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  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Ononin alleviates HO-induced cardiomyocyte apoptosis and improves cardiac function by activating the AMPK/mTOR/autophagy pathway. (Pubmed Central) -  Sep 30, 2021   
    However, these anti-apoptotic effects mediated by ON were lost after autophagy inhibition by chloroquine or AMPK inhibition by Compound C. Finally, the protective effects of ON on cardiomyocytes in vitro could also be observed in vivo...Using echocardiography and Masson's staining, ON was shown to increase the ejection fraction and decrease cardiac fibrosis in rats with myocardial infarction. These results suggest that ON exerts cardioprotective effects by improving autophagy via the AMPK/mTOR signaling pathway.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Autophagy inhibition blunts PDGFRA adipose progenitors' cell-autonomous fibrogenic response to high-fat diet. (Pubmed Central) -  Sep 30, 2021   
    We found that autophagy inhibition promotes global cell-autonomous remodeling of the paracrine TGF-BMP family landscape, whereas ECM gene modulation was independent of the autophagic regulation of GTF2IRD1. The progenitor-specific mouse model of ATG7 inhibition confirms the requirement of autophagy for white/beige adipocyte turnover, and combined to in vitro experiments, reveal progenitor autophagy dependence for AT fibrogenic response to HFD, through the paracrine remodeling of TGF-BMP factors balance.Abbreviations: CQ: chloroquine; ECM: extracellular matrix; EpiAT: epididymal adipose tissue; GTF2IRD1: general transcription factor II I repeat domain-containing 1; HFD: high-fat diet; KO: knockout; OvAT: ovarian adipose tissue; PDGFR: platelet derived growth factor receptor; ScAT: subcutaneous adipose tissue; TGF-BMP: transforming growth factor-bone morphogenic protein.
  • ||||||||||  Preclinical, Journal:  Microglial autophagy defect causes parkinson disease-like symptoms by accelerating inflammasome activation in mice. (Pubmed Central) -  Sep 30, 2021   
    Interestingly, we found that serum MIF levels in PD patients were significantly elevated. Taken together, our results reveal an important role of autophagy in microglial activation-driven PD-like symptoms, thus providing potential targets for the clinical treatment of PD.Abbreviations: ATG: autophagy related; cAMP: cyclic adenosine monophosphate; cKO: conditional knockout; NOS2/INOS: nitric oxide synthase 2, inducible; IL1B: interleukin 1 beta; ITGAM/CD-11b: integrin alpha M/cluster of differentiation molecule 11B; MAP1LC3: microtubule-associated protein 1 light chain 3; MIF: macrophage migration inhibitory factor (glycosylation-inhibiting factor); NLRP3: NLR family pyrin domain containing 3; PBS: phosphate-buffered saline; PD: parkinson disease; PDE10A: phosphodiesterase 10A; SN: substantial nigra; TH: tyrosine hydroxylase; TNF: tumor necrosis factor; WT: wild type.
  • ||||||||||  chloroquine phosphate / Generic mfg., hydroxychloroquine / Generic mfg.
    Journal:  Chloroquine induces apoptosis in PanNEN via endoplasmic reticulum stress. (Pubmed Central) -  Sep 30, 2021   
    In the HCQ group, histological analyses revealed that proliferative activity was unchanged, but apoptosis was accelerated, accompanied by CHOP expression. These results suggest that autophagy inhibition by CQ/HCQ could be used for the treatment of PanNEN, including the well-differentiated type.
  • ||||||||||  Review, Journal:  The Controversial Role of Autophagy in Ewing Sarcoma Pathogenesis-Current Treatment Options. (Pubmed Central) -  Sep 30, 2021   
    Monitoring and targeting autophagy in every ES patient could eliminate the need for targeting multiple pathways in order to achieve the maximum beneficial effect. Future studies are required to focus on which ES patients are affected by autophagy modulators in order to provide novel and more efficient therapeutic protocols for patients with ES based on the current autophagy status of the tumors.
  • ||||||||||  temozolomide / Generic mfg.
    Journal:  Gymnema sylvestre Extract Restores the Autophagic Pathway in Human Glioblastoma Cells U87Mg. (Pubmed Central) -  Sep 29, 2021   
    Novel natural molecules and phyto-extracts have been proposed as adjuvants to sensitise the response to Temozolomide (TMZ)...Furthermore, as main key regulators of type II programmed cell death, p53, p21 and CDK4 were also investigated and were inhibited by GS treatment. In conclusion, GS extract could be considered as an autophagy inducer in glioblastoma cells U87Mg.
