- |||||||||| Journal: Dysfunction of ATG7-dependent autophagy dysregulates the antioxidant response and contributes to oxidative stress-induced biological impairments in human epidermal melanocytes. (Pubmed Central) - Feb 11, 2021
Notably, we verified that ATG7-dependent autophagy could alter oxidative stress homeostasis by regulating reactive oxygen species (ROS) production, nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, and the activity of several antioxidant enzymes in melanocytes. In conclusion, our study suggested that ATG7-dependent autophagy is indispensable for redox homeostasis and the biological functions of melanocytes, such as melanogenesis, proliferation, apoptosis, and senescence, especially under oxidative stress.
- |||||||||| erastin - Whitehead Institute for Biomedical Research, Dana / Farber Cancer Institute, Columbia University, Prolexys, Nexavar (sorafenib) / Bayer, Amgen
Journal: Circular RNA cIARS regulates ferroptosis in HCC cells through interacting with RNA binding protein ALKBH5. (Pubmed Central) - Feb 11, 2021 Small interfering RNA against cIARS (si-cIARS) significantly suppressed the cellular sensitivity to SF or Erastin through inactivating ferroptosis, which may be partially attributed to the inhibition of autophagy and ferritinophagy...Furthermore, the inhibition of ferroptotic events, autophagic flux and ferritinophagy resulted from si-cIARS, were significantly rescued by ALKBH5 downregulation. Overall, cIARS may be an important circRNA, positively regulating SF-induced ferroptosis through suppressing the ALKBH5-mediated autophagy inhibition.
- |||||||||| paclitaxel / Generic mfg.
Journal: Ferroptosis: a novel mechanism of artemisinin and its derivatives in cancer therapy. (Pubmed Central) - Feb 10, 2021 Artemisinin and its derivatives could be used in the future as cancer therapies with broader applications due to their induction of ferroptosis. Meanwhile, more attention should be paid to the development of novel artemisinin-related drugs based on the mechanism of artemisinininduced ferroptosis.
- |||||||||| Journal, IO biomarker: Toll-Like Receptor 2-Mediated Autophagy Promotes Microglial Cell Death by Modulating the Microglial M1/M2 Phenotype. (Pubmed Central) - Feb 9, 2021
Collectively, our study demonstrates that the inhibition of autophagy or the absence of TLR2 induces microglial polarization towards the M2 phenotype, promotes microglial survival alone, and alleviates the development of neuroinflammation. In summary, TLR2-mediated autophagic signaling contributes to regulating the inflammatory response to activate microglial M1/M2 switching, which affects microglial survival after infection.
- |||||||||| cisplatin / Generic mfg.
Journal: Inhibition of autophagy improves resistance and enhances sensitivity of gastric cancer cells to cisplatin. (Pubmed Central) - Feb 9, 2021 Then, we discovered that inhibiting autophagy by chloroquine (CQ) significantly enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP to SGC-7901 and SGC-7901/DDP cells...However, the autophagy inducer everolimus (RAD001) had no obvious effects on the sensitivity of gastric cells to DDP...Additionally, we found interfering Beclin-1using Beclin-1-shRNA also enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP on gastric cancer cells by inhibiting phosphorylation of Akt. Our study exposures that inhibiting autophagy could improve the chemoresistance and enhanced sensitivity of gastric cancer cells to DDP and provides a rationale that the administration of cisplatin combined with CQ for treating patients with gastric cancer.
- |||||||||| Preclinical, Journal: Ferroptosis is involved in alcohol-induced cell death in vivo and in vitro. (Pubmed Central) - Feb 9, 2021
Importantly, ferrostatin-1 significantly ameliorated liver injury that was induced by overdosed alcohol both in vitro and in vivo. These findings highlight that targeting ferroptosis serves as a hepatoprotective strategy for alcoholic liver disease treatment.
