- |||||||||| Review, Journal: Redox Regulation of Autophagy in Cancer: Mechanism, Prevention and Therapy. (Pubmed Central) - Jan 22, 2023
Notably, ROS can directly oxidize key autophagy proteins, such as ATG4 and p62, leading to the inhibition of autophagy pathway. In this review, we will elaborate the molecular mechanisms of redox regulation of autophagy in cancer, and discuss ROS- and autophagy-based therapeutic strategies for cancer treatment.
- |||||||||| Review, Journal: Targeting the Interplay of Autophagy and ROS for Cancer Therapy: An Updated Overview on Phytochemicals. (Pubmed Central) - Jan 22, 2023
In this review, we afford an overview of the complex regulatory relationship between autophagy and ROS in cancer, with an emphasis on phytochemicals that regulate ROS and autophagy for cancer therapy. We also discuss the effects of ROS/autophagy inhibitors on the anti-cancer effects of phytochemicals, and the challenges associated with harnessing the regulation potential on ROS and autophagy of phytochemicals for cancer therapy.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal: A Novel Tri-functional Liposome Re-educates "Cold Tumor" and Abrogates Tumor Growth by Synergizing Autophagy Inhibition and PD-L1 Blockade. (Pubmed Central) - Jan 20, 2023 In this study, a tri-functional doxorubicin (DOX) plus SAR405 liposome system was established and further modified with a novel anti-PD-L1 peptide JY4 for targeted delivery (DOX-SAR-JY4 )...As results, DOX-SAR-JY4 significantly inhibited tumor growth, metastasis and resurrection by re-educating immunosuppressive tumor microenvironment. In conclusion, our study not only proves the concept of inhibiting autophagy for better immune infiltration in the tumor but also presents a novel tri-functional liposomal system that overcomes the deficiencies of current therapies and holds great promise in cancer immunotherapy.
- |||||||||| Review, Journal: The role of autophagy in viral infections. (Pubmed Central) - Jan 20, 2023
Interestingly, different viruses have unique strategies to counteract different types of selective autophagy, such as exploiting autophagy to regulate organelle degradation, metabolic processes, and immune responses. In short, this review focuses on the interaction between autophagy and viruses, explaining how autophagy serves multiple roles in viral infection, with either proviral or antiviral functions.
- |||||||||| Journal: Myo1b Promotes Premature Endothelial Senescence and Dysfunction via Suppressing Autophagy: Implications for Vascular Aging. (Pubmed Central) - Jan 20, 2023
In vitro and in vivo aging models, Myo1b knockdown in senescent ECs and wild type-aged mice is able to enhance autophagy and ameliorate aging-associated endothelial dysfunction. Taken together, our studies reveal a new function for Myo1b, that is, to couple LRRK2 assembly to promote an increase in intracellular calcium level, which impairs the autophagosome-lysosome fusion, and ultimately the promotion of EC senescence and vascular aging.
- |||||||||| Copiktra (duvelisib) / Secura Bio, Yakult Honsha
Journal: Duvelisib attenuates bleomycin-induced pulmonary fibrosis via inhibiting the PI3K/Akt/mTOR signalling pathway. (Pubmed Central) - Jan 19, 2023 In vitro and in vivo pharmacological experiments showed that Duvelisib dose-dependently suppressed lung fibroblast activation and improved autophagy inhibition by inhibiting the phosphorylation of PI3K, Akt and mTOR. Our results indicate that Duvelisib can alleviate the severity of pulmonary fibrosis and provide potential drugs for the treatment of pulmonary fibrosis.
- |||||||||| sirolimus / Generic mfg.
Journal: Inhibition of autophagy in microglia and macrophages exacerbates innate immune responses and worsens brain injury outcomes. (Pubmed Central) - Jan 19, 2023 Conversely, increasing autophagy by treatment with rapamycin decreased inflammation and improved outcomes in wild-type mice after TBI. Overall, our work demonstrates that inhibition of autophagy in microglia and infiltrating macrophages contributes to excessive neuroinflammation following brain injury and in the long term may prevent resolution of inflammation and tissue regeneration.Abbreviations: Becn1/BECN1, beclin 1, autophagy related; CCI, controlled cortical impact; Cybb/CYBB/NOX2: cytochrome b-245, beta polypeptide; DAMP, danger/damage-associated molecular patterns; Il1b/IL1B/Il-1β, interleukin 1 beta; LAP, LC3-associated phagocytosis; Map1lc3b/MAP1LC3/LC3, microtubule-associated protein 1 light chain 3 beta; Mefv/MEFV/TRIM20: Mediterranean fever; Nos2/NOS2/iNOS: nitric oxide synthase 2, inducible; Nlrp3/NLRP3, NLR family, pyrin domain containing 3; Sqstm1/SQSTM1/p62, sequestosome 1; TBI, traumatic brain injury; Tnf/TNF/TNF-α, tumor necrosis factor; Ulk1/ULK1, unc-51 like kinase 1.
- |||||||||| Journal: ULK1-mediated phosphorylation regulates the conserved role of YKT6 in autophagy. (Pubmed Central) - Jan 17, 2023
Moreover, mammalian autophagosomal YKT6 is phospho-regulated by the ULK1 kinase, preventing premature bundling with the lysosomal SNARE proteins and thereby inhibiting autophagosome-lysosome fusion. Together, our findings reveal that timely regulation of the YKT6 phosphorylation status is crucial throughout autophagy progression and cell survival.
