- |||||||||| Journal: Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species-induced autophagy. (Pubmed Central) - Sep 25, 2021
Mechanistically, suppression of LETM1 increased the levels of reactive oxygen species (ROS) and mitochondrial ROS by regulation of SOD2, which in turn activated AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), initiated autophagy, and inhibited proliferation and stemness. Our findings suggest that silencing LETM1 induced autophagy in CRC cells by triggering ROS-mediated AMPK/mTOR signalling, thus blocking CRC progression, which will enhance our understanding of the molecular mechanism of LETM1 in CRC.
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[VIRTUAL] Autophagy Mediated Vesicular Trafficking Dysregulation in Hypertrophic Cardiomyopathy (ePosters) - Sep 24, 2021 - Abstract #AHA2021AHA_1150; Conversely autophagy inhibition by chloroquine (10 mg/kg i.p.) exacerbated the blockade of exosome secretion...Similar troponin elevation and CD9/ALIX reduction were seen in plasma exosomes from HCM human patient samples with the FHOD3-V1151I genotype. Conclusions The cardiac autophagy and circulating exosome perturbations, reversible by autophagy modulation, raise intriguing possibilities in the early diagnosis and treatment of HCM
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Journal, IO biomarker: PLCγ1 inhibition-driven autophagy of IL-1β-treated chondrocyte confers cartilage protection against osteoarthritis, involving AMPK, Erk and Akt. (Pubmed Central) - Sep 24, 2021 Using Western blotting, immunoprecipitation, qPCR, immunofluorescence and Dimethylmethylene blue assays, and ELISA and transmission electron microscope techniques, we found that PLCγ1 inhibitor U73122 enhanced Collagen II, Aggrecan and GAG levels, accompanied with increased LC3B-II/I ratio and decreased P62 expression level, whereas autophagy inhibitor Chloroquine partially diminished its effect...Additionally, by haematoxylin and eosin, Safranin O/Fast green, and immunohistochemistry staining, we observed that intra-articular injection of Ad-shPLCγ1-1/2 significantly enhanced Collagen and Aggrecan levels, accompanied with increased LC3B and decreased P62 levels in a rat OA model induced by anterior cruciate ligament transection and medial meniscus resection. Consequently, PLCγ1 inhibition-driven autophagy conferred cartilage protection against OA through promoting ECM synthesis in OA chondrocytes in vivo and in vitro, involving the crosstalk between PLCγ1, AMPK, Erk and Akt.
- |||||||||| Journal: The aberrant expression in epithelial cells of the mesenchymal isoform of FGFR2 controls the negative crosstalk between EMT and autophagy. (Pubmed Central) - Sep 24, 2021
Biochemical, molecular, quantitative immunofluorescence analysis and in vitro invasion assays, coupled to the use of specific substrate inhibitors and transient or stable silencing approaches, showed that AKT/MTOR and PKCε are the two hub signalling pathways, downstream FGFR2c, intersecting with each other in the control of both the inhibition of autophagy and the induction of EMT and invasive behaviour. These results indicate that the expression of FGFR2c, possibly resulting from FGFR2 isoform switch, could represent a key upstream event responsible for the establishment of a negative interplay between autophagy and EMT, which contributes to the assessment of a pathological oncogenic profile in epithelial cells.
- |||||||||| Journal: MicroRNA-130a inhibits proliferation of vascular smooth muscle cells by suppressing autophagy via ATG2B. (Pubmed Central) - Sep 24, 2021
In addition, by using immunohistochemistry, the positive results of LC3 II/I and ATG2B in the rat model and artery vascular tissues from the patient were in accordance with in vitro data. In conclusion, our data demonstrate that miR-130a inhibits VSMCs proliferation via ATG2B, which indicates that miR-130a could be a potential therapeutic target that regulates autophagy in atherosclerosis obliterans.