- |||||||||| Journal: Protein Kinase R Restricts the Intracellular Survival of Mycobacterium tuberculosis by Promoting Selective Autophagy. (Pubmed Central) - Feb 9, 2021
Consistent with this mechanism, inhibition of autophagolysosome maturation with bafilomycin A1 abrogated the ability of THP-PKR macrophages to limit replication of Mtb, whereas pharmacological activation of autophagy enhanced the anti-mycobacterial effect of PKR overexpression. As such, PKR represents a novel and attractive host target for development of HDT for TB, and our data suggest value in the design of more specific and potent activators of PKR.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal, IO biomarker: Effect of Oleanolic Acid on Apoptosis and Autophagy of SMMC-7721 Hepatoma Cells. (Pubmed Central) - Feb 7, 2021 MATERIAL AND METHODS SMMC-7721 cells (a hepatocellular carcinoma cell line) were treated with different concentrations of oleanolic acid (OA) plus autophagy inhibitor 3-methyladenine (3-MA) (3-MA+OA) or chloroquine (CQ) plus OA (CQ+OA)...This suggested that OA activated autophagy of SMMC-7721 cells in a protective autophagic manner. CONCLUSIONS The study findings suggest that OA combined with autophagy inhibitor 3-MA can better exert its anticancer effect.
- |||||||||| sirolimus / Generic mfg.
Journal: Mutual regulation of ROS accumulation and cell autophagy in wheat roots under hypoxia stress. (Pubmed Central) - Feb 7, 2021 In conclusion, hypoxia stress induced ROS accumulation in wheat roots where ROS acted as an autophagy signal. Furthermore, higher levels of autophagy and antioxidant enzyme expression in the stele facilitated the elimination of oxidative damage caused by excessive ROS and thereby increased cell survival; in the cortex, a large number of cells died and formed aerenchyma.
- |||||||||| Preclinical, Journal: Luteolin attenuates sepsis‑induced myocardial injury by enhancing autophagy in mice. (Pubmed Central) - Feb 5, 2021
The protective effect of luteolin was abolished by 3‑methyladenine (an autophagy inhibitor) and dorsomorphin (compound C, an AMPK inhibitor), as evidenced by decreased autophagic activity, destabilized mitochondrial membrane potential and increased apoptosis in LPS‑treated cardiomyocytes, but was mimicked by 5‑aminoimidazole‑4‑carboxamide ribonucleotide (an AMPK activator), suggesting that luteolin attenuates LPS‑induced myocardial injury by increasing autophagy through AMPK activation. Luteolin may be a promising therapeutic agent for treating SIC.
- |||||||||| Journal: Blockage of protease-activated receptor 2 exacerbates inflammation in high-fat environment partly through autophagy inhibition. (Pubmed Central) - Feb 4, 2021
Reduced cell viability and greater induction of apoptosis, as shown by increased levels of cleaved caspase-9, cleaved caspase-3, and cleaved PARP, were observed in cells treated with GB83, PA, and CC but not in those treated with only PA and CC. Collectively, protective effects of PAR2 were elucidated during inflammation accompanied by high-fat environment by promoting autophagy and inhibiting apoptosis, suggesting PAR2 as a therapeutic target for inflammatory bowel disease co-occurring with metabolic syndrome.
- |||||||||| tamoxifen / Generic mfg.
[VIRTUAL] The Role of Antisense RNA in Gene Expression After Treatment with Autophagy Modulators () - Feb 3, 2021 - Abstract #AAAAI2021AAAAI_1058; However, the antiRNA for the inflammatory gene PYCARD did not affect gene expression regardless of treatment. We found that many of these direct relationships remained. Conclusions Further gene expression studies which will include other RNA species will be needed to discover all determinants of mRNA expression in the presence of TX or CQ.
- |||||||||| cisplatin / Generic mfg., sirolimus / Generic mfg.
Journal: miR-21 modulates cisplatin resistance of gastric cancer cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway. (Pubmed Central) - Feb 3, 2021 Transfection of GC cells with miR-21 mimics contributed to restored DDP resistance by suppressing autophagy, while miR-21 inhibitor sensitized DDP-resistant GC cells by promoting autophagy. In conclusion, the results demonstrated that miR-21 is associated with DDP resistance in GC cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway, and autophagy inducers could be therapeutic targets for the effective treatment of DDP resistance in GC.
- |||||||||| Journal: ULK1 inhibition as a targeted therapeutic strategy for FLT3-ITD-mutated acute myeloid leukemia. (Pubmed Central) - Feb 3, 2021
In conclusion, the results demonstrated that miR-21 is associated with DDP resistance in GC cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway, and autophagy inducers could be therapeutic targets for the effective treatment of DDP resistance in GC. ULK1 is a viable drug target and ULK1 inhibition may represent a promising therapeutic strategy against FLT3-ITD AML.
