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  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Melatonin Protects HT22 Hippocampal Cells from H2O2-induced Injury by Increasing Beclin1 and Atg Protein Levels to Activate Autophagy. (Pubmed Central) -  Apr 27, 2021   
    Rapamycin (an activator of autophagy) and 3-methyladenine (3MA, an inhibitor of autophagy) were used to induce or inhibit autophagy, respectively...The effects of melatonin on H2O2-induced injury, autophagy and protein expressions were effectively reversed by 3MA. In conclusion, these results demonstrate that melatonin protects HT22 hippocampal neurons from H2O2- induced injury by increasing the levels of the Beclin1 and Atg proteins to activate autophagy.
  • ||||||||||  Journal:  Impaired lipophagy in endothelial cells with prolonged exposure to oxidized low‑density lipoprotein. (Pubmed Central) -  Apr 27, 2021   
    Electron microscopy demonstrated that the formation of autolipophagosomes was decreased in ox‑LDL‑treated human umbilical vein ECs compared with that in the LDL‑treated group and was accompanied by a decrease in the autophagy‑associated proteins via western blotting analysis. Using laser focal colocalization detection, decreased lipid processing was observed in the lysosomes of ox‑LDL‑treated ECs, which indicated that lipophagy may be attenuated and subsequently result in lipid accumulation in ox‑LDL‑treated ECs.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  BIX-01294-enhanced chemosensitivity in nasopharyngeal carcinoma depends on autophagy-induced pyroptosis. (Pubmed Central) -  Apr 27, 2021   
    Furthermore, the inhibition of autophagy by chloroquine and the knockout of ATG5 gene significantly blocked the BIX-induced autophagy as well as pyroptosis in both in vitro and in vivo studies. Our data demonstrated that BIX-combined chemotherapeutic drugs could induce the Bax/caspase-3/GSDME-mediated pyroptosis through the activation of autophagy to enhance the chemosensitivity in NPC.
  • ||||||||||  Journal:  Microbial Metabolite Sodium Butyrate Attenuates Cartilage Degradation by Restoring Impaired Autophagy and Autophagic Flux in Osteoarthritis Development. (Pubmed Central) -  Apr 27, 2021   
    The protective effects of NaB could be partially abolished by the autophagy inhibitor 3-methyladenine (3-MA), which indicated that the protective effects of NaB against OA were partially governed by the enhancement of autophagy to restrain the formation of inflammatory mediators and ROS and regulate cell cycle progression and apoptosis in chondrocytes. In conclusion, NaB could attenuate OA progression by restoring impaired autophagy and autophagic flux via the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, both in vitro and in vivo, implying that NaB could represent a novel therapeutic approach for OA.
  • ||||||||||  Journal:  Autophagy regulates trophoblast invasion by targeting NF-κB activity. (Pubmed Central) -  Apr 24, 2021   
    Autophagy inhibition was also associated with increased MMP-2 and MMP-9 levels and decreased the production of sFlt-1 and TNF-α. Collectively, our results indicate that autophagy regulates trophoblast invasiveness in which the NF-κB pathway and MMP-2, MMP-9, sFlt-1 and TNF-α levels are affected.
  • ||||||||||  Journal:  RNF115 deletion inhibits autophagosome maturation and growth of gastric cancer. (Pubmed Central) -  Apr 24, 2021   
    These findings indicate that RNF115 may play an evolutionarily conserved role in the autophagy pathway, and may act to maintain protein homeostasis under physiological conditions. These data demonstrate the need to further evaluate the potential therapeutic implications of RNF115 in gastric cancer.
  • ||||||||||  Journal:  Autophagy modulates mesenchymal-to-endothelial transition via p53. (Pubmed Central) -  Apr 24, 2021   
    Moreover, after knockout of nuclear p53, autophagy promoted MEndT, while autophagy inhibited MEndT in p53 overexpressing cells. Our results demonstrate that autophagy modulate MEndT by nuclear p53 provide a new strategy for the treatment of fibrosis diseases.
  • ||||||||||  Journal:  Eva1a inhibits NLRP3 activation to reduce liver ischemia-reperfusion injury via inducing autophagy in kupffer cells. (Pubmed Central) -  Apr 24, 2021   
    We also found that the addition of siATG7, siATG5 and siATG12 would reverse the IR autophagy of liver induced by overexpression of Eva1a, but inhibition of the Beclin1-Vps34 pathway did not significantly reverse the effect of overexpression of Eva1a.These prove that Eva1a and ATG16L1 may work together in the liver IR model to actively induce the formation of autophagosomes and be independent from the beclin1-vps34-induced autophagy pathway to limit the excessive activation of IR inflammation. Our study provides brand new insights into the mechanism of liver macrophages in the progression of inflammation in the context of liver ischemia-reperfusion injury.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Vitamin D/VDR Protects Against Diabetic Kidney Disease by Restoring Podocytes Autophagy. (Pubmed Central) -  Apr 24, 2021   
    Our study delivered the evidence that calcitriol/VDR signaling attenuated diabetic nephropathy and podocytes injury by restoring podocytes autophagy. This finding may have potential implication for exploring protective mechanisms of calcitriol/VDR in diabetic nephropathy.
  • ||||||||||  hydroxychloroquine / Generic mfg., albumin-bound paclitaxel / Generic mfg., gemcitabine / Generic mfg.
