Rapamycin inhibits B-cell activating factor (BAFF)-stimulated cell proliferation and survival by suppressing Ca2+-CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells

Zeng, Qingyu; Zhou, Zhihan; Qin, Shanshan; Yao, Yajie; Qin, Jiamin; Zhang, Hai; Zhang, Ruijie; Xu, Chong; Zhang, Shuangquan; Huang, Shile; Chen, Long

doi:10.1016/j.ceca.2020.102171

Cited by 20 publications

(8 citation statements)

References 62 publications

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“…After PTEN expression was inhibited, axon regeneration was promoted in corticospinal neurons by upregulation of mTOR activity. [ 43,44 ] Our in vitro results demonstrated that the GMP hydrogel significantly increased neuron and oligodendrocyte differentiation but reduced astrocyte differentiation in comparison with control and GM groups. Compared to the GMPE group, GMP yielded better performance in the Tuj‐1 level during the in vitro study.…”

Section: Discussionmentioning

confidence: 82%

Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth

et al. 2022

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Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell‐derived exosomes (BMSC‐exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue‐like electroconductive hydrogels loaded with BMSC‐exosomes are developed for the synergistic treatment of SCI. These exosomes‐loaded electroconductive hydrogels modulate microglial M2 polarization via the NF‐κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68‐positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC‐exosomes is a promising therapeutic strategy for SCI repair.

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Section: Discussionmentioning

confidence: 82%

Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth

et al. 2022

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“…Cells were then imaged by inverted fluorescence microscope (Lecia, Germany). Intracellular Ca 2+ fluorescence value was detected as previously study described [ 21 ], briefly, cells stained with Fluo-4 AM in 6-well plates were digested with 0.25% trypsin without EDTA and washed with PBS, followed by dilution to 2 × 10 6 cells/ml with PBS. Finally, cell suspension was added into a black clear bottom 96-well plate (150 μl/well), and the fluorescence value was measured by multifunctional microplate reader under the condition of 488 nm excitation wavelength and 520 nm emission wavelength.…”

Section: Methodsmentioning

confidence: 99%

L-theanine prevents progression of nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway

Jiang

Liu

et al. 2022

Nutr Metab (Lond)

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Background L-theanine, a non-protein amino acid was found principally in the green tea, has been previously shown to exhibit potent anti-obesity property and hepatoprotective effect. Herein, we investigated the effects of L-theanine on alleviating nonalcoholic hepatic steatosis in vitro and in vivo, and explored the underlying molecular mechanism. Methods In vitro, HepG2 and AML12 cells were treated with 500 μM oleic acid (OA) or treated with OA accompanied by L-theanine. In vivo, C57BL/6J mice were fed with normal control diet (NCD), high‐fat diet (HFD), or HFD along with L-theanine for 16 weeks. The levels of triglycerides (TG), accumulation of lipid droplets and the expression of genes related to hepatocyte lipid metabolic pathways were detected in vitro and in vivo. Results Our data indicated that, in vivo, L-theanine significantly reduced body weight, hepatic steatosis, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), TG and LDL cholesterol (LDL-C) in HFD-induced nonalcoholic fatty liver disease (NAFLD) mice. In vitro, L-theanine also significantly alleviated OA induced hepatocytes steatosis. Mechanic studies showed that L-theanine significantly inhibited the nucleus translocation of sterol regulatory element binding protein 1c (SREBP-1c) through AMPK-mTOR signaling pathway, thereby contributing to the reduction of fatty acid synthesis. We also identified that L-theanine enhanced fatty acid β-oxidation by increasing the expression of peroxisome proliferator–activated receptor α (PPARα) and carnitine palmitoyltransferase-1 A (CPT1A) through AMP-activated protein kinase (AMPK). Furthermore, our study indicated that L-theanine can active AMPK through its upstream kinase Calmodulin-dependent protein kinase kinase-β (CaMKKβ). Conclusions Taken together, our findings suggested that L-theanine alleviates nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway.

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“…Preclinical trials were conducted to study and confirm the cell inhibiting effects of rapamycin on glioblastoma and medulloblastoma xenografts (Kuger et al, 2013). However, compared to PTEN-positive tumors, the PTEN negative tumors are more sensitive to the inhibiting effects of rapamycin (Zeng et al, 2020). Clinical study results revealed that the mTOR and PI3K inhibitors were the candidate drugs which could be used to treat solid tumors in mice (LoRusso, 2016).…”

Section: Phosphatase Tensin Homolog Gene: Mutationmentioning

confidence: 99%

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Wei

et al. 2022

Front. Mol. Neurosci.

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As is known to all, glioma, a global difficult problem, has a high malignant degree, high recurrence rate and poor prognosis. We analyzed and summarized signal pathway of the Hippo/YAP, PI3K/AKT/mTOR, miRNA, WNT/β-catenin, Notch, Hedgehog, TGF-β, TCS/mTORC1 signal pathway, JAK/STAT signal pathway, MAPK signaling pathway, the relationship between BBB and signal pathways and the mechanism of key enzymes in glioma. It is concluded that Yap1 inhibitor may become an effective target for the treatment of glioma in the near future through efforts of generation after generation. Inhibiting PI3K/Akt/mTOR, Shh, Wnt/β-Catenin, and HIF-1α can reduce the migration ability and drug resistance of tumor cells to improve the prognosis of glioma. The analysis shows that Notch1 and Sox2 have a positive feedback regulation mechanism, and Notch4 predicts the malignant degree of glioma. In this way, notch cannot only be treated for glioma stem cells in clinic, but also be used as an evaluation index to evaluate the prognosis, and provide an exploratory attempt for the direction of glioma treatment. MiRNA plays an important role in diagnosis, and in the treatment of glioma, VPS25, KCNQ1OT1, KB-1460A1.5, and CKAP4 are promising prognostic indicators and a potential therapeutic targets for glioma, meanwhile, Rheb is also a potent activator of Signaling cross-talk etc. It is believed that these studies will help us to have a deeper understanding of glioma, so that we will find new and better treatment schemes to gradually conquer the problem of glioma.

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Rapamycin inhibits B-cell activating factor (BAFF)-stimulated cell proliferation and survival by suppressing Ca2+-CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells

Cited by 20 publications

References 62 publications

Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth

Exosomes‐Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth

L-theanine prevents progression of nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

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