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  • ||||||||||  Low EV miR-30c Levels as Biomarker of Increased Tumor Autophagy and Chemoradiotherapy Resistance in Locally Advanced NSCLC (Exhibit Hall - Hall B) -  Jun 24, 2022 - Abstract #IASLCWCLC2022IASLC_WCLC_1896;    
    This study describes, for the first time, that EV-miRNAs, in particular miR-30c, are involved in the regulation of autophagy as a mechanism of resistance to chemoradiotherapy observed also by the presence of autophagic-CTCs. Thus, we promising propose the use of EV miR-30c and autophagic CTCs as biomarkers for the stratification and monitoring of stage III NSCLC patients undergoing chemoradiation, who could also potentially benefit from novel combinatorial therapies with autophagy inhibitors.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Autophagy inhibition by TSSC4 (tumor suppressing subtransferable candidate 4) contributes to sustainable cancer cell growth. (Pubmed Central) -  Jun 22, 2022   
    Finally, TSSC4 suppresses tumorsphere formation and tumor growth by inhibiting autophagy and maintaining cell survival in tumorspheres. Taken together, sustainable cancer cell growth can be achieved by autophagy inhibition via TSSC4 expression.ABBREVIATIONS: 3-MA: 3-methyladenine; ACTB: actin beta; CQ: chloroquine; EGFRvIII: epidermal growth factor receptor variant III; ERBB2: erb-b2 receptor tyrosine kinase 2; GBM: glioblastoma multiforme; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule Associated protein 1 light chain 3; TSSC4: tumor suppressing subtransferable candidate 4.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  mA reader YTHDC1 modulates autophagy by targeting SQSTM1 in diabetic skin. (Pubmed Central) -  Jun 22, 2022   
    Furthermore, the results revealed that YTHDC1 interacted and cooperated with ELAVL1/HuR (ELAV like RNA binding protein 1) in modulating the expression of SQSTM1. Collectively, this study uncovered a previously unrecognized function for YTHDC1 in modulating autophagy via regulating the stability of SQSTM1 nuclear mRNA in diabetic keratinocytes.Abbreviations: ACTB: actin beta; AGEs: glycation end products; AL: autolysosome; AP: autophagosome; ATG: autophagy related; AKT: AKT serine/threonine kinase; ANOVA: analysis of variance; BECN1: beclin 1; Co-IP: co-immunoprecipitation; DEGs: differentially expressed genes; DM: diabetes mellitus; ELAVL1: ELAV like RNA binding protein 1; FTO: FTO alpha-ketoglutarate dependent dioxygenase; G: glucose; HaCaT: human keratinocyte; GO: Gene Ontology; GSEA: Gene Set Enrichment Analysis; HE: hematoxylin-eosin; IHC: immunohistochemical; IRS: immunoreactive score; KEAP1: kelch like ECH associated protein 1; KEGG: Kyoto Encyclopedia of Genes and Genomes; mA: N-methyladenosine; M: mannitol; MANOVA: multivariate analysis of variance; MAP1LC3: microtubule associated protein 1 light chain 3; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MeRIP: methylated RNA immunoprecipitation; METTL3: methyltransferase 3, N6-adenosine-methytransferase complex catalytic subunit; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin complex 1; NBR1: NBR1 autophagy cargo receptor; NFE2L2: nuclear factor, erythroid 2 like 2; NG: normal glucose; NHEK: normal human epithelial keratinocyte; OE: overexpressing; p-: phospho-; PI: propidium iodide; PPIN: Protein-Protein Interaction Network; RBPs: RNA binding proteins; RIP: RNA immunoprecipitation; RNA-seq: RNA-sequence; RNU6-1: RNA, U6 small nuclear 1; ROS: reactive oxygen species; siRNAs: small interfering RNAs; SQSTM1: sequestosome 1; SRSF: serine and arginine rich splicing factor; T2DM: type 2 diabetes mellitus; TEM: transmission electron microscopy; TUBB: tubulin beta class I; WT: wild-type; YTHDC1: YTH domain containing 1.
