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Journal: Role of mTOR through Autophagy in Esophageal Cancer Stemness. (Pubmed Central) - Apr 13, 2022 Here, we aim to clarify the role of the hypoxia-responding mammalian target of the rapamycin (mTOR) pathway in esophageal CSCs...Torin-1-mediated CSCs upregulation was significantly reduced in cells treated with autophagy inhibitor, hydroxychloroquine (HCQ)...These data suggest that autophagy may play a crucial role in mTOR-mediated CSCs repression. Stimulation of the mTOR pathway might aid in the elimination of putative esophageal CSCs.
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Journal: Effect of autophagy on ferroptosis in foam cells via Nrf2. (Pubmed Central) - Apr 12, 2022 The effect of autophagy through Nrf2 on ferroptosis in foam cells was determined. The results revealed that insufficient autophagy in CQ-induced foam cells could lead to foam cell death in atherosclerotic plaques, and the cause of cell death was that insufficient autophagy in foam cells turned off the positive effect of Nfr2 antioxidant, initiated the negative effect of Nrf2 to promote intracellular reactive oxygen species production, and this negative effect promoted ferroptosis in foam cells.
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Using this tool, the fluorescence lifetime imaging can quantitatively determine the degrees of ER destruction and spontaneous recovery. Significantly, we show that triglycerides supplied in lipid droplets can efficiently repair ER via the two critical pathways: (i) supplying materials for ER repair by converting triglycerides into fatty acids and diglycerides and (ii) partially inhibiting autophagy for stressed ER.
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Journal: Modulation of Intestinal Epithelial Permeability via Protease-Activated Receptor-2-Induced Autophagy. (Pubmed Central) - Apr 12, 2022 When PAR2 was activated, intestinal permeability was maintained, but when autophagy was suppressed by chloroquine, intestinal permeability was significantly increased...In conclusion, regulating intestinal epithelial permeability through PAR2-induced autophagy can help maintain mucosal barrier integrity. Therefore, these findings suggest that the regulation of PAR2 can be a suitable strategy to treat intestinal diseases caused by permeability dysfunction.
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The fluorescence colocalization of LC3-CD63 and the inhibition of autophagy and exosome signaling pathway further revealed that H1N1 infection seemed to sequentially activate the M1 polarization and recruitment of macrophages via autophagy-exosome dependent pathway. Autophagy and exosome production coordinately enhance the M1 polarization and recruitment of macrophages in influenza virus infection, which also provides potential therapeutic targets.
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Journal: Ming-Mu-Di-Huang-Pill Activates SQSTM1 via AMPK-Mediated Autophagic KEAP1 Degradation and Protects RPE Cells from Oxidative Damage. (Pubmed Central) - Apr 12, 2022 The MMDH pill mediated Kelch-like ECH-associated protein 1 (Keap1) degradation and decreased oxidative damage, which was blocked in autophagy inhibitor (chloroquine) or sequestosome-1 (SQSTM1) siRNA-treated RPE cells...In conclusion, MMDH pill plays a protective role in relieving NaIO-induced oxidative stress by activating the AMPK/SQSTM1/Keap1 pathway. The MMDH pill may be useful to treat AMD by maintaining redox homeostasis and autophagy.
- |||||||||| ibandronate sodium hydrate / Generic mfg.
Preclinical, Journal: Ibandronate promotes autophagy by inhibiting Rac1-mTOR signaling pathway in vitro and in vivo. (Pubmed Central) - Apr 12, 2022 Furthermore, the in vivo experiments also indicated that IBAN promotes autophagy by downregulating Rac1-mTOR. Taken together, our results firstly revealed that IBAN enhances autophagy via inhibiting Rac1-mTOR signaling pathway, and thus alleviates Ang II-induced injury in endothelial cells.
