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  • ||||||||||  Journal:  Deciphering the Effects and Mechanisms of Yi-Fei-San-Jie-pill on Non-Small Cell Lung Cancer With Integrating Network Target Analysis and Experimental Validation. (Pubmed Central) -  Jun 4, 2022   
    As a result, YFSJ markedly decreased tumor size and prolonged survival time in contrast with those in the orthotopic model group (p < 0.05), and it also significantly regulated the protein expression levels of apoptosis- and autophagy-related proteins. In conclusion, this study provides convincing evidence that YFSJ could inhibit the growth of tumors and prolong the survival time of tumor-bearing mice based on the NSCLC orthotopic model, and its anti-tumor effect was closely associated with the promotion of apoptosis and interference of autophagy coupled with regulation of immune infiltration.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB-P300-BRD4 axis. (Pubmed Central) -  Jun 4, 2022   
    Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.
  • ||||||||||  sirolimus / Generic mfg.
    Investigation Of The Divergent Roles Of Macrophage Mtor Signaling In Atherosclerosis (Grand Ballroom ABC) -  Jun 1, 2022 - Abstract #ATVBPVDGPM2022ATVB_PVD_GPM_467;    
    The mechanistic target of rapamycin (mTOR) pathway is considered a key regulator of cellular proliferation, survival, metabolism, and degradation...Interestingly, deletion of macrophage mTOR, which ablates both mTOR-dependent pathways leads to minimal change in plaques reflecting the apparently balanced and opposing roles of its signaling arms. Our data provide the first mechanistic details of macrophage mTOR signaling in atherosclerosis and suggest that therapeutic measures aimed at modulating mTOR need to account for its dichotomous functions.
  • ||||||||||  metformin / Generic mfg.
    Autophagy Is Differentially Regulated In Leukocyte And Nonleukocyte Foam Cells During Atherosclerosis (Grand Ballroom ABC) -  Jun 1, 2022 - Abstract #ATVBPVDGPM2022ATVB_PVD_GPM_180;    
    Our data therefore demonstrates a lack of functional autophagy in VSMC, as compared to MΦ foam cells, which impairs their ability to perform cholesterol efflux. This autophagy defect in VSMC foam cells can be increased by autophagy activation using metformin, highlighting both the importance of understanding cholesterol metabolism in all foam cell populations and a new avenue to treat atherosclerosis.
  • ||||||||||  5-fluorouracil / Generic mfg.
    Journal:  JAK2/STAT3 inhibitor reduced 5-FU resistance and autophagy through ATF6-mediated ER stress. (Pubmed Central) -  May 31, 2022   
    The mechanisms of action of JAK2/STAT3 pathway were investigated in AGS cells with drug resistance of 5-fluorouracil (5-FU) by corresponding inhibitors...Targeting JAK2/STAT3 pathway could be a potential approach to decrease the 5-FU resistance of gastric cancer and enhance the sensitivity of gastric cancer to 5-FU. Additionally, our study offers new insights into the molecular mechanisms underlying the resistance of gastric cancer to 5-FU.
  • ||||||||||  sirolimus / Generic mfg.
    Preclinical, Journal:  2-Mercaptoethanol promotes porcine oocyte maturation in vitro by maintaining autophagy homeostasis. (Pubmed Central) -  May 31, 2022   
    Interestingly, we observed that 44 h of coincubation with rapamycin/3-MA and 2-ME restored autophagy homeostasis in vitro. In conclusion, our study confirmed that 2-ME promotes porcine oocyte maturation and embryo development in vitro by maintaining autophagy homeostasis and lays a foundation for further research on the underlying mechanism.
