - Apr 8, 2022
Pi3k inhibitor (LY294002) was used for interfering with cells, and the results found CA to demonstrate a similar effect...It is suggested that the mechanism of Sept9 under hypoxia regulation can be realized through the Pi3k/Akt pathway. This study proves for the first time that CA is an effective drug for inhibiting the proliferation of glioma through Sept9 and reveals Sept9 to be related to the Pi3k/Akt pathway in terms of tumor microenvironment, providing a molecular basis for the further study of CA in glioma treatment.
- | esomeprazole / Generic mfg.
Journal: PI3K inhibitor 3-MA promotes the antiproliferative activity of esomeprazole in gastric cancer cells by downregulating EGFR via the PI3K/FOXO3a pathway. (Pubmed Central) - Apr 8, 2022
Furthermore, pretreatment with the EGFR inhibitor AG1478 enhanced the antiproliferative activity of ESO in gastric cancer cells. In conclusion, our results suggested that the PI3K inhibitor 3-MA promotes the antiproliferative activity of ESO in gastric cancer cells by synergistically downregulating EGFR via the PI3K/FOXO3a pathway.
- | LY294002 / Eli Lilly
Journal: Cinnamaldehyde attenuates kidney senescence and injury through PI3K/Akt pathway-mediated autophagy via downregulating miR-155. (Pubmed Central) - Apr 8, 2022
LY294002 potentiated D-gal-induced effects, and reversed cinnamaldehyde- and miR-155 inhibitor-caused impacts on the PI3K/Akt pathway and LC3-II/LC3-I level in D-gal-induced cells. Cinnamaldehyde attenuates kidney senescence and injury through PI3K/Akt pathway-mediated autophagy via downregulating miR-155.
- | metformin / Generic mfg.
Journal: Metformin Promotes Differentiation and Attenuates HO-Induced Oxidative Damage of Osteoblasts via the PI3K/AKT/Nrf2/HO-1 Pathway. (Pubmed Central) - Apr 8, 2022
We also revealed that metformin could improve bone mass and oxidative level of OVX mice. In conclusion, our study revealed that metformin promoted osteogenic differentiation and HO-induced oxidative damage of osteoblasts via the PI3K/AKT/Nrf2/HO-1 pathway.
- | Journal: Taxifolin as a Major Bioactive Compound in the Vasorelaxant Effect of Different Pigmented Rice Bran Extracts. (Pubmed Central) - Apr 8, 2022
Additionally, taxifolin exhibited, at least in part, similar vasoprotective effects of RRBE. Therefore, we propose that RRBE may serve as natural sources of functional phytochemicals that improve cardiovascular diseases associated with disturbed NO production and endothelial dysfunction.
- PIK3IP1/TrIP Immune Regulation on CD8+ T Cells Restricts Anti-Tumor Immunity (Exhibit Hall; P964) - Apr 8, 2022 - Abstract #IMMUNOLOGY2022IMMUNOLOGY_1924;
In conclusion, TrIP plays a significant role in the antitumor immune activity of CD8+ T cells. The TrIP KO mice are resistant to tumor challenge and display an increase in TIL T cell infiltrate. These data describes TrIP as an interesting potential target for immunotherapy.
- Zydelig (idelalisib) / Gilead
Class II Phosphatidylinositol-3-kinases Promotes CCR7 Recycling to the Cell Membrane in Human T-Cells (Exhibit Hall; P161) - Apr 8, 2022 - Abstract #IMMUNOLOGY2022IMMUNOLOGY_1068;
To determine the site within the cells where CCR7 was retained following inhibition of only class II PI3K, we used HEK-293 cells transfected with CCR7-eGFP and the trans-Golgi network (TGN) marker, TPST2-mCherry, ± 1μM wortmannin, which is required to inhibit class II PI3K in HEK-293 cells. We found that after receptor internalization with CCL19 and 30 minutes of recycling, CCR7-eGFP remained within the TGN in the presence of wortmannin, in contrast CCR7-eGFP, which recycled to the cell membrane in the absence of wortmannin, demonstrating a role for class II PI3K in CCR7 recycling.
- | Journal: Liquidambar orientalis Mill. gum extract induces autophagy via PI3K/Akt/mTOR signaling pathway in prostate cancer cells. (Pubmed Central) - Apr 7, 2022
The protein levels of p-PI3K, p-Akt and p-mTOR were evaluated by western blot analysis. In the present study, it is shown that the SLG extract containing a considerable amount of ravidomycin derivate induced autophagic cell death in prostate cancer cells via inhibiting the PI3K/Akt/mTOR pathway.
