- |||||||||| tyrphostin (AG 490) / EMD Serono, Yissum Research Development Company
Journal: Inhibition of JAK2 by AG490 promotes TNF-α-induced apoptosis by inhibiting autophagy in MC3T3-E1 cells. (Pubmed Central) - May 21, 2021 Western blot analysis showed that the STAT3, Akt, and Erk signaling pathways are involved in AG490 treatment. This study demonstrated for the first time that JAK2 inhibition by AG490 may play a crucial role in TNF-α-induced apoptosis by inhibiting autophagy and inhibiting the STAT3, Akt, and Erk signaling pathways.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Downregulation of Ascl2 promotes cell apoptosis by enhancing autophagy in colorectal cancer cells. (Pubmed Central) - May 21, 2021 Furthermore, we treated CRC cells with autophagy inhibitors 3-MA (3-Methyladenine) and CQ (Chloroquine)...Finally, we confirmed that the downregulation of Ascl2 in CRC cells could alleviate the pathological process in vivo by xenograft experiment. Our findings indicated that si-Ascl2 (small/short interfering) exerted a tumor suppression function in CRC by inducing autophagic cell death, and suggest that Ascl2 targeted therapy represents a novel strategy for CRC treatment.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: WDR45 Mutation Impairs the Autophagic Degradation of Transferrin Receptor and Promotes Ferroptosis. (Pubmed Central) - May 21, 2021 TfRC was accumulated after the inhibition of autophagy by treatment with autophagic inhibitor chloroquine or knockdown of ATG2A...Increased TfRC and simultaneously decreased FTH consequently resulted in an elevated level of ferrous iron (Fe) which further promoted cell ferroptosis, demonstrated by the increased lipid peroxidation and reactive oxygen species (ROS) and the decreased glutathione peroxidase 4 (GPX4) and cell viability. Taken together, these findings provide a piece of important evidence that WDR45 deficiency impairs autophagic degradation of TfRC, therefore leading to iron accumulation, and the elevated iron promotes ferroptosis which may contribute to the progression of BPAN.
- |||||||||| Journal: Identification of autophagy inhibiting factors of Mycobacterium tuberculosis by high throughput loss of function screening. (Pubmed Central) - May 20, 2021
Differential expression of these PE/PPE proteins was observed in response to various stress conditions, suggesting that they may confer advantages to M. tuberculosis by modulating its interactions with host cells under various conditions. Our findings demonstrated that multiple M. tuberculosis PE/PPE proteins are involved in inhibiting autophagy during infection of host phagocytes and may provide strategic targets in developing therapeutics or vaccines against tuberculosis.
- |||||||||| imatinib / Generic mfg.
Journal: Expansion of senescent megakaryocyte-lineage cells maintains CML cell leukemogenesis. (Pubmed Central) - May 20, 2021 Furthermore, BCR-ABL-expressing MgkL cells displayed enhanced autophagic activity, and autophagy inhibition reduced bone marrow MgkL cell number and prolonged the survival of CML mice, which had transiently received the tyrosine kinase inhibitor, imatinib, earlier. Thus, BCR-ABL induced the expansion of senescent leukemic MgkL cells, which supported CML leukemogenesis by providing TGF-β1.
- |||||||||| sirolimus / Generic mfg.
Journal: Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis. (Pubmed Central) - May 20, 2021 The inhibitory effects of fucoidan on NLRP3 inflammasome were enhanced by autophagy activator rapamycin (Rapa) and alleviated by autophagy inhibitor 3-methyladenine (3-MA)...Knockdown of p62 and ATG5 by small interfering RNA significantly reduced the inhibitory effects of fucoidan treatment on NLRP3 inflammasome. The data suggest that fucoidan can inhibit NLRP3 inflammasome activation by enhancing p62/SQSTM1-dependent selective autophagy to alleviate atherosclerosis.