  • ||||||||||  Review, Journal:  Hernandezine Regulates Proliferation and Autophagy-Induced Apoptosis in Melanoma Cells. (Pubmed Central) -  May 31, 2022   
    Combined with differential expression of P-AMPK, P-ACC (downstream targets of adenine monophosphate activated protein kinase, AMPK), and P-p70S6K (downstream targets of mammalian target of rapamycin, mTOR) and significant inhibition of apoptosis by AMPK inhibitor complex C (CC) in hernandezine-treated melanoma cells suggested that hernandezine could induce autophagy via the AMPK-mTOR pathway, thereby inducing apoptosis. This study first analyzed the effect of melanoma cells by hernandezine and provided a theory for hernandezine in the treatment of melanoma.
  • ||||||||||  doxorubicin hydrochloride / Generic mfg.
    Journal:  SERTAD1 Sensitizes Breast Cancer Cells to Doxorubicin and Promotes Lysosomal Protein Biosynthesis. (Pubmed Central) -  May 30, 2022   
    Simultaneously targeting cancer cells with Dox and autophagy inhibition successfully induced higher apoptosis/anoikis. The novel role of SERTAD1 in maintaining cellular homeostasis has also been suggested in which lysosomal contents, including LAMP1, LAMP2, CTSB, and CTSD, were reduced in SERTAD1-deficient cells.
  • ||||||||||  Review, Journal:  Repurposing Autophagy Regulators in Brain Tumors. (Pubmed Central) -  May 29, 2022   
    Sertraline and desipramine, depending on the neoplastic context, were demonstrated to either induce or inhibit autophagy. Collectively, these medications were associated with favorable therapeutic outcomes in a variety of cancer cell models, including brain tumors.
  • ||||||||||  bortezomib / Generic mfg.
    Journal:  Solamargine induces autophagy-mediated apoptosis and enhances bortezomib activity in multiple myeloma. (Pubmed Central) -  May 29, 2022   
    We also confirmed the single-agent efficacy of SM and the synergistic effects between SM and BTZ in an MM xenograft mouse model. Collectively, these findings indicate that SM exerts an anti-MM effect, at least in part, by activating cell autophagy and reveal that SM alone or in combination with BTZ is a potential therapeutic strategy for treating MM.
  • ||||||||||  Preclinical, Journal:  Patulin Induces Acute Kidney Injury in Mice through Autophagy-Ferroptosis Pathway. (Pubmed Central) -  May 29, 2022   
    Simultaneous autophagy-dependent ferroptosis can be inhibited by ferroptosis inhibitors ferrostatin-1 (Fer-1) and desferrioxamine (DFO). In general, this study provides a new perspective for exploring the new mechanism of acute kidney injury caused by PAT.
  • ||||||||||  Kinedak (epalrestat) / Ono Pharma
    Journal, IO biomarker:  Shabyar Ameliorates High Glucose Induced Retinal Pigment Epithelium Injury Through Suppressing Aldose Reductase and AMPK/mTOR/ULK1 Autophagy Pathway. (Pubmed Central) -  May 29, 2022   
    Human retinal pigment epithelial cells (ARPE-19) induced by high glucose was used as a model in vitro, with Epalrestat (EPL, AR inhibitor) and Difrarel (DFR, DR therapeutic drug) as positive controls...These data demonstrated that SBA treatment inhibits the autophagy of ARPE-19 through the AMPK/mTOR/ULK1 signaling pathway, and reduced early-stage apoptosis occurred by high glucose. These findings reveal the protective role and mechanism of SBA on retinal pigment epithelium, and provide experimental basis for the clinical application of SBA in the treatment of DR.
  • ||||||||||  Preclinical, Journal:  Cumulative autophagy insufficiency in mice leads to progression of β-cell failure. (Pubmed Central) -  May 27, 2022   
    Furthermore, we identified a novel gene, Sprr1a, which was expressed at more than 50-fold higher levels during both the 2-week and 6-week autophagy inhibition. These findings suggest that autophagy insufficiency cumulatively leads to β-cell failure after a certain interval, accompanied by stepwise alterations of gene expression patterns.
