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  • ||||||||||  Journal:  TRPML1-induced autophagy inhibition triggers mitochondrial mediated apoptosis. (Pubmed Central) -  Jun 11, 2022   
    As a result, by triggering apoptosis, TRPML1-induced autophagy inhibition greatly suppresses growth of human melanoma and glioma both in vitro and in vivo. In summary, our findings define the mechanism underling the regulation of autophagy inhibition in apoptosis and represent TRPML1 as a novel target for potentially treating melanoma and glioblastoma in the clinical setting.
  • ||||||||||  Journal:  Emendation of Autophagic Dysfuction in Neurological Disorders: A Potential Therapeutic Target. (Pubmed Central) -  Jun 9, 2022   
    This in-turn leads to accumulation of abnormal and unwanted protein aggregates and organelles thereby negatively affecting the neuronal function and survival. Hence, this review aims to understand the autophagic process, its impairment in various neurodegenerative and neuropsychiatric disorders along with certain molecules/compounds to fight those impairments.
  • ||||||||||  Preclinical, Journal:  Neuroprotective efficacy of berberine following developmental exposure to chlorpyrifos in F1 generation of Wistar rats: Apoptosis-autophagy interplay. (Pubmed Central) -  Jun 9, 2022   
    Moreover, BBR co-treatments reduced apoptotic neurodegeneration in the hippocampal region by regulating the expression of apoptotic genes and upregulated the levels of autophagy, confirmed by ultrastructural studies, decreased gene expression and immunostaining of mTOR and increased, and increased expression gene expression and immunostaining of LC3-II positive cells. Our results confirm that treatment with BBR induces autophagy, which plays a neuroprotective role in CPF-induced developmental neuronal apoptosis in the F1 generation of Wistar rats by regulating the balance between autophagy and apoptosis.
  • ||||||||||  cisplatin / Generic mfg.
    Journal:  MicroRNA-483-5p accentuates cisplatin-induced acute kidney injury by targeting GPX3. (Pubmed Central) -  Jun 8, 2022   
    Collectively, miR-483-5p is upregulated by cisplatin and exacerbates cisplatin-induced AKI via negative regulation of GPX3 and contributing oxidative stress and tubular cell apoptosis. These findings reveal a pathogenic role for miR-483-5p in cisplatin-induced AKI and suggest a novel target for the diagnosis and treatment of AKI.
  • ||||||||||  Repatha (evolocumab) / Amgen, Astellas
    Journal, IO biomarker:  PCSK9 inhibition protects against myocardial ischemia-reperfusion injury via suppressing autophagy. (Pubmed Central) -  Jun 8, 2022   
    PCSK9 is upregulated in the myocardial ischemia-reperfusion injury hearts and regulates mitophagy via the BNIP3 pathway, which in turn contributes to reperfusion injury after myocardial infarction. PCSK9 inhibition protects against myocardial ischemia-reperfusion injury via suppressing autophagy.
  • ||||||||||  Journal:  Induction of autophagy-dependent ferroptosis to eliminate drug-tolerant human retinoblastoma cells. (Pubmed Central) -  Jun 8, 2022   
    We evaluate the effectiveness and safety of 4-octyl itaconate, a cell-permeable derivative of the metabolite itaconate, in inducing ferritinophagy-dependent ferroptosis in the treatment of MDR RB cells in vitro and in xenograft mouse models. These findings may provide essential clues for initiating clinical trials that target autophagy-dependent ferroptosis to kill drug-tolerant persistent cells during RB therapy.
  • ||||||||||  Preclinical, Journal:  Autophagy Impairment in App Knock-in Alzheimer's Model Mice. (Pubmed Central) -  Jun 8, 2022   
    Double immunostaining for LC3 and Aβ revealed LC3-positive puncta in hippocampus of 24-month-old App mice around the Aβ plaques which was subsequently identified by electron microscopy imaging as an accumulation of autophagic vacuoles in dystrophic neurites around the Aβ plaques. Taken together, autophagy is impaired in App knock-in mice upon increased Aβ pathology, indicating that App knock-in mouse models provide a platform for understanding the correlation between Aβ and autophagy.