  • ||||||||||  Mekinist (trametinib) / Novartis, Tafinlar (dabrafenib) / Novartis
    Journal, IO biomarker:  Clinical trial results show promise of targeting autophagy BRAF mutant melanoma. (Pubmed Central) -  Jun 22, 2022   
    Progression-free survival does not meet the pre-specified threshold for the entire cohort but looks especially promising in patients with elevated LDH and prior treatment. A national randomized study has been launched to study this regimen further in poor-prognosis BRAF V600-mutant melanoma patients.
  • ||||||||||  Journal:  MTOR-mediates hepatic lipid metabolism through an autophagic SNARE complex. (Pubmed Central) -  Jun 22, 2022   
    VAMP8 phosphorylation can disrupt autophagosome-lysosome fusion in the liver and thereby dysregulate lipid metabolism. Beyond providing insights into the molecular mechanisms of autophagosome maturation, our study suggests that modulating autophagic SNARE function may help treat liver lipid disorders.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Inhibition of Drp1 ameliorates diabetic retinopathy by regulating mitochondrial homeostasis. (Pubmed Central) -  Jun 22, 2022   
    In vivo, we found that intraretinal microvascular abnormalities (IRMA), including retinal vascular leakage, acellular capillaries, and apoptosis were increased in STZ-induced DR rats, which were reversed by pretreatment with Mdivi-1 or Rapamycin. Altogether, our findings provide new insight into the mechanisms underlying the regulation of mitochondrial homeostasis and provide a potential treatment strategy for Diabetic retinopathy.
  • ||||||||||  Journal, IO biomarker:  BCG therapy downregulates HLA-I on malignant cells to subvert antitumor immune responses in bladder cancer. (Pubmed Central) -  Jun 22, 2022   
    We surmise that HLA-I expression in bladder cancers at relapse post-BCG does not result from immunoediting but rather from an immune subversion process directly induced by BCG on cancer cells, which predicts dismal prognosis. Cancer cells HLA-I scoring by immunohistochemistry (IHC) staining can be easily implemented by pathologists in routine practice in order to stratify future urothelial cancer patient treatment strategies.
  • ||||||||||  Journal:  Melatonin Alleviates Liver Fibrosis by Inhibiting Autophagy. (Pubmed Central) -  Jun 22, 2022   
    Autophagy inhibition is a potential therapeutic strategy for alleviating the placental toxicity of nanoparticles. Melatonin might ameliorate liver fibrosis by regulating autophagy, suggesting that melatonin is a potential therapeutic agent for liver fibrosis.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  New sight into interaction between endoplasmic reticulum stress and autophagy induced by vanadium in duck renal tubule epithelial cells. (Pubmed Central) -  Jun 22, 2022   
    Duck renal tubule epithelial cells were exposed to different concentrations of sodium metavanadate (NaVO) (0, 100 and 200 μM) and PERK inhibitor (GSK, 1 μM), or autophagy inhibitor (chloroquine, 50 μM) alone for 24 h (chloroquine for the last 4 h)...Together, our data suggested that excessive V could induce ER stress and autophagy in duck renal tubular epithelial cells. ER stress might promote V-induced autophagy via the PERK/ATF4/CHOP signaling pathway, and autophagy may play a role in alleviating ER stress induced by V.
  • ||||||||||  sevoflurane / Generic mfg.