  • ||||||||||  Review, Journal:  Crosstalk between Autophagy and Inflammatory Processes in Cancer. (Pubmed Central) -  Sep 29, 2021   
    On that basis, we focus on autophagy inhibitors and activators regulating inflammatory process in cancer as useful candidates for enhancing anticancer effects. This review summarizes how the autophagic process regulates these key inflammatory processes and vice versa in various cancers.
  • ||||||||||  Preclinical, Journal:  Role of Luteolin-Induced Apoptosis and Autophagy in Human Glioblastoma Cell Lines. (Pubmed Central) -  Sep 29, 2021   
    Results showed that luteolin induces apoptosis and autophagy and that the luteolin-induced autophagy promotes cell survival. Therefore, an appropriate combination therapy involving luteolin and an autophagy inhibitor is expected to improve the prognosis of GBM treatment.
  • ||||||||||  Journal:  Endothelial autophagy deficiency induces IL6 - dependent endothelial mesenchymal transition and organ fibrosis. (Pubmed Central) -  Sep 29, 2021   
    The plasma level of IL6 was higher in Atg5 Endo compared to that of control mice, and fibrosis was accelerated in Atg5 Endo treated with a HFD; neutralization of IL6 by a specific antibody inhibited EndMT and fibrosis in HFD-fed Atg5 Endo associated with the amelioration of metabolic defects. These results revealed the essential role of autophagy in endothelial cell integrity and revealed that the disruption of endothelial autophagy could lead to significant pathological IL6-dependent EndMT and organ fibrosis.Abbreviations: 3-MA: 3-methyladenine; ATG5: autophagy related 5; EndMT: endothelial-to-mesenchymal transition; HES: hematoxylin and eosin stain; HFD: high-fat diet; HMVECs: human microvascular endothelial cells; IFNG: interferon gamma; IL6: interleukin 6; MTS: Masson's trichrome staining; NFD: normal-fat diet; siRNA: small interfering RNA; SMAD3: SMAD family member 3; TGFB: transforming growth factor β; TNF: tumor necrosis factor; VEGFA: vascular endothelial growth factor A.
  • ||||||||||  tamoxifen / Generic mfg.
    Journal:  Rubicon in pancreatic beta cells plays a limited role in maintaining glucose homeostasis following increased insulin resistance. (Pubmed Central) -  Sep 29, 2021   
    Next, we generated pancreatic beta-cell-specific Rubicon knockout (βKO) mice, by administering tamoxifen to Rubicon:MIP-Cre-ERT mice, which showed normal glucose tolerance and insulin secretion under a normal chow diet, despite successful gene recombination...Finally, severe insulin resistance was induced with insulin receptor antagonist treatment, which resulted in comparable glucose homeostasis measurements between Rubicon βKO and control mice. In summary, these results suggest that in pancreatic beta cells, Rubicon plays a limited role in the maintenance of systemic glucose homeostasis.
  • ||||||||||  Journal:  A novel Diels-Alder adduct of mulberry leaves exerts anticancer effect through autophagy-mediated cell death. (Pubmed Central) -  Sep 29, 2021   
    GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as "autophagy-mediated cell death." Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.
  • ||||||||||  doxorubicin hydrochloride / Generic mfg.
    Journal:  The effects and mechanisms of aloe-emodin on reversing adriamycin-induced resistance of MCF-7/ADR cells. (Pubmed Central) -  Sep 29, 2021   
    In addition, the combination of AE and ADR arrested G2/M cell cycle and induced apoptosis through DNA damage, ROS generation, caspase-3 activation. Our study indicated that AE could be a potential reversal agent to resensitize ADR resistant in tumor chemotherapy and inhibiting autophagy might be an effective strategy to further enhance the reversal activity of AE.
  • ||||||||||  Journal:  Apigenin enhances viability of random skin flaps by activating autophagy. (Pubmed Central) -  Sep 29, 2021   
    Interestingly, 3-methyladenine reversed the effects of apigenin on flap survival, angiogenesis, apoptosis, and oxidative stress through inhibition of autophagy. The findings of this study show that apigenin promotes angiogenesis, inhibits cell apoptosis, and lowers oxidative stress by mediating autophagy, thus the improving survival rate of random skin flaps.
