Human Olfactory Lobe Tissue Lysate
- Known as:
- Human Olfactory Lobe Tissue Lysate
- Catalog number:
- 30r-ao004
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- Human Olfactory Lobe Tissue Lysate
Related genes to: Human Olfactory Lobe Tissue Lysate
- Gene:
- AKT1S1 NIH gene
- Name:
- AKT1 substrate 1
- Previous symbol:
- -
- Synonyms:
- PRAS40, MGC2865, Lobe
- Chromosome:
- 19q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-04
- Date modifiied:
- 2016-04-26
Related products to: Human Olfactory Lobe Tissue Lysate
Related articles to: Human Olfactory Lobe Tissue Lysate
- Serine/threonine-proline (S/T-P) phosphorylation is a fundamental mechanism maintaining cellular homeostasis. Although glycogen synthase kinase 3β (GSK3β) is a key regulator in ischemic stroke, the contribution of its proline-directed kinase activity to cellular dysfunction and disease progression remains unclear. Here, we developed Nb.29E9, a nanobody that selectively targets the proline-directed kinase domain of GSK3β. Under ischemic conditions, Nb.29E9 inhibited S/T-P phosphorylation of key substrates, including RNA-binding motif protein 38 (RBM38), HIF1α, and p53, thereby enhancing neuronal and microglial viability while reducing oxidative stress and neuroinflammation. Phosphoproteomic analysis revealed broad reprogramming of S/T-P phosphorylation networks. In mice after ischemic injury, Nb.29E9 delivered via a brain-penetrant, MMP-9-responsive nanoparticle reduced infarct volume, restored neurovascular integrity, and improved motor function. Mechanistically, Nb.29E9 corrected pathological hyperphosphorylation of SMAD2/3-Thr8 (TGFβ signaling), calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)-Ser495 (AMPK pathway), and AKT1 substrate 1 (AKT1S1)-Ser183 (mTORC1 regulation). These findings demonstrate that GSK3β's intrinsic proline-directed kinase activity drives ischemic neurodegeneration, establishing its pathogenic role in vivo. - Source: PubMed
Publication date: 2026/06/09
Li LanLi MuyangSun LeiYang YingWu YuanshunYin ZiyiWang AnniZhou PeiyangLuo ShaoxiangChen JianQin JunAi ZhibingYuan ZilongDong ZhiqiangZhang Min - BACKGROUND: Pressure overload first leads to compensated hypertrophy and secondary to heart failure. m6A-RNA methylation is a fast process for the adaptation of cell composition. m6A-RNA-methylation is regulated by the demethylase, fat mass and obesity-associated protein (FTO), and FTO protein levels are diminished in heart failure. Cardiomyocyte-specific FTO-transgenic/knockout-mice have shown the relevance of FTO in pressure overload remodeling. However, its functional downstream regulatory mechanisms are still unclear. In this study, we discover the harmful signaling pathways that are triggered by m6A imbalance and FTO loss, which eventually lead to adverse cardiac remodeling and heart failure. METHODS: FTOcKO animals were generated by crossing FTOfl/fl mice with α-MHC Cre mice using Cre-lox system. Control and the FTOcKO animals groups were subjected to TAC (transverse aortic constriction) surgery. Echocardiography was performed 1-week post-TAC surgery. MeRIP (m6A RNA immunoprecipitation) sequencing was performed from the heart tissues of mice after one week TAC surgery. Additionally, the mechanistical interrelation between the signaling pathways during FTO loss and adverse cardiac remodeling were investigated in human iPS-CMs (hiPS-CMs). RESULTS: One week post-TAC surgery, FTOcKO mice showed impaired cardiac function (EF: CreC TAC (45%) vs. FTOcKO TAC (25%), p < 0.0001) and increased LVID (CreC TAC(3.9 mm) vs. FTOcKO TAC (4.8 mm), p < 0.0001), indicating a lack of adaption to pressure overload. Knockdown of FTO in hiPS-cardiomyocytes also reduced endothelin-induced hypertrophic response. MeRIP-seq data of FTOcKO mice showed that the differentially hypermethylated transcripts were associated with cardiac apoptosis inhibition (CDK1, CFLAR), mTORC1 signaling pathway (AKT1S1) and autophagy regulation (TFEB). mTORC1 was identified as a central player of dysregulation with hyperactivation of its canonical substrates phospho-S6K1 (Thr 389) and phospho-S6 (ser235/236) ex-vivo (FTOcKO) and in-vitro (FTO-KD-hiPS-CMs). Moreover, FTO-deficient cardiomyocytes cause autophagic flux impairment and defective autophagy. The effect of atrophy and induced apoptosis upon FTO-m6A imbalance could be rescued by pharmacological inhibiton of the mTORC1-S6K1 pathway. CONCLUSIONS: Downregulation of FTO leads to mTORC1-S6K1 hyperactivation that shift the compensative hypertrophic response to atrophy and apoptosis leading to progressive heart failure. These findings might pave the way for the development of novel therapeutic targets for the early phases of heart failure treatments. - Source: PubMed