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Journal: Therapeutic Approach of KRAS Mutant Tumours by the Combination of Pharmacologic Ascorbate and Chloroquine. (Pubmed Central) - Sep 24, 2021 We predicted that the addition of both pharmacologic ascorbate and chloroquine is able to block both KRAS and mTOR pathways: in this case, no GLUT1 expression is observed, meanwhile autophagy, essential for KRAS mutant cancer cells, is blocked. Corresponding to our system biological analysis, this combined pharmacologic ascorbate and chloroquine treatment in KRAS mutant cancers might be a therapeutic approach in anti-cancer therapies.
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Journal: Pulmonary Surfactants Affinity Pluronic-Hybridized Liposomes Enhance the Treatment of Drug-Resistant Lung Cancer. (Pubmed Central) - Sep 24, 2021 On the other hand, drug-resistant tumor cells were resensitized due to the inhibition of autophagy by Ax and the reduced expression of the drug-resistant protein P-glycoprotein (P-gp) by Pluronic P105. Therefore, we concluded that the combination of PPL and Ax achieved excellent killing tumor effects through multi-path and multi-strategy, having great application prospects in the future.
- |||||||||| Review, Journal: The functions of autophagy at the tumour-immune interface. (Pubmed Central) - Sep 23, 2021
Broad targeting of autophagy may not yield maximal benefits. The characterization of specific genes regulating tumour immunogenicity and innovation in targeted delivery of autophagy inhibitors into certain tumours are among the most urgent tasks to sensitize cold cancers to immunotherapy.
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Preclinical, Journal: 7,8-dihydroxyflavone ameliorates motor deficits via regulating autophagy in MPTP-induced mouse model of Parkinson's disease. (Pubmed Central) - Sep 22, 2021 We found that the administration of DHF (5 mg/kg/day, i.p.) prevented the loss of dopaminergic neurons and improved motor functions in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, whereas these protective effects of DHF were completely blocked by autophagy inhibitor chloroquine (CQ)...DHF restored the impaired autophagy to control level in MPP-treated N2A cells by inhibiting the ERK-LKB1-AMPK signaling pathway. Taken together, these results demonstrate that DHF exerts therapeutic effects in MPTP/MPP-induced neurotoxicity by inhibiting the ERK-LKB1-AMPK signaling pathway and subsequently improving impaired autophagy.
- |||||||||| Journal: CaMKII Oxidation Regulates Cockroach Allergen-Induced Mitophagy in Asthma. (Pubmed Central) - Sep 22, 2021
Taken together, this study demonstrates that the anti-PD role of GM1 ganglioside resulted from activation of autophagy-dependent α-Syn clearance. Our data suggest a previously uncovered axis of allergen-ROS-ox-CaMKII-mitophagy in the development of allergic airway inflammation and asthma.
- |||||||||| Journal: YAP plays a crucial role in the development of cardiomyopathy in lysosomal storage diseases. (Pubmed Central) - Sep 22, 2021
YAP physically interacted with transcription factor EB (TFEB), a master transcription factor that controls autophagic and lysosomal gene expression, thereby facilitating accumulation of autophagosomes without degradation. These results indicate that accumulation of YAP in the presence of LSD promotes cardiomyopathy by stimulating accumulation of autophagosomes through activation of TFEB.
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Journal: Identification of madangamine A as a novel lysosomotropic agent to inhibit autophagy. (Pubmed Central) - Sep 22, 2021 Moreover, madangamine A resulted in lysosome enlargement and increase in lysosomal pH, which are same phenomena observed in chloroquine-treated cells. These results suggest that madangamine A is a novel lysosome inhibitor, and the anti-proliferative activity of madangamine A is due to the inhibition of lysosome function.
- |||||||||| Journal: AMPK activation by ASP4132 inhibits non-small cell lung cancer cell growth. (Pubmed Central) - Sep 22, 2021
AMPK activation, mTORC1 inhibition and EGFR-PDGFRα degradation as well as Akt inhibition and autophagy induction were detected in ASP4132-treated NSCLC xenograft tumor tissues. Together, activation of AMPK by ASP4132 potently inhibits NSCLC cell growth in vitro and in vivo.