  • ||||||||||  Jakafi oral (ruxolitinib) / Novartis, Incyte
    Journal:  JAK/STAT pathway promotes the progression of diabetic kidney disease via autophagy in podocytes. (Pubmed Central) -  Sep 29, 2021   
    Studies using ruxolitinib inhibitors have showed that suppression of the JAK/STAT pathway in podocytes subjected to high glucose could increase autophagic flux and autophagy-related protein expression. Taken together, the present study demonstrates that high glucose inhibits autophagy by activating the JAK/STAT pathway in mice and podocytes, thereby preventing the efficient removal of damaged proteins and organelles from the body to prevent apoptosis, and ultimately aggravating the progression of podocyte injury and DKD.
  • ||||||||||  Review, Journal:  Anaplasmataceae: Dichotomous Autophagic Interplay for Infection. (Pubmed Central) -  Sep 29, 2021   
    In this review, the recent findings regarding how these master manipulators engage and inhibit autophagy for infection are explored. Future investigation to understand mechanisms used by Anaplasmataceae to exploit autophagy may advance novel antimicrobial therapies and provide new insights into how intracellular microbes exploit autophagy to survive.
  • ||||||||||  CBT-1 (tetrandrine) / CBA Pharma
    Journal:  Autophagy inhibition enhances anti-pituitary adenoma effect of tetrandrine. (Pubmed Central) -  Sep 29, 2021   
    Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.
  • ||||||||||  Journal:  Activation of Autophagy Relieves Linoleic Acid-Induced Inflammation in Large Yellow Croaker (Larimichthys crocea). (Pubmed Central) -  Sep 29, 2021   
    Furthermore, autophagy could alleviate LA-induced inflammatory cytokine gene expression in vivo and in vitro, while inhibition of autophagy obtained the opposite results. In conclusion, our study shows that autophagy could regulate inflammation and alleviate LA-induced inflammation in the liver of large yellow croaker in vivo and in vitro for the first time, which may offer considerable benefits to the aquaculture industry and human health.
  • ||||||||||  Preclinical, Journal:  Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of Salmonella Typhimurium by Enhancing Autophagy in Murine Macrophages. (Pubmed Central) -  Sep 28, 2021   
    Intracellular microtubule-associated protein 1A/1B-light chain 3 (LC3) levels were increased in poly(I:C)-treated cells; however, they were decreased in cells pretreated with 3-methyladenine (3-MA)-a commonly used inhibitor of autophagy. These results suggest that poly(I:C) induces autophagy and enhances ROS production via MEK1/2-mediated signaling to suppress intracellular bacterial growth in S. Typhimurium-infected murine macrophages, and that a TLR3 agonist could be developed as an immune enhancer to protect against S. Typhimurium infection.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Platelet-Rich Plasma Induces Autophagy and Promotes Regeneration in Human Dental Pulp Cells. (Pubmed Central) -  Sep 28, 2021   
    The effect of PRP on cellular migration, proliferation, and osteogenic differentiation was further investigated in the milieu of autophagy activator, rapamycin, and inhibitor, 3-methyladenine...Autophagy inhibition suppressed PRP-induced hDPCs migration, proliferation, and osteogenic differentiation, whereas autophagy activator substantially augmented PRP-stimulated migration, proliferation, and differentiation. Taken together, these findings suggested that PRP could effectively promote regenerative potentials associated with autophagy.
  • ||||||||||  cucurbitacin I (JSI-124) / H. Lee Moffitt Cancer Center and Research Institute, University of South Florida
    [VIRTUAL] STAT3 Inhibitor JSI-124 Induces Autophagic Cell Death in RN5 Murine Mesothelioma Cells () -  Sep 26, 2021 - Abstract #IMIG2021IMIG_53;    
    RN5 cells were pretreated with 3-methyladenine (2.5 mM) or chloroquine (50 µM) for 1h, and then coincubation with JSI-124 for another 24 h. Levels of protein expression were analyzed by western blot using antibodies against caspase 3, PARP, MAP1LC3B-II, p-mTOR/p-p70S6K and p-JAK2/p-STAT3. STAT3 inhibitor JSI-124 induces protective autophagy in RN5 murine mesothelioma cells through mTOR/p70S6K signaling pathway, suggesting that JSI-124 may be a potential therapeutic strategy for MPM.