  • ||||||||||  Journal:  Overexpression of progranulin increases pathological protein accumulation by suppressing autophagic flux. (Pubmed Central) -  May 27, 2022   
    These results suggest that PGRN overexpression suppressed autophagic flux by inhibiting autophagosome-lysosome fusion. Moreover, PGRN overexpression enhanced polyglutamine aggregation and aggregate-prone TDP-43 accumulation, indicating that the suppression of autophagic flux by excessive amounts of PGRN worsens the pathology of neurodegenerative diseases.
  • ||||||||||  Journal:  Clionamines stimulate autophagy, inhibit Mycobacterium tuberculosis survival in macrophages, and target Pik1. (Pubmed Central) -  May 26, 2022   
    Chemical-genetic profiles of clionamines and cationic amphiphilic drugs (CADs) are closely related, linking the clionamine mode of action to co-localization with PI4P in a vesicular compartment. Small interfering RNA (siRNA) knockdown of PI4KB, a human homolog of Pik1, inhibited the survival of Mtb in macrophages, identifying PI4KB as an unexploited molecular target for efforts to develop HDT drugs for treatment of TB.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Apigenin alleviated PA-induced pyroptosis by activating autophagy in hepatocytes. (Pubmed Central) -  May 26, 2022   
    When the autophagy inhibitor chloroquine (CQ) was added, the data showed that the recovery effect of apigenin on PA-induced pyroptosis was weakened, indicating that apigenin could alleviate PA-induced pyroptosis by activating autophagy...On the one hand, apigenin eliminated damaged mitochondria by activating autophagy, thereby clearing reactive oxygen species (ROS) production and inhibiting the activation of the NLRP3 inflammasome, and on the other hand, activation of autophagy could directly degrade the NLRP3 inflammasome. Our study provides a new idea and target for the use of functional factors in food to alleviate liver injury.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Inhibitory Effect of Ursolic Acid on Proliferation and Migration of Renal Carcinoma Cells and Its Mechanism. (Pubmed Central) -  May 24, 2022   
    Further, AdPlus-mCherry-GFP-LC3B adenovirus transfection was used to detect the effect of ursolic acid on the autophagic flow of 786-O cells; ursolic acid was combined with the autophagy inhibitor chloroquine (CQ) to detect the expression level of autophagy protein LC3II by Western blot...Ursolic acid activated the autophagic flow in 786-O cells, as evidenced by the accumulation of autophagic fluorescent spots and enhanced fluorescence intensity of autophagosomes, and the combined use of the autophagy inhibitor CQ increased the expression level of LC3II compared to ursolic acid alone; ursolic acid decreased the expression levels of PTCH1, GLI1, SMO, SHH, and c-Myc and increased the expression level of Sufu in the hedgehog signaling pathway. Ursolic acid activates autophagy in renal carcinoma 786-O cells, probably by inhibiting hedgehog signaling pathway activity.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Survival of HT29 cancer cells is influenced by hepatocyte growth factor receptor inhibition through modulation of self-DNA-triggered TLR9-dependent autophagy response. (Pubmed Central) -  May 21, 2022   
    Lowest cell proliferation was achieved with the concomitant use of genomic DNA, HGFR inhibitor, and chloroquine, when the proliferation stimulating effect of STAT3 overexpression could be outweighed by the inhibitory effect of LC3B, indicating the putative involvement of HGFR-mTOR-ULK1 molecular cascade in HGFR inhibitor-mediated autophagy...The observed ultrastructural changes also support the context-dependent role of HGFR inhibition and autophagy on cell survival and proliferation. Further investigation of the influence of the studied signaling pathways and cellular processes can provide a basis for novel, individualized anti-cancer therapies.
  • ||||||||||  PACAP-Mediated Autophagy Prevents Liver Ischemia Reperfusion Injury in OLT (Board No. A055) -  May 20, 2022 - Abstract #ATC2022ATC_2054;    
    Our novel findings document the critical role of PACAP mediated autophagy in hepatic homeostasis and cytoprotection in liver IRI. Because the enhancement of hepatocellular autophagy differentially regulates local inflammation and hepatocyte survival, these results provide the rationale for emerging approaches to manage liver IRI in transplant patients.