- | LY294002 / Eli Lilly
Preclinical, Journal, IO biomarker: Controlled microwave-assisted reactions: A facile synthesis of polyfunctionally substituted phthalazines as dual EGFR and PI3K inhibitors in CNS SNB-75 cell line. (Pubmed Central) - Apr 7, 2022
It also caused significant lower protein expression levels of pPI3K, AKT, pAKT and Bcl2 and higher protein expression levels of BAX, Casp3 and Casp9 when compared to untreated cells. Phthalazine (5b) may be an effective, convenient and safe anti-cancer agent acting via proapoptotic and dual EGFR and PI3K kinase inhibitory actions in CNS SNB-75 cell line.
- | LY294002 / Eli Lilly
Preclinical, Journal: Gene knockdown of CCR3 reduces eosinophilic inflammation and the Th2 immune response by inhibiting the PI3K/AKT pathway in allergic rhinitis mice. (Pubmed Central) - Apr 7, 2022
Ly294002 treatment also decreased these inflammatory indexes in a concentration-dependent manner and blocked inflammatory signals from CCR3, but it did not affect the high expression of CCR3 in AR mice. Collectively, our results suggest that conditional knockout of the bone marrow CCR3 gene can reduce eosinophilic inflammation and the Th2 immune response, which may be due to inhibition of the PI3K/AKT pathway.
- | valsartan / Generic mfg.
Preclinical, Journal: Yiqi Yangyin Tongluo Recipe(YYTR)alleviates renal injury in diabetic nephropathy rats by inhibiting PI3K/AKT pathway and aquaporin 2 (AQP2) (Pubmed Central) - Apr 7, 2022
Except the blank group, the rats in other groups were fed with high-glucose and high-fat diet and injected with streptozocin to create diabetic nephropathy (DN) rat models...In addition, compared with 4 mg/kg YYTR group, the above indexes in YYTR combined with 740Y-P group were increased. Conclusion YYTR can protect renal function by down-regulating AQP2 protein expression and inhibiting PI3K/AKT signaling pathway activation.
- || Review, Journal: PIK3CA Mutations Drive Therapeutic Resistance in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. (Pubmed Central) - Apr 7, 2022
Here, we review currently available agents targeting PI3K, discuss their potential role in HER2+ breast cancer, and provide an overview of ongoing trials of PI3K inhibitors in HER2+ disease. Additionally, we review the landscape of PIK3CA mutational testing and highlight the gaps in knowledge that could present potential barriers in the effective application of PI3K inhibitors for treatment of HER2+ breast cancer.
- | LY294002 / Eli Lilly, AG1478 / IDT Australia
Journal: PM2.5 Upregulates the Expression of MUC5AC via the EGFR-PI3K Pathway in Human Sinonasal Epithelial Cells. (Pubmed Central) - Apr 6, 2022
This study demonstrates that short-term PM2.5 exposure increases MUC5AC expression in HNECs. Furthermore, this study shows that PM2.5-induced MUC5AC expression is likely mediated through the EGFR-PI3K pathway.
- | Journal: Hypoxia pretreatment improves the therapeutic potential of bone marrow mesenchymal stem cells in hindlimb ischemia via upregulation of NRG-1. (Pubmed Central) - Apr 6, 2022
Furthermore, the PI3K inhibitor and activator reversed the effect of NRG-1 overexpression and knockdown on angiogenesis. We concludes that hypoxia pretreatment of BM-MSCs facilitates angiogenesis and alleviates HI injury via NRG-1/PI3K/AKT pathway.
- | Aliqopa (copanlisib) / Bayer, Imbruvica (ibrutinib) / AbbVie, J&J
Trial completion date, Trial primary completion date: Copanlisib with Ibrutinib for Patients with Recurrent/ Refractory Primary Central Nervous System Lymphoma (PCNSL) (clinicaltrials.gov) - Apr 6, 2022
P1/2, N=45, Recruiting, Sponsor: Memorial Sloan Kettering Cancer Center
We concludes that hypoxia pretreatment of BM-MSCs facilitates angiogenesis and alleviates HI injury via NRG-1/PI3K/AKT pathway. Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024
- | Piqray (alpelisib) / Novartis, Torisel (temsirolimus) / Pfizer
Journal, Tumor Mutational Burden: Multi-site desmoplastic small round cell tumors are genetically related and immune-cold. (Pubmed Central) - Apr 6, 2022
In addition, the low mutation burden was associated with an immune-cold state in DSRCT. Together, these data reveal multiple genomic and immune features of DSRCT and suggest therapeutic opportunities in patients.
- | Journal, IO biomarker: Sodium Danshensu inhibits the progression of lung cancer by regulating PI3K/Akt signaling pathway. (Pubmed Central) - Apr 5, 2022
Our findings also revealed that Sodium Danshensu inhibited PI3K/AKT pathway in A549 and NCI-H1299 cells. In conclusion, our study provided the first evidence that Sodium Danshensu suppressed the malignant biological behaviors of lung cancer cells, indicating that Sodium Danshensu might be a latent candidate for lung cancer therapy.