    Trial completion date, Trial primary completion date, Combination therapy:  A Phase I/II/Pharmacodynamic Study of Hydroxychloroquine in Combination With Gemcitabine/Abraxane to Inhibit Autophagy in Pancreatic Cancer (clinicaltrials.gov) -  Apr 22, 2021   
    P1/2,  N=119, Active, not recruiting, 
    Overall, this evidence demonstrated that CPZ is a novel promising strategy for the treatment of oral cancer. Trial completion date: Mar 2021 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021
  • ||||||||||  Journal:  ZNF295-AS1 inhibits autophagy via the ZNF295-AS1/miR-508-5p/ATG7 axis in AS. (Pubmed Central) -  Apr 22, 2021   
    Overall, our findings demonstrate a novel mechanism by which ZNF295-AS1 silencing regulates ATG7 reduction and inhibits autophagy, which may delay the progression of AS. The ZNF295-AS1/miR-508-5p/ATG7 axis may be of therapeutic significance in AS.
  • ||||||||||  Journal, IO biomarker:  EGFR-independent EGFR-mutant lung adenocarcinoma cells depend on Bcl-xL and MCL1 for survival. (Pubmed Central) -  Apr 21, 2021   
    However, autophagy inhibition was inferior to dual inhibition of Bcl-xL plus MCL1 for GR2 cells, or MCL1 inhibition alone, for decreasing the viability of WR7 cells. Collectively, these findings suggest that inhibiting Bcl-xL plus MCL1, or MCL1 alone, may represent a new approach to treat EGFR-independent EGFR-mutant cancer cells.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  The critical role of PPARα in the binary switch between life and death induced by endoplasmic reticulum stress. (Pubmed Central) -  Apr 21, 2021   
    Tunicamycin (TM) and thapsigargin (TG), as ER stress inducers, were used to induce ER stress in AML12 cells...In the mild-ER stress with PPARα knocked down, activation of autophagy by rapamycin significantly improved cell survival, in the serious ER stress with PPARα activation, inhibition of autophagy by 3-MA aggravate cell injury...Furthermore, C57BL/6 mice was used to induce ER stress with TM intraperitoneal injection, PPARα and autophagy was upregulated in the mild-ER stress while downregulated in the serious ER stress, measured by qRT-PCR and immunoblotting, further confirmed the finding in vitro. Our results firstly demonstrated that PPARα is a key molecule in the functional conversion of ER stress: protective effects in the mild ER stress was mediated by PPARα-autophagy pathway and destructive effects in the serious ER stress was mediated by PPARα-CHOP pathway.
  • ||||||||||  Journal:  Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells. (Pubmed Central) -  Apr 21, 2021   
    Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.
  • ||||||||||  hydroxychloroquine / Generic mfg.
    Journal:  Autophagy Inhibitors Do Not Restore Peroxisomal Functions in Cells With the Most Common Peroxisome Biogenesis Defect. (Pubmed Central) -  Apr 21, 2021   
    In contrast to L-arginine, we observed no improvement but a worsening of peroxisomal metabolic functions and peroxisomal matrix protein import by the autophagy inhibitors, while genetic knock-down of ATG5 and NBR1 in primary patient cells resulted in only a minimal improvement. Our results do not support the use of autophagy inhibitors as potential treatment for PBD-ZSD patients, whereas L-arginine remains a therapeutically promising compound.
  • ||||||||||  cytarabine / Generic mfg.
    Journal:  Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine. (Pubmed Central) -  Apr 20, 2021   
    Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease.
  • ||||||||||  [VIRTUAL] Arginine deprivation therapy induces apoptotic cell death in melanoma brain metastasis () -  Apr 18, 2021 - Abstract #EADOWCM2021EADO-WCM_694;    
    Cell death mechanism is via impaired oxidative phosphorylation, leading to mitochondrial fragmentation, ROS release and the induction of intrinsic apoptosis, in MBM. While apoptotic cell death was observed in all models, the initial induction of autophagy could pose threat of resistance development in a clinical setting, and so combinational therapies with autophagic inhibitors and/or additional apoptotic inducers should be investigated.
  • ||||||||||  doxorubicin hydrochloride / Generic mfg.
    [VIRTUAL] A New AMPK Activator PA-S14 Attenuates Renal Injury through Promoting Autophagy () -  Apr 17, 2021 - Abstract #ISNWCN2021ISN-WCN_954;    
    Methods Bal/bc mice were performed unilateral ureteral obstruction (UUO), unilateral ischemia-reperfusion injury (UIRI) surgery, or injected with adriamycin (ADR)...Conclusions In summary, our results demonstrate that PA-S14 acts as a new AMPK activator to protect against renal fibrosis. The underlying mechanisms are related to PA-S14-induced AMPK activation, which further promotes autophagy through regulating mTOR pathway.
  • ||||||||||  Review, Journal:  Autophagy as a therapeutic target in pancreatic cancer. (Pubmed Central) -  Apr 16, 2021   
    Although the molecular mechanisms of autophagy activation in PDAC are only beginning to emerge, several groups have reported interesting results when combining inhibitors of the extracellular-signal-regulated kinase/mitogen-activated protein kinase pathway and inhibitors of autophagy in models of PDAC and other KRAS-driven cancers. In this article, we review the existing preclinical data regarding the role of autophagy in PDAC, as well as results of relevant clinical trials with agents that modulate autophagy in this cancer.