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Journal: New insights into crosstalk between pyroptosis and autophagy co-induced by molybdenum and cadmium in duck renal tubular epithelial cells. (Pubmed Central) - Sep 22, 2021 Hence, the cells were treated with 500.0 μM Mo, 4.0 μM Cd, 10.0 μM Z-YVAD-fluoromethylketone (YVAD), 2.5 μM 3-methyladenine (3-MA) and 10.0 μM chloroquine (CQ) alone or in combination for 12 h (CQ for the last 4 h)...Besides, both 3-MA and CQ addition increased NLRP3, Caspase-1, NEK7, ASC, GSDMA, GSDME, IL-1β, IL-18 mRNA levels, NLRP3, Caspase-1 p20, ASC, GSDMD protein and ROS levels, and NO, LDH, IL-1β, IL-18 releases. Collectively, our results revealed that pyroptosis and autophagy co-induced by Mo and Cd were interrelated in duck renal tubular epithelial cells, and inhibiting pyroptosis might attenuate Mo and Cd co-induced autophagy, but inhibiting autophagy might promote Mo and Cd co-induced pyroptosis.
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Journal: Toluene diisocyanate-induced inflammation and airway remodeling involves autophagy in human bronchial epithelial cells. (Pubmed Central) - Sep 19, 2021 3-Methyladenine (3-MA) and Rapamycin (Rapa) intervention were used to explore the effects of autophagy on inflammatory response and protein expression related to airway remodeling in 16HBE cells treated with TDI-HSA...The treatment of TDI-HSA combined with Rapa aggravated the above reaction whereas the inverse was true for TDI-HSA combined with 3-MA. These results indicated that autophagy is involved in TDI-induced airway inflammation and airway remodeling as a positive regulatory mechanism, inhibiting autophagy can significantly alleviate the TDI-induced inflammatory response and attenuate airway remodeling protein expression in 16HBE cells.
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Preclinical, Journal: Effect of silibinin on ethanol- or acetaldehyde-induced damge of mouse primary hepatocytes in vitro. (Pubmed Central) - Sep 19, 2021 Consistently, silibinin (20 μM) significantly reduced the activation of caspase 3 or apoptosis and increased the conversion of LC3-I to LC3-II or autophagy. Taken together, it is concluded that silibinin does not repress the ethanol- induced hepatocyte injury, whereas silibinin reduces acetaldehyde-caused hepatocyte injury through down-regulation of apoptosis and up-regulation of autophagy.
- |||||||||| Licensing / partnership, Review, Journal: mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership. (Pubmed Central) - Sep 19, 2021
These functional connections suggest the existence of autophagy regulatory pathways in senescent cells that differ from those activated in non-senescence contexts. We envision that untangling these functional connections will be key for the generation of combinatorial anti-cancer therapies involving pro-senescence drugs, mTOR inhibitors, and/or autophagy inhibitors.
- |||||||||| Journal: CYR61, regulated by miR-22-3p and MALAT1, promotes autophagy in HK-2 cell inflammatory model. (Pubmed Central) - Sep 18, 2021
The use of miR-22-3p mimics significantly reversed the changes induced by up-regulation of CYR61 or MALAT1 at the molecular and cellular levels. Our data indicated that CYR61 positively regulates autophagy of HK-2 cells under an inflammatory state, and was negatively regulated by miR-22-3p, while miR-22-3p and MALAT1 were negatively regulated by each other.
- |||||||||| Journal: P53-regulated autophagy and its impact on drug resistance and cell fate. (Pubmed Central) - Sep 18, 2021
P53 can promote or inhibit autophagy depending on its subcellular localization, mutation status, and the level of stress. Blocking autophagy has been reported in several studies to increase p53-mediated apoptosis, revealing that autophagy can influence cell-fate in response to activated p53 and is a potential target to increase p53-dependent tumor suppression.
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Journal: Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans. (Pubmed Central) - Sep 17, 2021 Reconstitution of wild-type ATG4A and LC3B2 expression using lentiviral gene delivery or electroporation of in vitro transcribed mRNA into patient cells restored virus-induced autophagy and the ability to control HSV2 replication. This study describes a previously unknown link between defective autophagy and an inborn error of immunity that can lead to increased susceptibility to HSV2 infection, suggesting an important role for autophagy in antiviral immunity in the CNS.
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