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  • ||||||||||  Autophagy-related risk loci in SLE and their role in neutrophils (Poster View 1) -  Apr 21, 2022 - Abstract #EULAR2022EULAR_1747;    
    Functional characterization of SNPs on the PRDM1-ATG5 and ATG16L2-P2RY2 loci, and the functional characterization of ATG16L2 in myeloid and neutrophil cell lines, provide new insights into the mechanisms that regulate autophagy in health and disease. Ongoing studies will focus on in vitro validation of predicted functional SNPs and will introduce ATG16L2 rs11235604 risk variant in PLB-985 cells to assess its importance in autophagy.
  • ||||||||||  Journal:  Enhancing anti-tumor immunity by autophagy inhibition. (Pubmed Central) -  Apr 20, 2022   
    Ongoing studies will focus on in vitro validation of predicted functional SNPs and will introduce ATG16L2 rs11235604 risk variant in PLB-985 cells to assess its importance in autophagy. No abstract available
  • ||||||||||  gemcitabine / Generic mfg.
    Journal:  Lucidone inhibits autophagy and MDR1 via HMGB1/RAGE/PI3K/Akt signaling pathway in pancreatic cancer cells. (Pubmed Central) -  Apr 20, 2022   
    Gemcitabine (GEM) drug resistance remains a difficult challenge in pancreatic ductal adenocarcinoma (PDAC) treatment...In addition, remarkable cell proliferation was observed after treatment with lucidone combined with GEM, particularly in MIA Paca-2 cells, indicating that lucidone treatment enhanced chemosensitivity. Collectively, this study provided the underlying mechanism by which lucidone treatment inhibited HMGB1/RAGE-initiated PI3K/Akt/MDR1 signaling and consequently enhanced chemosensitivity in PDAC.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Neospora caninum infection activated autophagy of caprine endometrial epithelial cells via mTOR signaling. (Pubmed Central) -  Apr 20, 2022   
    Further studies showed that N. caninum infection induced autophagy through inhibition of mTOR phosphorylation. To the best of our current knowledge, this is the first study to reveal the role of autophagy during N. caninum infection in caprine EECs, and the findings provided significant information for uncovering mechanisms of abortion and pathogenicity caused by N. caninum infection.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Knockout of GGPPS1 restrains rab37-mediated autophagy in response to ventilator-induced lung injury. (Pubmed Central) -  Apr 20, 2022   
    The benefits of GGPPS1 knockout for VILI can be partially eliminated through treatment with rapamycin...Simultaneously, Rab37 overexpression significantly enhances autophagy in cells that are treated with cyclin stretch, including GGPPS1 knockout cells. Collectively, our results indicate that GGPPS1 knockout results in reduced expression of Rab37 proteins, further restraining autophagy and VILI.
  • ||||||||||  Journal:  An autophagy-related protein Becn2 regulates cocaine reward behaviors in the dopaminergic system. (Pubmed Central) -  Apr 19, 2022   
    Inactivating Becn2 by upstream autophagy inhibitors stabilizes striatal presynaptic D2R, reduces dopamine release and signaling, and prevents cocaine reward in normal mice. Thus, the autophagy protein Becn2 is essential for cocaine psychomotor stimulation and reward through regulating dopamine neurotransmission, and targeting Becn2 by autophagy inhibitors is a potential strategy to prevent cocaine-induced behaviors.
  • ||||||||||  sirolimus / Generic mfg., dantrolene / Generic mfg.
    Journal:  Aeromonas hydrophila inhibits autophagy triggering cytosolic translocation of mtDNA which activates the pro-apoptotic caspase-1/IL-1β-nitric oxide axis in headkidney macrophages. (Pubmed Central) -  Apr 19, 2022   
    Elevated mitochondrial ROS (mtROS) was recorded which declined significantly by ameliorating ER-stress and in the presence of ER-Ca release modulators (2-APB and dantrolene) and mitochondrial-Ca uptake inhibitor, Ru360, together suggesting the role of ER-mitochondrial Ca dynamics in mtROS generation...Our results with autophagy-inducer rapamycin demonstrated that impaired autophagy favored the cytosolic accumulation of mitochondrial DNA (mtDNA) and the process depended on mtROS levels...Our study suggests a novel role of ER-mitochondria cross-talk in regulating A. hydrophila pathogenesis. Based on our observations, we conclude that A. hydrophila induces ER-stress and inhibits mitophagy resulting in mitochondrial dysfunction which leads to mtROS production and translocation of mtDNA into cytosol triggering the activation of caspase-1/IL-1β-mediated NO production, culminating in HKM apoptosis.
  • ||||||||||  bortezomib / Generic mfg.