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Trial completion date, Trial primary completion date: The Addition of Chloroquine to Chemoradiation for Glioblastoma, (clinicaltrials.gov) - Apr 12, 2022 P2, N=156, Not yet recruiting, Inhibition of JNK and ERK in the MAPK signaling family alleviated TL-induced CESC degeneration by inhibiting the phosphorylation of Raptor and mTOR in the mTOR pathway. Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
- |||||||||| Journal: TRIM65 Promotes Cervical Cancer Through Selectively Degrading p53-Mediated Inhibition of Autophagy and Apoptosis. (Pubmed Central) - Apr 12, 2022
Furthermore, our experiments showed that TRIM65 exhibited oncogenic activities via directly targeting p53, a tumor suppressor and a common upsteam regulator between autophagy and apoptosis, promoting ubiquitination and proteasomal degradation of p53. Taken together, our studies demonstrated that TRIM65 knockdown promotes cervical cancer cell death through enhancing autophagy and apoptosis, suggesting that TRIM65 may be a potential therapeutic target for cervical cancer clinically.
- |||||||||| metformin / Generic mfg.
Protective role of metformin in acute renal ischemic reperfusion injury (Room 225) - Apr 10, 2022 - Abstract #AUA2022AUA_1774; Conclusions : Altogether, in this research, we established IR mouse model of kidney stone. We firstly found metformin inhibits autophagy and apoptosis in renal cell, which indicated metformin plays a protective role of metformin in acute renal ischemic reperfusion injury.
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Journal: The anticancer drug imatinib induces autophagy in Schistosoma mansoni. (Pubmed Central) - Apr 9, 2022 Here, we present the first known evidence that one effect of imatinib is the induction of autophagy in S. mansoni. Furthermore, worms co-treated with imatinib and bafilomycin A1, a late-phase autophagy inhibitor, reversed imatinib-induced autophagy and its antischistosomal effects as revealed by phenotypic and molecular analyses.
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Downregulation of lncTRPM2-AS significantly decreased intracellular calcium levels by restraining TRPM2 protein expression, which in turn decreased ROS levels and increased autophagy to promote macrophage apoptosis and reduce cytokine production, together inhibiting macrophage inflammation. Taken together, our findings demonstrate that lncTRPM2-AS blocks the ubiquitination of TRPM2 via TRIM21 and inhibits autophagy-induced apoptosis which may contribute to macrophage inflammation in asthma.
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Journal, IO biomarker: Pan-Caspase Inhibitor zVAD Induces Necroptotic and Autophagic Cell Death in TLR3/4-Stimulated Macrophages. (Pubmed Central) - Apr 9, 2022 Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.
- |||||||||| Journal: Autolysosomes and caspase-3 control the biogenesis and release of immunogenic apoptotic exosomes. (Pubmed Central) - Apr 9, 2022
Caspase-3 activation was identified using caspase-3-deficient endothelial cells or caspase inhibitors as a pivotal regulator of fusion events between autolysosomes and the cell membrane, therefore regulating the release of immunogenic ApoExos. Collectively, these findings identified autolysosomes as a site of ApoExo biogenesis and caspase-3 as a crucial regulator of autolysosome cell membrane interactions involved in the secretion of immunogenic ApoExos.
- |||||||||| Review, Journal: Autophagy Contributes to Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Tumors. (Pubmed Central) - Apr 9, 2022
Moreover, high autophagic activity in PDAC is markedly related to resistance to current therapies. In this context, combining autophagy inhibition with standard chemotherapy, and/or drugs targeting other vulnerabilities such as metabolic pathways or the immune response, is an ongoing clinical strategy for which there is still much to do through translational and multidisciplinary research.
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Thus, our data show that pathological protein S-nitrosylation of p62 represents a critical factor not only for autophagic inhibition and demise of individual neurons, but also for α-syn release and spread of disease throughout the nervous system.SIGNIFICANCE STATEMENTIn Parkinson's disease and Lewy body dementia, dysfunctional autophagy contributes to accumulation and spread of aggregated α-synuclein. Here, we provide evidence that protein S-nitrosylation of p62 inhibits autophagic flux, contributing to α-synuclein aggregation and spread.