- |||||||||| Journal: Autophagy is Involved in Neuroprotective Effect of Alpha7 Nicotinic Acetylcholine Receptor on Ischemic Stroke. (Pubmed Central) - May 20, 2021
Moreover, we found that PNU282987 treatment could activate the AMPK-mTOR-p70S6K signaling pathway in the in vitro study, while the effect was attenuated by compound C, an AMPK inhibitor. Our results demonstrated that the beneficial effect on neuronal survival via activation of α7nAChR was associated with enhanced autophagy, and the AMPK-mTOR-p70S6K signaling pathway was involved in α7nAChR activation-mediated neuroprotection.
- |||||||||| sirolimus / Generic mfg.
Journal: Circular RNA ciRS-7 inhibits autophagy of ESCC cells by functioning as miR-1299 sponge to target EGFR signaling. (Pubmed Central) - May 15, 2021 Of interest, in the present work, we observed that ciRS-7 could inhibit starvation or rapamycin-induced autophagy of ESCC cells and miR-1299 promotes starvation or rapamycin-induced autophagy of ESCC cells...Consistent with our past findings, ciRS-7 could also sponge miR-1299 in ESCC cells. Taken together, this study has shed light on that circular RNA ciRS-7 inhibits autophagy of ESCC cells by functioning as miR-1299 sponge to target EGFR signaling.
- |||||||||| Journal: Targeting the miR-122/PKM2 autophagy axis relieves arsenic stress. (Pubmed Central) - May 15, 2021
We also found that miR-122 knockdown positively regulated the PI3K/Akt/mTOR pathway, and this phenomenon was reversed by cotransfecting cells with si-PKM2. Taken together, our findings show that the miR-122/PKM2 autophagy axis protects hepatocytes from arsenite stress via the PI3K/Akt/mTOR pathway; thus, miR-122 may be a potential candidate in the treatment of arseniasis.
- |||||||||| chloroquine phosphate / Generic mfg., ibandronate sodium hydrate / Generic mfg.
Journal: Activation of autophagy during farnesyl pyrophosphate synthase inhibition is mediated through PI3K/AKT/mTOR signaling. (Pubmed Central) - May 15, 2021 The inhibition of glutamine isozymes reduces autophagy and apoptosis in astrocytes, and inhibits pancreatic cancer cell proliferation and metastasis, while reducing their invasiveness. These findings provide insights into the role of autophagy in the cardioprotective effects of IBAN and the molecular mechanisms underlying autophagy induction by IBAN.
- |||||||||| sirolimus / Generic mfg.
Journal: Autophagy is Required for Remodeling in Postnatal Developing Ribbon Synapses of Cochlear Inner Hair Cells. (Pubmed Central) - May 15, 2021 Treatment of mice at P7 with rapamycin or 3-methyladenine (activator and inhibitor of autophagy, respectively) for 7 days led to the significant elevations of hearing threshold across frequencies from P15 to P30...Thus, our study demonstrated that autophagy was required for remodeling of cochlear ribbon synapses and provided a new insight into autophagy-related hearing disorder during auditory development. Furthermore, we implicated a novel therapeutic target for sensorineural hearing loss.
- |||||||||| Journal: CdSe/ZnS quantum dots induced spermatogenesis dysfunction via autophagy activation. (Pubmed Central) - May 15, 2021
Consequently, injection of autophagy inhibitor (3-MA) restore DSB repair in spermatocytes, resulting in prevention of spermatocyte apoptosis and recovery of spermatogenesis. Our studies strongly indicate that autophagy is key for eliciting the spermatogenesis dysfunction after nanoparticle exposure, and autophagy inhibition can be used as a potential clinical remedy for alleviating the male reproductive toxicity of nanoparticles.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Autophagy-inhibiting polymer as an effective nonviral cancer gene therapy vector with inherent apoptosis-sensitizing ability. (Pubmed Central) - May 15, 2021 The copolymerization of methacryloyl chloroquine (MACQ) with 2-(dimethylamino)ethyl methacrylate (DMAEMA) not only improves transfection efficacy through hydrophobic modification, but also endows the copolymer with autophagy-blocking capability, which further sensitizes cancer cells to TRAIL induced apoptosis...In contrast, TRAIL gene delivered by the autophagy-blocking-deficient control copolymer without the chlorine atom presents weaker antitumor efficacy, although expressing a similar amount of therapeutic TRAIL protein. Thus, this study demonstrates a conceptually new approach in which the therapeutic outcome of the delivered gene can be inherently strengthened by the delivery vehicle with intrinsic pharmacological activity.