  • ||||||||||  Journal:  Hypoxia Induces Autophagy in Human Dendritic Cells: Involvement of Class III PI3K/Vps34. (Pubmed Central) -  Jun 5, 2022   
    The Vps34 inhibitor, SAR405, abolished hypoxia-induced autophagy, inhibited pro-survival signaling and viability, and increased the expression of proinflammatory cytokines. Our results underlined the impact of autophagy in the maintenance of DC homeostasis at both cell survival and inflammatory response levels, therefore, contributing to a better understanding of the significance of autophagy in DC physiology and pathology.
  • ||||||||||  deferoxamine / Generic mfg.
    Journal:  p53N236S Activates Autophagy in Response to Hypoxic Stress Induced by DFO. (Pubmed Central) -  Jun 5, 2022   
    In this study, we found that p53N236S (p53N239S in humans, hereinafter referred to as p53S) mutant mouse embryonic fibroblasts (MEFs) resistant to deferoxamine (DFO) mimic a hypoxic environment...In addition, the mitochondrial membrane potential (MMP) and the ROS level results indicated that p53S might initiate mitophagy to clear up damaged mitochondria in response to hypoxic stress, thus increasing the proportion of intact mitochondria and maintaining cell survival. In conclusion, the p53S mutant activates autophagy instead of inducing an apoptotic process in response to hypoxia stress to protect cells from death.
  • ||||||||||  chloroquine phosphate / Generic mfg., acetylcysteine solution / Generic mfg.
    Journal:  Crassolide Induces G2/M Cell Cycle Arrest, Apoptosis, and Autophagy in Human Lung Cancer Cells via ROS-Mediated ER Stress Pathways. (Pubmed Central) -  Jun 5, 2022   
    In conclusion, our findings show that crassolide inhibits NSCLC cell malignant biological behaviors for the first time, suggesting that this effect may be mechanistically achieved by inducing G2/M arrest, apoptosis, and autophagy through ROS accumulation, which activates the ER stress pathway. As a result of our findings, we now have a better understanding of the molecular mechanism underlying the anticancer effect of crassolide, and we believe crassolide might be a candidate for targeted cancer therapy.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility. (Pubmed Central) -  Jun 5, 2022   
    Similarly, treatment with the autophagy inhibitor chloroquine elevated LysoTracker fluorescence in both mouse cumulus cells and KGN cells, subsequently suppressing ovulation in female mice...Our results suggest that autophagy maintains the healthy state of the supporting cells of human oocytes by suppressing the formation of lysosomes. Thus, our results provide insights into the therapeutic effects of trehalose on female fertility.
  • ||||||||||  etomoxir (MIQ-001) - Meta / IQ
    Journal:  Metabolic Reprogramming and Lipophagy Mediates Survival of Ascites Derived Metastatic Ovarian Cancer Cells. (Pubmed Central) -  Jun 5, 2022   
     Metabolic reprogramming is a characteristic feature of the metastatic ovarian cancer cells that are persisting in the malignant ascites. Targeting of the metastatic by gaining an insight into the various metabolic and molecular changes that occur in the metastatic niche provides a promising therapeutic approach in management of the disease.
  • ||||||||||  pyrimethamine / Generic mfg., gefitinib / Generic mfg., atovaquone / Generic mfg.