    Journal:  Activation of the AMPK-ULK1 pathway mediated protective autophagy by sevoflurane anesthesia restrains LPS-induced acute lung injury (ALI). (Pubmed Central) -  Jun 22, 2022   
    At the same time current study will help in characterizing the underlying cellular processes that may play a role in escaping tutor suppressor role CMA and macroautophagy in cancers harboring K-Ras G12V mutation that may be further utilized to identify molecular targets for K-Ras-driven cancers. Collectively, sevoflurane suppresses apoptosis and inflammation via activating protective autophagy, thereby ameliorating LPS-induced ALI, and the AMPK/ULK1/ PIKFYVE pathway is responsible for the process.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Autophagy regulates transforming growth factor β signaling and receptor trafficking. (Pubmed Central) -  Jun 22, 2022   
    We impaired autophagy in non-small cell lung cancer cells using chloroquine, spautin-1, ULK-101, or small interfering RNA (siRNA) targeting autophagy-related gene (ATG)5 and ATG7 and observed that inhibiting autophagy results in a decrease in TGFβ1-dependent EMT transcription factor and cell marker expression, as well as attenuated stress fiber formation and cell migration...We observed that inhibiting autophagy decreased the amount and timeframe of Smad2/Smad3 signaling. Taken together, our results suggest that inhibiting autophagy attenuates pro-tumorigenic TGFβ signaling by regulating receptor trafficking, resulting in impaired Smad2/Smad3 phosphorylation and nuclear accumulation.
  • ||||||||||  LY294002 / Eli Lilly, dactolisib (RTB101) / Adicet Bio
    Journal:  Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma. (Pubmed Central) -  Jun 22, 2022   
    When combined with various autophagy inhibitors, along with siRNA against ATG7, NVP-BEZ235 showed a synergic antitumor effect in LSCC through increasing cell apoptosis and death both in vitro and vivo. NVP-BEZ235 exerted potent antitumor effects on LSCC, especially when combined with the autophagy inhibitor both in vitro and vivo, providing convincing experimental data for new molecular targeted therapy for LSCC.
  • ||||||||||  SB202190 / Amgen
    Journal, PARP Biomarker:  Carnosol Induces p38-Mediated ER Stress Response and Autophagy in Human Breast Cancer Cells. (Pubmed Central) -  Jun 22, 2022   
    Interestingly, inhibition of p38MAPK, by SB202190 and 203580, reduced cell death, selectively blocked the induction of IRE-1α and ATF6 UPR sensors and inhibited autophagy...Importantly, activation of PERK sensors and induction of apoptosis occurred independently of p38 activation. Taken together, our results suggest that ROS-dependent induced-ER stress contributes to carnosol-induced apoptotic and autophagic cell death in breast cancer cells, and further confirm that carnosol is a promising agent for breast cancer therapy.
  • ||||||||||  donepezil / Generic mfg.
    Preclinical, Journal:  Galangin alleviates learning and memory impairments in APP/PS1 double- transgenic mice by regulating Akt/MEF2D/Beclin-1 signaling pathway (Pubmed Central) -  Jun 22, 2022   
    Compared with the model group, donepezil and galangin shortened the swimming time, reduced the number of errors and electric shocks, down-regulated the expression of p-tau, Aβ_(42), APP, AChE, BACE1, GFAP, and Beclin-1, prolonged the incubation period, up-regulated p-Akt and MEF2 D, and improved the pathological changes in hippocampus. Compared with the autophagy inhibitor group, galangin prolonged the swimming time, elevated the number of errors and electric shocks, enhanced the expression of p-tau, Aβ_(42), APP, AChE, BACE1, GFAP, and Beclin-1, shortened the incubation period, and diminished the expression of p-Akt and MEF2 D. In conclusion, galangin improves the learning and memory impairments and hippocampal neuron injury of APP/PS1 mice, which may be related to its regulation of Akt/MEF2 D/Beclin-1 signaling pathway.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Apigenin ameliorates hepatic lipid accumulation by activating the autophagy-mitochondria pathway. (Pubmed Central) -  Jun 21, 2022   
    Inhibition of autophagy by bafilomycin A1 or chloroquine abolished the protection of apigenin in OA-induced lipid accumulation...Moreover, apigenin increased the mitochondrial network structure and mitochondrial function by increasing the protein expression related to the process of mitochondria fusion and mitochondrial function. Collectively, our findings suggest that apigenin ameliorates hepatic lipid accumulation by activating the autophagy-mitochondrial pathway.