- |||||||||| Journal: Enhanced hyaluronan signaling and autophagy dysfunction by VPS35 D620N. (Pubmed Central) - May 15, 2021
We report that knockdown of HMMR or CD44 results in upregulated autophagy in cells expressing wild-type VPS35. However, only HMMR knockdown resulted in rescue of autophagy dysfunction by VPS35 D620N indicating a potential pathogenic role for this receptor and hyaluronan signaling in Parkinson's disease.
- |||||||||| Journal: mTORC1-dependent TFEB nucleus translocation and pro-survival autophagy induced by zeolitic imidazolate framework-8. (Pubmed Central) - May 15, 2021
Most importantly, doxorubicin-encapsulated ZIF-8 (DOX@ZIF-8) also elicited strong pro-survival autophagy, and the co-delivery of an autophagic inhibitor (3-MA) dramatically enhanced the cytotoxicity of DOX@ZIF-8 in HeLa cells. Our results revealed the unique ability of ZIF-8, both in a free and drug-loaded form, to induce pro-survival autophagy in certain cancer cells, a finding with important implications for potential clinical studies that utilize ZIF-8 as a drug carrier.
- |||||||||| Journal: Heterozygous disruption of beclin 1 mitigates arsenite-induced neurobehavioral deficits via reshaping gut microbiota-brain axis. (Pubmed Central) - May 15, 2021
Our results illustrated for the first time that heterozygous disruption of beclin 1, which played a central role in autophagy, alleviated the perturbation of gut microbiome phenotypes induced by arsenite, and ultimately leading to the improvement of neurobehavioral deficits through gut-brain communication. These findings provide a new clue that regulation of autophagy is a potential approach for probing the functional impacts of arsenite on the gut microbiome, and it also may be severed as a way for protection strategies against arsenite neurotoxicity.
- |||||||||| chloroquine phosphate / Generic mfg., hydroquinone / Generic mfg.
Journal: Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells. (Pubmed Central) - May 15, 2021 Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 - expressing cells in the presence of chloroquine...Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment...The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.
- |||||||||| docetaxel / Generic mfg.
Journal: Hierarchical assembly of dual-responsive biomineralized polydopamine-calcium phosphate nanocomposites for enhancing chemo-photothermal therapy by autophagy inhibition. (Pubmed Central) - May 15, 2021 The first step in the self-assembly process involves the incorporation of hydrophobic chemotherapeutic docetaxel (DTX) into the CaP nanoparticles...Third, the autophagy inhibitor chloroquine (CQ) was absorbed onto the surface of PDA via non-covalent interactions, forming PCNPs/DC...Interestingly, complementary autophagy inhibition could therefore sensitize the effects of chemo-photothermal therapy both in vitro and in vivo with negligible toxicity. Therefore, these hierarchically assembled biomineralized nanocomposites would be used as a prevailing strategy to sensitize chemo-photothermal therapy by complementary autophagy inhibition.
- |||||||||| sirolimus / Generic mfg.
Journal: Aldosterone enhances high phosphate-induced vascular calcification through inhibition of AMPK-mediated autophagy. (Pubmed Central) - May 15, 2021 Moreover, inhibiting adenosine monophosphate-activated protein kinase (AMPK) by Compound C attenuated Aldo/MR-enhanced VC. These results suggested that Aldo facilitates high Pi-induced VSMC osteogenic phenotypic switch and calcification through MR-mediated signalling pathways that involve AMPK-dependent autophagy, which provided new insights into Aldo excess-associated VC in various settings.
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