    A Pharmacological Inhibitor Of Egfr Receptor And Antimicrobial Agents Cooperate To Enhance Protection Against Ocular And Cerebral Toxoplasmosis (Exhibit and Poster Hall) -  Jun 4, 2022 - Abstract #ASMMicrobe2022ASM_Microbe_3438;    
    B6 mice with pre-established ocular and cerebral toxoplasmosis treated with a low dose of Gefitinib and antimicrobial agent exhibited improved protection against ocular and cerebral toxoplasmosis. Overall, these data indicate that the combination of low doses of an EGFR TKI and antimicrobial agents cooperate to impair T. gondii-induced Akt activation resulting in potent toxoplasmacidal activity, and this combination regimen can improve treatment of ocular and cerebral toxoplasmosis in mice.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Interleukin-10 regulates starvation-induced autophagy through the STAT3-mTOR-p70s6k axis in hepatic stellate cells. (Pubmed Central) -  Jun 4, 2022   
    Cryptotanshinone (CPT) and rapamycin (Rapa) were used to block activation of the signal transducer and activator of transcription 3 (STAT3) and mTOR signaling pathways, respectively...Blocking either the mTOR or STAT3 pathway reversed the inhibitory effect of IL-10 on starvation-induced autophagy in HSC-T6 cells (p < 0.05). IL-10 suppresses starvation-induced autophagosome formation through activation of the STAT3-mTOR-p70s6k axis in HSC-T6 cells.
  • ||||||||||  SB202190 / Amgen, PD98059 / Wayne State University
    Journal:  Oxidative stress-induced autophagy compromises stem cell viability. (Pubmed Central) -  Jun 4, 2022   
    Further, autophagy inhibition by 3-Methyladenine (3-MA) significantly improved hDPSC viability. These findings contribute to a better understanding of post-transplantation hDPSC and hMSC death and may inform strategies to minimize therapeutic cell loss under oxidative stress.
  • ||||||||||  Journal:  Acetaldehyde Induces Cytotoxicity via Triggering Mitochondrial Dysfunction and Overactive Mitophagy. (Pubmed Central) -  Jun 4, 2022   
    Antioxidant N-acetyl-L-cysteine significantly attenuated the mitophagic responses and alleviated the cytotoxicity induced by acetaldehyde, indicating that oxidative stress was a major mediator of the excessive mitophagy induced by acetaldehyde. Taken together, these findings provided new insights into the role of mitophagy and oxidative stress in acetaldehyde-induced cytotoxicity.
  • ||||||||||  Journal:  Modulation of Ricin Intoxication by the Autophagy Inhibitor EACC. (Pubmed Central) -  Jun 4, 2022   
    Importantly, MRT68601 increased Golgi transport of ricin even in the presence of EACC, but EACC was still able to inhibit intoxication, supporting the idea that EACC protects at a late step along the retrograde pathway. These results also indicate that phosphorylation of syntaxin 17 is not required for the protection observed.
  • ||||||||||  Preclinical, Journal:  Effects of Zhongfeng capsule on autophagy related proteins expressions of brain tissue in rats with cerebral ischemia/reperfusion injury (Pubmed Central) -  Jun 4, 2022   
    The brain index, the gene and protein expressions of Beclin1 and LC3 were decreased apparently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01), while the expressions of p-PI3k and p-Akt in brain tissue were increased evidently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01). Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway.
  • ||||||||||  chloroquine phosphate / Generic mfg., sirolimus / Generic mfg.
    Journal:  Isoprenylated Coumarin Exhibits Anti-proliferative Effects in Pancreatic Cancer Cells Under Nutrient Starvation by Inhibiting Autophagy. (Pubmed Central) -  Jun 4, 2022   
    Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway. Our lead isoprenylated coumarin compound induces selective pancreatic cancer cell death under nutrient-deprived conditions through inhibition of autophagy, potentially providing insights into new therapeutic options.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Isoalantolactone Induces Cell Cycle Arrest, Apoptosis and Autophagy in Colorectal Cancer Cells. (Pubmed Central) -  Jun 4, 2022   
    Repression of autophagy with autophagy inhibitors chloroquine (CQ) and Bafilomycin A1 (Baf-A1) enhanced the anti-CRC effects of IATL, suggesting that IATL induces cytoprotective autophagy in CRC cells...Inhibition of AKT and mTOR activities using LY294002 and rapamycin, respectively, potentiated the inductive effects of IATL on autophagy and cell death...Collectively, our results demonstrated that in addition to inhibiting proliferation, inducing G0/G1-phase cell cycle arrest and apoptosis, IATL initiates cytoprotective autophagy in CRC cells by inhibiting the AKT/mTOR signaling pathway. These findings provide an experimental basis for the evaluation of IATL as a novel medication for CRC treatment.