- | LY294002 / Eli Lilly
Journal: Saikosaponin-D Mitigates Oxidation in SH-SY5Y Cells Stimulated by Glutamate Through Activation of Nrf2 Pathway: Involvement of PI3K. (Pubmed Central) - Apr 5, 2022
Furthermore, addition of LY294002, a selective inhibitor of PI3K (phosphatidylinositol 3 kinase), blocked saikosaponin-D-caused Nrf2 nuclear translocation and reversed the protection of saikosaponin-D against glutamate in SH-SY5Y cells...Taken together, our results indicated that saikosaponin-D enhanced cellular antioxidant capacity through not only intrinsic free radical-scavenging activity but also induction of endogenous antioxidant enzyme activities and HO-1 expression mediated, at least in part, by activating PI3K and subsequently Nrf2 nuclear translocation, thereby protecting the SH-SY5Y cells from glutamate-induced oxidative cytotoxicity. In concert, these data raise the possibility that saikosaponin-D may be an attractive candidate for prevention and treatment of AD and other diseases related to oxidation in the future.
- | Journal: Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway. (Pubmed Central) - Apr 5, 2022
Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy. Video Abstract.
- | glibenclamide / Generic mfg., aripiprazole / Generic mfg., sirolimus / Generic mfg.
Journal: The antipsychotic aripiprazole induces peripheral antinociceptive effects through PI3Kγ/NO/cGMP/K pathway activation. (Pubmed Central) - Apr 5, 2022
The PI3K inhibitor (AS605240), but not rapamycin (mTOR kinase inhibitor), reversed the peripheral antinociceptive effect induced by Aripiprazole...The same was seen using glibenclamide, an ATP-dependent K channel blocker...The injection of cGMP-specific phosphodiesterase type 5 inhibitor zaprinast, potentiated the antinociceptive effect induced by a low dose of aripiprazole. The results provide evidence that aripiprazole induces peripheral antinociceptive effects via PI3K/NO/cGMP/K pathway activation.
- | Preclinical, Journal, IO biomarker: Corilagin induces apoptosis and inhibits HMBG1/PI3K/AKT signaling pathways in a rat model of gastric carcinogenesis induced by methylnitronitrosoguanidine. (Pubmed Central) - Apr 5, 2022
In corillagen treament mRNA protein expression levels of HIF-1α, AKT, PI3K, CT4, CD147 and HMGB1 were drastically lowered transcription factors triggering gastric cancer. In Western blot analysis showed released higher apoptotic marker of caspase-3, -9, Bax while Bcl-2 levels were significantly reduced confirming that corilagin triggers apoptosis in gastric cancer.
- | Preclinical, Journal: Application of Bone Marrow Mesenchymal Stem Cells Effectively Eliminates Endotoxemia to Protect Rat from Acute Liver Failure Induced by Thioacetamide. (Pubmed Central) - Apr 5, 2022
BMSCs can eliminate endotoxemia and reduce mortality in rats with ALF, and the PI3K/AKT/mTOR signal pathway is involved in intestinal differentiation. BMSCs transplantation could be a potential candidate for the treatment of endotoxemia in ALF.
- | TGX-221 / Wuhan University, Pfizer, Zydelig (idelalisib) / Gilead
Journal, IO biomarker: IGF-1 regulates astrocytic phagocytosis and inflammation through the p110α isoform of PI3K in a sex-specific manner. (Pubmed Central) - Apr 5, 2022
AG66 suppressed the IGF-1 effect on cytokine expression and counteracted the IGF-1-produced phagocytosis decrease in male reactive astrocytes. Results suggest that sex-differences in the effect of IGF-1 on the AKT-phosphorylation could be due to a lower expression of the p110α in female and that IGF-1-effects on the inflammatory response and phagocytosis of male reactive astrocytes are mediated by p110α/PI3K subunit.
- | LY294002 / Eli Lilly
Journal: Protective role of wogonin following traumatic brain injury by reducing oxidative stress and apoptosis via the PI3K/Nrf2/HO‑1 pathway. (Pubmed Central) - Apr 5, 2022
In addition, LY294002 partially reversed the regulation of wogonin on NOX, caspase‑3, Bax and Bcl‑2 proteins. Therefore, wogonin exerts antioxidant and anti‑apoptotic properties to prevent hippocampal damage following TBI, which is accomplished through the PI3K/Akt/Nrf2/HO‑1 pathway.
- | lovastatin / Generic mfg.
Journal: Identifying pathways regulating the oncogenic p53 family member ΔNp63 provides therapeutic avenues for squamous cell carcinoma. (Pubmed Central) - Apr 5, 2022
In particular, dual inhibition of the PI3K and mTOR pathways reduced ΔNp63 more effectively than single pathway inhibition, and broad-spectrum histone deacetylase inhibitors showed a time-dependent biphasic response, with high level downregulation at the transcriptional level within 24 h. In addition to furthering our understanding of ΔNp63 regulation in squamous cells, these data identify novel drug combinations that may be useful for p63-based therapy of SCC.