- |||||||||| Journal: Irradiation combined with PD-L1 and autophagy inhibition enhances the antitumor effect of lung cancer via cGAS-STING-mediated T cell activation. (Pubmed Central) - Jul 20, 2022
Notably, the autophagy inhibitors distinctively promoted dsDNA aggregation in the cytoplasm and increased the release of cGAS-STING-regulated IFN-β from irradiated cells, which further activated bystander CD8 T cells to release IFN-γ and contributed to ATAE. These findings revealed a signaling cascade loop that the cytokines released from irradiated tumor recruit CD8 T cells that in turn act on the tumor cells with amplified immune responses in PD-L1-deficient host, indicating a potential sandwich therapy strategy of RT combined with PD-L1 blockage and autophagy inhibition.
- |||||||||| Journal: Induction of Autophagy Promotes Clearance of RHO Aggregates and Protects From Retinal Degeneration. (Pubmed Central) - Jul 20, 2022
This was accompanied with a reduction of endoplasmic reticulum (ER)-stress, robust decrease of photoreceptors' cell death, amelioration in both retinal morphology and function culminating in a better preservation of vision. Our study opens new perspectives for a pulsatile pharmacological induction of autophagy as a mutation-independent therapy paving the way toward a more effective therapeutic strategy to treat these devastating retinal disorders due to an accumulation of intracellular toxic aggregates.
- |||||||||| Lynparza (olaparib) / Merck (MSD), AstraZeneca
Journal, BRCA Biomarker, PARP Biomarker: Proteomic Analysis Identifies p62/SQSTM1 as a Critical Player in PARP Inhibitor Resistance. (Pubmed Central) - Jul 20, 2022 Moreover, p62 protein expression was correlated with better overall survival in estrogen receptor-negative breast cancer. Thus, these findings suggest that PARPi-sensitive TNBC cells hyperactivate autophagy as they develop acquired resistance and that pharmacological stimulation of excessive autophagy could lead to cell death and thus overcome PARPi resistance.
- |||||||||| cisplatin / Generic mfg.
Journal: Pannexin1 inhibits autophagy of cisplatin-resistant testicular cancer cells by mediating ATP release. (Pubmed Central) - Jul 17, 2022 We found that cisplatin-resistant I-10 testicular cancer cell lines (I-10/CDDP) autophagy-associated proteins (p62, p-mTOR, mTOR and LC3) exhibited high levels of autophagy in their expression, while LC3-II expression was more significantly in the presence of lysosomal degradation blocked by chloroquine (CQ)...In addition, inhibition of Panx-1 by carbenoxolone (CBX) and probenecid (PBN), as well as shRNA-mediated knockdown promoted autophagy in the I-10/CDDP cells, which was accompanied by a decrease in the levels of extracellular ATP...Apyrase promoted autophagy in I-10/CDDP cells city by decreasing extracellular ATP, regardless of Panx-1 expression. This study demonstrated for the first time that Panx-1-mediated ATP release inhibits autophagy of I-10/CDDP cells, which provides a potential therapeutic strategy for cisplatin-resistant testicular cancer.
- |||||||||| MRT68921 / University of Dundee
Journal: STAT3 suppresses the AMPKα/ULK1-dependent induction of autophagy in glioblastoma cells. (Pubmed Central) - Jul 17, 2022 Inhibition of ULK1 activity (by treatment with MRT68921) or its expression (by siRNA knockdown) in STAT3-KO cells inhibits autophagy and sensitizes cells to apoptosis. Taken together, our findings suggest that serine and tyrosine phosphorylation of STAT3 play critical roles in STAT3-dependent autophagy in GBM, and thus are potential targets to treat GBM.
- |||||||||| sirolimus / Generic mfg.
Journal: Salmonella Promotes Its Own Survival in B Cells by Inhibiting Autophagy. (Pubmed Central) - Jul 17, 2022 In this study, we found that SopB activates mTORC1, which is necessary for bacterial survival, since B cells cultured with the mTORC1 inhibitor rapamycin and B cells lacking raptor can control Salmonella infection...In this study, we did not observe these results when B cells were infected with Δsopb Salmonella. Our results demonstrated that Salmonella survival within B cells depends on the inhibition of autophagy by mTORC1 activation.
- |||||||||| sirolimus / Generic mfg.
Journal: Resveratrol induces autophagy impeding BAFF-stimulated B-cell proliferation and survival by inhibiting the Akt/mTOR pathway. (Pubmed Central) - Jul 16, 2022 Inhibition of mTOR with rapamycin or knockdown of mTOR potentiated resveratrol-induced autophagy and inhibition of hsBAFF-stimulated B-cell proliferation/viability, while overexpression of wild-type mTOR conferred resistance to the actions of resveratrol...Taken together, these results indicate that resveratrol induces autophagy impeding BAFF-stimulated proliferation and survival via blocking the Akt/mTOR signaling pathway in normal and neoplastic B cells. Our findings highlight that resveratrol has a great potential for prevention and treatment of excessive BAFF-elicited aggressive B-cell disorders and autoimmune diseases.
- |||||||||| vinblastine / Generic mfg.