- |||||||||| cisplatin / Generic mfg.
Journal: Mechanism of autophagy regulating chemoresistance in esophageal cancer cells. (Pubmed Central) - Feb 3, 2021 The autophagy was induced by cisplatin in human esophageal cancer EC9706 cells line...The expression level of autophagy-related proteins was also detected by Western blotting. Our findings indicated that autophagy may be a self-protective mechanism of esophageal cancer cells induced by DDP, and its inhibition may be a new strategy for adjuvant chemotherapy in esophageal cancer.
- |||||||||| sirolimus / Generic mfg.
Journal: Autophagy of periodontal ligament inhibits inflammation and reduces the decline of bone density during orthodontic tooth movement of mice. (Pubmed Central) - Feb 3, 2021 Our findings indicated that autophagy may be a self-protective mechanism of esophageal cancer cells induced by DDP, and its inhibition may be a new strategy for adjuvant chemotherapy in esophageal cancer. The increase of autophagy can reduce the decline of bone density, inhibit the expression of inflammatory factors, and arrange the periodontal ligament during OTM, thus providing a new way for the effective regulation of inflammation in clinical orthodontic treatment, so as to achieve more efficient and healthier tooth movement.
- |||||||||| sirolimus / Generic mfg.
Journal: Autophagy inhibition attenuates TGF-β2-induced epithelial-mesenchymal transition in lens epithelial cells. (Pubmed Central) - Feb 3, 2021 The increase of autophagy can reduce the decline of bone density, inhibit the expression of inflammatory factors, and arrange the periodontal ligament during OTM, thus providing a new way for the effective regulation of inflammation in clinical orthodontic treatment, so as to achieve more efficient and healthier tooth movement. Intervention/inhibition of autophagy could attenuate TGF-β2-induced EMT in LECs, which provides autophagy-related insights on preventing and treating the fibrotic cataract or other fibrotic diseases.
- |||||||||| Review, Journal: Inhibiting autophagy to prevent drug resistance and improve anti-tumor therapy. (Pubmed Central) - Feb 3, 2021
In this review, we overviewed the pathways and molecular aspects of autophagy, its role in carcinogenesis, and the evidence for its role in cancer adaptation and drug-resistance. Finally, we reviewed the clinical findings on how the autophagy interference helps to improve conventional anticancer therapy.
- |||||||||| Ixempra (ixabepilone) - Otsuka, R / Pharm, Allarity Therap
Journal, IO biomarker: A multi-scale systems pharmacology approach uncovers the anti-cancer molecular mechanism of Ixabepilone. (Pubmed Central) - Feb 2, 2021 In addition, Ixabepilone also decreases Bcl-2 protein expression and induces cytoprotective autophagy in human hepatic carcinoma and glioma cells. In conclusion, this study not only provides a feasible and alternative way exploring new molecular mechanisms of drugs by combing computation DTI prediction, but also reveals an effective strategy to reinforce the antitumor efficacy of Ixabepilone.
- |||||||||| Journal: Down-regulation of PHLPP1 expression ameliorates high glucose-induced autophagy inhibition and apoptosis promotion of podocytes by activating PI3K/AKT/mTOR pathway (Pubmed Central) - Feb 2, 2021
According to the different treatment of podocytes, the cells were divided into NG group (podocytes cultured with normal glucose media), HG group (podocytes cultured with high glucose medium), HG combined with si-PHLPP1 group (podocytes transfected with si-PHLPP1 were cultured in high glucose medium), and HG combined with HCQ group (podocytes treated with hydroxychloroquine and high glucose medium)...The autophagy level of HG combined with HCQ group was significantly inhibited, the apoptosis rate and c-caspase-3 protein expression were significantly raised, and other indicators showed no significant changes. Conclusion PHLPP1 is highly expressed in renal tissue of patients with DN, and the down-regulated expression of PHLPP1 in podocytes can promote the autophagy of podocytes and reduced the apoptosis of podocytes by activating PI3K/AKT/mTOR pathway.
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