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Journal: Knockdown of lncRNA HAGLROS inhibits metastasis and promotes apoptosis in nephroblastoma cells by inhibition of autophagy. (Pubmed Central) - Apr 9, 2022 Rapamycin and 3-methyladenine were used to serve as autophagy activator or inhibitor, respectively...Stimulation of autophagy alleviated HAGLROS silencing-induced apoptosis, while inhibition of autophagy reversed the effect in nephroblastoma cells. In summary, our results revealed that HAGLROS executed an oncogenic role in the progress of nephroblastoma, offering a new perspective on the strategy for nephroblastoma therapy.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal, IO biomarker: Inhibition of autophagy enhances apoptosis induced by doxorubicin hydrochloride in human colon cancer cells (Pubmed Central) - Apr 9, 2022 Results DOX inhibited the proliferation and colony formation of colon cancer cells, and promoted cell apoptosis in a concentration-dependent manner; DOX promoted autophagy in cells, and the expression of beclin 1 and LC3 II increased in a concentration-dependent manner; DOX promoted apoptosis of colon cancer cells, which was improved by inhibiting autophagy. Conclusion DOX inhibits the proliferation of colon cancer cells and promotes their apoptosis, and inhibition of autophagy in colon cancer cells can increase the sensitivity of apoptosis induced by DOX.
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At the cellular level, we found that CCL2 induction via autophagy in keratinocytes is required not only for keratinocyte migration and proliferation but also for dermal fibroblast activation. Our findings demonstrate a critical role of epidermal autophagy in wound healing in vivo and elucidate a critical molecular machinery coordinating keratinocyte-fibroblast interaction in skin repair.
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Journal: TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation. (Pubmed Central) - Apr 8, 2022 Targeting TXNIP may be a potential therapeutic approach for NASH. Abbreviations: ACOX1: acyl-Coenzyme A oxidase 1, palmitoyl; ACSL1: acyl-CoA synthetase long-chain family member 1; ACTA2/α-SMA: actin, alpha 2, smooth muscle, aorta; ACTB: actin beta; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; AMPK: AMP-activated protein kinase; ATG: autophagy-related; BafA1: bafilomycin A1; COL1A1/Col1α1: collagen, type I, alpha 1; CPT1A: carnitine palmitoyltransferase 1a, liver; CQ: chloroquine; DGAT1: diacylglycerol O-acyltransferase 1; DGAT2: diacylglycerol O-acyltransferase 2; ECI2/Peci: enoyl-Coenzyme A isomerase 2; EHHADH: enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase; FAO: fatty acid oxidation; FASN: fatty acid synthase; FFA: free fatty acids; GFP: green fluorescent protein; GK/GYK: glycerol kinase; GOT1/AST: glutamic-oxaloacetic transaminase 1, soluble; GPAM: glycerol-3-phosphate acyltransferase, mitochondrial; GPT/ALT: glutamic pyruvic transaminase, soluble; H&E: hematoxylin and eosin; IL1B/IL-1β: interleukin 1 beta; IL6: interleukin 6; IOD: integral optical density; KO: knockout; Leu: leupeptin; LPIN1: lipin 1; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MCD: methionine choline-deficient; MMP9: matrix metallopeptidase 9; mRNA: messenger RNA; MTORC1: mechanistic target of rapamycin kinase complex 1; NAFLD: nonalcoholic fatty liver diseases; NASH: nonalcoholic steatohepatitis; PA: palmitic acid; PPARA/PPARα: peroxisome proliferator activated receptor alpha; PPARG/PPARγ: peroxisome proliferator activated receptor gamma; qRT-PCR: quantitative real-time PCR; RPS6KB1/p70S6K1: ribosomal protein S6 kinase, polypeptide 1; RPTOR: regulatory associated protein of MTOR complex 1; SCD1: stearoyl-Coenzyme A desaturase 1; SEM: standard error of the mean; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TG: triglyceride; TGFB/TGF-β: transforming growth factor, beta; TIMP1: tissue inhibitor of metalloproteinase 1; TNF/TNF-α: tumor necrosis factor; TXNIP/VDUP1: thioredoxin interacting protein; WT: wild-type.
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