    Journal:  NEDD4L binds the proteasome and promotes autophagy and bortezomib sensitivity in multiple myeloma. (Pubmed Central) -  Apr 19, 2022   
    Suppression of NEDD4L expression reduced bortezomib (Bor) sensitivity in vitro and in vivo, mainly through autophagy inhibition mediated by low NEDD4L expression, which was rescued by an autophagy activator. Clinically, elevated expression of NEDD4L is associated with a considerably increased probability of responding to Bor, a prolonged response duration, and improved overall prognosis, supporting both the use of NEDD4L as a biomarker to identify patients most likely to benefit from Bor and the regulation of NEDD4L as a new approach in myeloma therapy.
  • ||||||||||  chloroquine phosphate / Generic mfg., metformin / Generic mfg.
    Review, Journal:  The Two-Faced Role of Autophagy in Endometrial Cancer. (Pubmed Central) -  Apr 19, 2022   
    Furthermore, the biguanide diabetes drug metformin, treatment with which enhances autophagy via AMPK-mediated mTOR inactivation, has been reported to reduce the risk of EC...Consistent with this, treatment with chloroquine, an autophagy inhibitor, is reported to attenuate EC cell proliferation...In conclusion, autophagy plays a dual role in the prevention and treatment of EC. Therefore, targeting autophagy to prevent and treat EC requires diametrically opposed strategies.
  • ||||||||||  pevonedistat (MLN4924) / Takeda
    Review, Journal:  Autophagy Agents in Clinical Trials for Cancer Therapy: A Brief Review. (Pubmed Central) -  Apr 15, 2022   
    Pevonedistat has emerged as a novel inhibitor through the neddylation pathway and is an autophagy activator. This paper summarizes and presents current clinical trials for hydroxychloroquine (HCQ), chloroquine (CQ), and Pevonedistat for the clinician.
  • ||||||||||  Journal, IO biomarker:  Residue of thiram in food, suppresses immune system stress signals and disturbs sphingolipid metabolism in chickens. (Pubmed Central) -  Apr 15, 2022   
    The results on different metabolome investigation showed that the sphingolipid metabolism in the thymus of chicks exposed to thiram was disrupted resulting in up-regulation of metabolites related to cell membrane components such as SM, galactosylceramide and lactosylceramide. The results of our experimental research suggest that thiram can interfere with the sphingolipid metabolism in thymus and angiogenesis, inhibit the proliferation of vascular endothelial cells to induce potential toxic effects in chicken.
  • ||||||||||  Journal:  Decorin Protects Retinal Pigment Epithelium Cells from Oxidative Stress and Apoptosis via AMPK-mTOR-Regulated Autophagy. (Pubmed Central) -  Apr 15, 2022   
    Furthermore, DCN activated the AMPK/mTOR pathway to promote autophagy while genetic inhibition of autophagy-related gene 5 (ATG5) hindered autophagic process and diminished the protective role of DCN against oxidative stress in ARPE-19 cells. Collectively, these results suggest that DCN could protect RPE cells from HO-induced oxidative stress and apoptosis via autophagy promotion, thus providing the therapeutic potential for AMD prevention and treatment.
  • ||||||||||  Journal:  A LysR Transcriptional Regulator Manipulates Macrophage Autophagy Flux During Brucella Infection. (Pubmed Central) -  Apr 15, 2022   
    Compared with the wild-type strain, Δ0858 mutant can stimulate the conversion of LC3-I to LC3-II and markedly inhibited the autophagy flux at early stage leading to obvious autophagosome accumulation. This study explored the function of BSS2_II0858 gene and may provide new insights for understanding the mechanisms involved in the survival of Brucella in macrophages.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Preclinical, Journal:  Calycosin ameliorates atherosclerosis by enhancing autophagy via regulating the interaction between KLF2 and MLKL in apoE mice. (Pubmed Central) -  Apr 14, 2022   
    The role of ASPP2-mTORC1-ERS axis was verified in hepatocyte injury, which suggests the possibility that ASPP2 is an important regulatory molecule for the survival and death of hepatocyte. This study demonstrated the atheroprotective effect of calycosin was through upregulating KLF2-MLKL-mediated autophagy, which not only proposed novel mechanistic insights into the atherogenesis but also identified calycosin as a potential drug candidate for atherosclerosis treatment.
  • ||||||||||  ulinastatin injection / Generic mfg.
    Preclinical, Journal:  Ulinastatin improves renal microcirculation by protecting endothelial cells and inhibiting autophagy in a septic rat model. (Pubmed Central) -  Apr 14, 2022   
    This study demonstrated the atheroprotective effect of calycosin was through upregulating KLF2-MLKL-mediated autophagy, which not only proposed novel mechanistic insights into the atherogenesis but also identified calycosin as a potential drug candidate for atherosclerosis treatment. Ulinastatin effectively protects the adhesion junction and helps ameliorate the perfusion of kidney capillaries during sepsis by the inhibition of autophagy and the expression of inflammatory factors.