Publication date: 2025/12/02
Annamalai KarthikaDilliker SoniyaBuchholz EricCastro-Hernández RicardoPanyam NikitaPommeranz AlessaWiederhake PascalWery von Limont NellyHempel NinaEbner VerenaSwarnkar SurabhiMohamed Belal AStreckfuss-Bömeke KatrinSteffens SabineHerzig StephanEbert AntjeFischer AndreToischer Karl - Immune checkpoint blockade (ICB) has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), yet primary resistance remains a significant clinical challenge. Recent evidence implicates PRAS40 (AKT1S1) in regulating cellular survival and immune responses, but its role in immunotherapy resistance is not fully understood. - Source: PubMed
Publication date: 2025/10/10
Mao NingHe CuiKuang JiaWang ChunguangYang Zhao - This study aimed to investigate the underlying mechanisms by which dandelion extract inhibits the proliferation of breast cancer MDA-MB-231 cells. Dandelion root and leaf extracts were prepared using a heat reflux method and subjected to solvent gradient extraction to obtain fractions with different polarities. MTT assays revealed that the ethyl acetate fraction exhibited the strongest inhibitory effect on cell proliferation. LC-MS analysis identified 12 potential active compounds, including sesquiterpenes such as Isoalantolactone and Artemisinin, which showed significantly lower toxicity toward normal mammary epithelial MCF-10A cells compared to tumor cells ( < 0.01). Mechanistic studies demonstrated that the extract induced apoptosis in a dose-dependent manner, with an apoptosis rate as high as 85.04%, and significantly arrested the cell cycle at the S and G2/M phases. Label-free quantitative proteomics identified 137 differentially expressed proteins (|FC| > 2, < 0.05). GO enrichment analysis indicated that these proteins were mainly involved in cell cycle regulation and apoptosis. KEGG pathway analysis revealed that the antitumor effects were primarily mediated through the regulation of PI3K-Akt (hsa04151), JAK-STAT (hsa04630), and PPAR (hsa03320) signaling pathways. Moreover, differential proteins such as PI3K, AKT1S1, SIRT6, JAK1, SCD, STAT3, CASP8, STAT2, STAT6, and PAK1 showed strong correlation with the core components of the EA-2 fraction of dandelion. Molecular docking results demonstrated that these active compounds exhibited strong binding affinities with key target proteins such as PI3K and JAK1 (binding energy < -5.0 kcal/mol). This study elucidates the multi-target, multi-pathway synergistic mechanisms by which dandelion extract inhibits breast cancer, providing a theoretical basis for the development of novel antitumor agents. - Source: PubMed
Publication date: 2025/07/22
Mou WeifengZhang PingCui YuYang DoudouZhao GuanjieXu HaijunZhang DandanLiang Yinku - Dogs are the only large mammals, besides humans, that develop spontaneous prostate cancer, which has a poor prognosis and limited treatment efficacy. Considering the central role of mammalian target of rapamycin (mTOR) in carcinogenesis, the use of rapamycin, an mTOR inhibitor, has attracted considerable attention. In this study, we performed gene expression microarray analyses of normal canine prostate and prostate carcinoma cells. Among the 6,270 differentially expressed genes revealed in the transcriptome, 3,242 were upregulated and 3,028 were downregulated, and were related to phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway activation, as confirmed by enrichment analysis. Among the genes involved in this pathway, we found increased expression levels of FKBP1A, FKBP1B, AKT1S1, PDK2, PIP5K1 and PIP5KL1 in canine prostate cancer cells compared with normal prostate cells. We also treated two canine prostate cancer cell lines (PC1 and PC2) with rapamycin in vitro (6, 10 and 12 μM) for 24 h and observed a dose-dependent decrease in cell viability. Our results indicate that rapamycin significantly increased AKT transcript levels in both cell lines, indicating resistance to treatment. However, mTOR and 4E-BP1 expression were downregulated after rapamycin treatment. We suggest that mTOR inhibition is a potential treatment of choice for canine prostate cancer, which may guide and contribute to future prostate carcinoma clinical trials. However, the acquisition of resistance to treatment remains a challenge, and precision medicine may help overcome this problem. - Source: PubMed
Publication date: 2025/05/05
Kobayashi Priscila ELainetti Patrícia FLeis-Filho Antonio FDelella Flávia KVicente Igor S TFonseca-Alves Carlos ELaufer-Amorim Renée