Journal: Intracellular accumulation of tau inhibits autophagosome formation by activating TIA1-amino acid-mTORC1 signaling. (Pubmed Central) - Jul 16, 2022 Our results indicated that spautin-1 may represent an attractive mitochondria-targeted seed compound that inhibits the UPR and cancer cell survival during glucose starvation. Our findings reveal that AD-like tau accumulation inhibits autophagosome formation and induces autophagy deficits by activating the TIA1/amino acid/mTORC1 pathway, and thus this work reveals new insight into tau-associated neurodegeneration and provides evidence supporting the use of new therapeutic targets for AD treatment and that of related tauopathies.
- |||||||||| Journal: Curcumin effect on Acanthamoeba triangularis encystation under nutrient starvation. (Pubmed Central) - Jul 13, 2022
Curcumin inhibits cyst formation in surviving trophozoites, which may result from its effect on mRNA expression of key Acanthamoeba ATG-related genes. However, further investigation into the mechanism of curcumin in A. triangularis trophozoites arrest and its association with autophagy or other encystation-related pathways is needed to support the future use of curcumin.
- |||||||||| sirolimus / Generic mfg.
Preclinical, Journal: High-altitude hypoxia-induced rat alveolar cell injury by increasing autophagy. (Pubmed Central) - Jul 13, 2022 Wistar rats were randomized into four groups for exposure to normal altitude or high altitude for 1, 7, 14 and 21 days with no treatment or with the treatment of 1 mg/kg rapamycin or 2 mg/kg 3-methyladenine (3-MA) for consecutive 21 days respectively...In conclusion, exposure to high-altitude hypoxia can induce autophagy of alveolar cells, which may be an important mechanism of high-altitude hypoxia-induced lung injury. The inhibition of autophagy may be a promising therapy strategy for high-altitude hypoxia-induced lung injury.
- |||||||||| sirolimus / Generic mfg.
Journal: Inhibition of Gas6 promotes crystalline silica-induced inflammatory response of macrophages via blocking autophagy flux. (Pubmed Central) - Jul 13, 2022 Besides, inhibition of Gas6 aggravated CS-induced inflammatory response, and autophagy inhibition facilitated the promoted effect of Gas6 silencing, resulting in elevated expression of inflammatory cytokines. These findings reveal the protective effects of Gas6 and autophagy in macrophages in response to CS exposure, and highlight the autophagy regulated by Gas6 may be a potential prevention target for CS-induced lung inflammatory response.
- |||||||||| Preclinical, Journal: PM2.5 Synergizes With Pseudomonas aeruginosa to Suppress Alveolar Macrophage Function in Mice Through the mTOR Pathway. (Pubmed Central) - Jul 10, 2022
In addition, alveolar macrophages had significantly increased expression of mTOR pathway-related proteins in response to the synergistic stimulation of PM2.5 and P. aeruginosa. The above results confirmed that PM2.5 in poultry houses synergized with P. aeruginosa to impede alveolar macrophage function and caused more severe respiratory system injuries through a process closely related to the activation of the mTOR signalling pathway.
- |||||||||| Journal: Tracking autophagy process with a through bond energy transfer-based ratiometric two-photon viscosity probe. (Pubmed Central) - Jul 9, 2022
Under 810 nm two-photon excitation, the emission intensity ratio of the red and green channel increased with a viscosity dependent manner. Lyso-Vis not only for the first time realized ratiometric sensing of lysosomal viscosity during autophagy process, but also visualized the association of autophagy with inflammation and stroke, and it was applied to explore the activation and inhibition of autophagy during stroke in mice.
- |||||||||| hydroxychloroquine / Generic mfg.
Journal: Trident Molecule with Nanobrush-Nanoparticle-Nanofiber Transition Property Spatially Suppresses Tumor Metastasis. (Pubmed Central) - Jul 9, 2022 Herein, by rational design of a trident molecule Nap-Phe-Phe-Lys(SA-CPT)-Lys(SA-HCQ)-Tyr(HPO)-OH (Nap-CPT-HCQ-Yp) with three functional "spears" (i.e., a phosphotyrosine motif for enzymatic self-assembly, camptothecin (CPT) motif for chemotherapy, and hydroxychloroquine (HCQ) motif for autophagy inhibition) and nanobrush-nanoparticle-nanofiber transition property, we propose a novel strategy of intracellular enzymatic nanofiber formation and synergistic autophagy inhibition-enhanced chemotherapy and immunotherapy for spatial suppression of tumor metastasis...Finally, a combination of checkpoint blockade therapy and Nap-CPT-HCQ-Yp-mediated chemotherapy elicits systemic antitumor immunity, thereby achieving efficient inhibitions of primary tumors as well as distant tumors in a breast tumor model. Our work offers a simple and feasible strategy for the design of "smart" multifunctional prodrugs to spatially suppress tumor metastasis.
- |||||||||| Preclinical, Journal: Inhibition of Porcine Epidemic Diarrhea Virus by Cinchonine via Inducing Cellular Autophagy. (Pubmed Central) - Jul 9, 2022
Cinchonine treatment could inhibit PEDV replication in a dose-dependent manner in Vero CCL81 cells, while this phenomenon disappeared when autophagy was attenuated by pre-treatment with autophagy inhibitor 3MA. Consequently, this study indicated that cinchonine can inhibit PEDV replication via inducing cellular autophagy and thus from the basis for successful antiviral strategies which potentially suggest the possibility of exploiting cinchonine as a novel antiviral agent.
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