- |||||||||| Journal: Slingshot homolog-1 amplifies mitochondrial abnormalities by distinctly impairing health and clearance of mitochondria. (Pubmed Central) - Jan 14, 2023
Our results indicate that SSH1 suppresses mitochondrial health and respiration through the cofilin-binding N-terminal region, whereas SSH1 impairs mitophagy through a newly identified ~ 100 residue p62-binding domain in the C-terminal region. These results indicate that both N-terminal and C-terminal regions negatively impact mitochondria by distinct and independent modalities to amplify mitochondrial abnormalities, making SSH1 an excellent target to mitigate ad pathogenesis.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal: Protective Role of Cezanne in Doxorubicin-induced Cardiotoxicity by inhibiting Autophagy, Apoptosis and Oxidative Stress. (Pubmed Central) - Jan 14, 2023 Mechanistically, the overexpression of Cezanne significantly reversed the in-activation of the PI3K/AKT/mTOR pathway induced by DOX, while the inhibitors of this pathway abolished the effect of Cezanne, suggesting that the PI3K/AKT/mTOR pathway plays a role in the protective function of Cezanne. These findings indicate that Cezanne could ameliorate DOX-induced cardiotoxicity by attenuating the apoptosis and autophagy of cardiomyocytes and decreasing the level of oxidative stress.
- |||||||||| Journal: Betulinaldehyde exhibits effective anti-tumor effects in A549 cells by regulating intracellular autophagy. (Pubmed Central) - Jan 14, 2023
The pretreatment of A549 cells with the autophagy inhibitor, 3-methyladenine, could partially negate the anti-tumor effects of betulinaldehyde. These findings suggest that betulinaldehyde could significantly inhibit the oncological activity of A549 cells by regulating the intracellular autophagy level, making it a potentially effective option for the adjuvant therapy used to treat lung cancer in the future.
- |||||||||| chloroquine phosphate / Generic mfg., sirolimus / Generic mfg.
Calcitonin receptor expression in stressed and autophagic cells an event identified with a novel imaging reagent on the high throughput screening platform operetta () - Jan 13, 2023 - Abstract #LCC2023LCC_236; Much contemporary cancer research focuses on drug discovery such as rapamycin mimetics that induce autophagy in cancer cells and have been tested in clinical trials (1)...Futher, treatment with inhibitors of autophagy, chloroquine that inhibits fusion of autophagosomes with lysosomes or 3-methyladenine which inhibits formation of the essential factor IP3 (via IP3 kinase) in elongation, inhibited the increased fluorescence intensity associated with autophagy...A novel ligand of calcitonin receptor reveals a potential new sensor that modulates programmed cell death. Cell Death Disc 2:16062, 2016.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis, BeiGene
Trial completion date, Trial primary completion date: A Trial of Dabrafenib, Trametinib and Hydroxychloroquine for Patients With Recurrent LGG or HGG With a BRAF Aberration (clinicaltrials.gov) - Jan 11, 2023 P1/2, N=75, Recruiting, Conclusion VD can inhibit PM-induced autophagy and cytokine release in A549 cells, thus playing a protective role. Trial completion date: Feb 2027 --> Jun 2027 | Trial primary completion date: Feb 2025 --> Aug 2025
- |||||||||| Preclinical, Journal: FGF10 ameliorates lipopolysaccharide-induced acute lung injury in mice via the BMP4-autophagy pathway. (Pubmed Central) - Jan 10, 2023
Additionally, the inhibition of autophagy by 3-MA also lowered the protective effect of FGF10 on alveolar epithelial cells induced by LPS. These data suggest that the protective effect of FGF10 is related to the activation of autophagy and regeneration of alveolar epithelial cells in an LPS-induced ALI model, and that the activation of autophagy may depend on the increase in BMP4 expression.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Protective Effect of Phloretin against Hydrogen Peroxide-Induced Oxidative Damage by Enhancing Autophagic Flux in DF-1 Cells. (Pubmed Central) - Jan 10, 2023 Importantly, autophagy inhibitor chloroquine (CQ) reversed the protective effect of PHL, and increased HO-induced apoptosis...Collectively, these results indicate that PHL could attenuate HO-induced oxidative injury and apoptosis by maintaining lysosomal function and promoting autophagic flux, and MAPKs pathway may be involved in this process. Our study provides evidence that PHL could as a new strategy to against oxidative damage in poultry industry.
- |||||||||| LY294002 / Eli Lilly, AG1478 / IDT Australia
Journal: Cryptosporidium parvum maintains intracellular survival by activating the host cellular EGFR-PI3K/Akt signaling pathway. (Pubmed Central) - Jan 10, 2023 The EGFR inhibitor AG1478 decreased EGFR and Akt phosphorylation, and the PI3K inhibitor LY294002 impaired Akt phosphorylation induced by C. parvum in HCT-8 cells...Intracellular parasite proliferation was decreased when treated with autophagy inducer rapamycin, whereas autophagy inhibitor 3-MA, E64d+pep A, siBeclin1 or siATG7 increased intracellular parasites...In summary, C. parvum could maintain intracellular survival by inhibiting autophagy via EGFR-PI3K/Akt pathway. These results revealed a new mechanism for the interaction of C. parvum with host cells.
- |||||||||| dorsomorphin (Compound C) / EMD Serono
Journal: Ferroptosis is involved in PM2.5-induced acute nasal epithelial injury via AMPK-mediated autophagy. (Pubmed Central) - Jan 8, 2023 Treatment with the ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (Fer-1) significantly reversed the toxicity of PM2.5 to human nasal epithelial cells (HNEPCs)...In addition, CC greatly inhibited autophagy activation but reversed the downregulation of GPX4 and FTH1 induced by PM2.5 in the nasal epithelium of mice. Together, these data suggest that AMPK-mediated autophagy plays an important role in PM2.5-induced ferroptosis and that AMPK might be a potential treatment target for PM2.5-induced nasal epithelial injury.
|