  • ||||||||||  Journal:  MYC drives autophagy to adapt to stress in Penaeus vannamei. (Pubmed Central) -  Jun 19, 2022   
    In addition, the Total hemocyte count (THC) decreased sharply, and accelerated the injury of hepatopancreas under low temperature stress after silencing PvMYC. Collectively, these results suggest that PvMYC has vital role in the cold adaptation mechanism of P. vannamei by negatively regulating autophagy.
  • ||||||||||  Preclinical, Journal:  The role of TNF-α/TNFR1 inhibiting autophagy of M1-type Kupffer cells in liver injury in trichloroethylene-sensitized mice (Pubmed Central) -  Jun 19, 2022   
    Immunofluorescence results showed that the iNOS protein levels in the blank control group, solvent control group and TCE non-sensitized group were lower, and only partially colocalized with P62; the colocalization of iNOS with P62 in the TCE sensitized group was significantly increased. TNF-α/TNFR1 signaling pathway may promote liver injury in TCE-sensitized mice by inhibiting autophagy of M1-type Kupffer cells.
  • ||||||||||  Journal:  Emerging roles of mitotic autophagy. (Pubmed Central) -  Jun 19, 2022   
    Because the involvement of autophagy in mitosis remains controversial, it is important to consider the specific contribution of signalling cascades, the functions of autophagic proteins and the multiple roles of lysosomes, as three entangled, but independent, factors controlling genomic stability. In this Review, we discuss the latest advances in this area and highlight the therapeutic potential of targeting autophagy for drug development.
  • ||||||||||  Jardiance (empagliflozin) / Eli Lilly, Boehringer Ingelheim
    Empagliflozin alleviates diabetic cardiomyopathy via inhibiting excessive autophagy and adverse remodeling in type 1 diabetic mice (Research Gateway 10) -  Jun 15, 2022 - Abstract #ESC2022ESC_3386;    
    Our results indicate that EMPA plays a cardioprotective effect by inhibiting excessive autophagy through the mTOR/AMPK axis in the mouse model of STZ-induced type 1 diabetes. EMPA also promotes cardiac reverse remodeling by inhibiting fibrosis, activates cardiac Cx43 and the promyogenic transcriptional program through the sirtuins-SRF axis (Figure), in the context of diabetes.
  • ||||||||||  hydroxychloroquine / Generic mfg.
    Journal:  Increased alveolar epithelial TRAF6 via autophagy-dependent TRIM37 degradation mediates particulate matter-induced lung metastasis. (Pubmed Central) -  Jun 14, 2022   
    Importantly, ROS blockade, autophagy inhibition or TRAF6 knockdown abolished PM-induced neutrophil recruitment and lung metastasis enhancement. Our study indicates that host lung epithelial cells and neutrophils coordinate to promote cancer metastasis to the lungs in response to PM exposure and provides ideal therapeutic targets for metastatic progression.Abbreviations: ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ATII: alveolar type II; Cho-Traf6 siRNA: 5'-cholesterol-Traf6 siRNA; EMT: epithelial-mesenchymal transition; HBE: human bronchial epithelial; HCQ: hydroxychloroquine; MAPK: mitogen-activated protein kinase; NAC: N-acetyl-L-cysteine; NFKB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NS: normal saline; PM: particulate matter; ROS: reactive oxygen species; TRAF6: TNF receptor-associated factor 6; TRIM37: tripartite motif-containing 37.
  • ||||||||||  metformin / Generic mfg.
    Journal:  SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1. (Pubmed Central) -  Jun 11, 2022   
    Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D, metformin or polydatin abrogated NSP6-induced pyroptosis...Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.