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  • ||||||||||  Review, Journal:  The Potential Role of Connexins in the Pathogenesis of Atherosclerosis. (Pubmed Central) -  Feb 12, 2023   
    A better understanding of the complexity of atherosclerosis pathophysiology linked with Cx could result in developing novel therapeutic strategies. This review aims to present the role of Cx in the pathogenesis of atherosclerosis and discusses whether they can become novel therapeutic targets.
  • ||||||||||  icaritin (SNG-162) / Shenogen Pharma
    Journal:  Icaritin Derivative IC2 Induces Cytoprotective Autophagy of Breast Cancer Cells via SCD1 Inhibition. (Pubmed Central) -  Feb 12, 2023   
    Overall, our study was the first to demonstrate that IC2 induced cytoprotective autophagy by SCD1 inhibition in breast cancer cells and that the autophagy inhibitor markedly enhanced the anticancer activity of IC2. Therefore, IC2 was a potential candidate compound in combination therapy for breast cancer.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Inhibition of Autophagy Increases Cell Death in HeLa Cells through Usnic Acid Isolated from Lichens. (Pubmed Central) -  Feb 11, 2023   
    Interestingly, co-treatment with chloroquine (CQ), an autophagy inhibitor, increased the cytotoxic potential of the UC2A extract...A decrease in zeta potential and a 40% increase in caspase 3/7 activity were also noted after CQ treatment of UA-treated cells. Thus, cytotoxicity of UA can be increased by inhibiting autophagy.
  • ||||||||||  Journal:  AVE 0991 Suppresses Astrocyte-Mediated Neuroinflammation of Alzheimer's Disease by Enhancing Autophagy. (Pubmed Central) -  Feb 10, 2023   
    Furthermore, the inhibitory effect of AVE 0991 on the expression of inflammatory factors was reversed by 3-MA, an autophagy inhibitor. These findings suggest that regulation of autophagy is critical for inhibiting astrocyte neuroinflammatory responses and demonstrate a potential neuroprotective mechanism by which AVE 0991 could suppress neuroinflammatory responses by enhancing autophagy.
  • ||||||||||  sirolimus / Generic mfg.
    Journal, PARP Biomarker:  Enhancing autophagy leads to increased cell death in radiation-treated cervical cancer cells. (Pubmed Central) -  Feb 9, 2023   
    HeLa and CaSki cells were irradiated with ?-rays (2?Gy/min) after treatment with an autophagy inducer (rapamycin) and inhibitor (3-MA)...Apoptosis occurred later than autophagy in radiation treatment, and inhibition of autophagy derived a decrease in apoptosis.What the implications are of these findings for clinical practice and/or further research? Our results suggest that radiation-induced autophagy may be regulated by modulators, and autophagy augmentation yields an increase in cervical cancer cell death under radiation.
  • ||||||||||  sirolimus / Generic mfg.
    Preclinical, Journal:  Benzo[a]pyrene induces epithelial tight junction disruption and apoptosis via inhibiting the initiation of autophagy in intestinal porcine epithelial cells. (Pubmed Central) -  Feb 8, 2023   
    To investigate the role of autophagy on B[a]P-induced epithelial tight junction disruption and apoptosis, cells were cotreated with B[a]P and rapamycin, and rapamycin dramatically improved intestinal tight junction and reduced apoptosis, indicating a protective effect of autophagy for the cells in response to B[a]P treatment...Interestingly, B[a]P-induced apoptosis and dysfunction of the intestinal tight junction were exacerbated by 4-phenylbutyric acid, and the 4-phenylbutyric acid didn't ameliorate the inhibitory effect of B[a]P on microtubule-associated protein 1 light chain 3 (LC3-II) and lysosomal-associated membrane protein 2 (LAMP2) in IPEC-1?cells. These novel findings provided herein indicated that B[a]P induces intestinal epithelial tight junction disruption and apoptotic cell death via inhibiting autophagy in IPEC-1?cells.
  • ||||||||||  Promacta (eltrombopag) / Novartis
    Journal:  A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB. (Pubmed Central) -  Feb 7, 2023   
    These novel findings provided herein indicated that B[a]P induces intestinal epithelial tight junction disruption and apoptotic cell death via inhibiting autophagy in IPEC-1?cells. Here, we show that an United States Food and Drug Administration (FDA)-approved drug Eltrombopag (EO) binds to the basic helix-loop-helix-leucine zipper domain of TFEB, specifically the bottom surface of helix-loop-helix
  • ||||||||||  Journal:  Targeting HIV-1 reservoirs in T cell subsets. (Pubmed Central) -  Feb 7, 2023   
    Co-culture studies showed that T cell subsets latently infected by HIV-1, but not uninfected bystander cells, were susceptible to cell death induced by SECH treatments. Our study suggests that the SECH strategy is effective for specific targeting of latent HIV-1 reservoirs in different T cell subsets.
  • ||||||||||  Preclinical, Journal:  Spautin-1 Protects Against Mild TBI-Induced Anxiety-Like Behavior in Mice via Immunologically Silent Apoptosis. (Pubmed Central) -  Feb 7, 2023   
    Moreover, compared to mice that only underwent TBI, spautin-1 downregulated autophagic vacuoles, abnormal organelles, the expression of Beclin 1, USP13, phospho-TBK1, and phospho-IRF3 and upregulated the levels of cleaved caspase-3, -7 and -9, but failed to increase TUNEL-positive cells in the LHA at 24 h. Spautin-1 alleviated anxiety-like behavior in mice exposed to mild TBI; this protective mechanism may be associated with decreased PNNs loss around GABAergic neurons via immunologically silent apoptosis induced by the caspase cascade.
  • ||||||||||  Journal:  Immortalized Alzheimer's Disease Astrocytes: Characterization of Their Proteolytic Systems. (Pubmed Central) -  Feb 3, 2023   
    Treatment with 4-phenylbutyric acid, a neuroprotective small chemical chaperone, partially restored proteasome and autophagy-mediated proteolysis in 3Tg-iAstro. Our data shed light on the impaired proteostasis in 3Tg-iAstro with proteasome inhibition and autophagic compensatory activation, providing additional validation of this AD in vitro model, and propose a new mechanism of action of 4-phenylbutyric acid in neurodegenerative disorders.
  • ||||||||||  Journal:  ANP promotes HTR-8/SVneo cell invasion by upregulating protein kinase N 3 via autophagy inhibition. (Pubmed Central) -  Feb 2, 2023   
    The increased expression of PKN3 and enhanced cell invasion ability in HTR-8/SVneo cells induced by ANP could be abolished by autophagy activation or transfection with PKN3 shRNA or NFYA shRNA or NPR-A shRNA via regulating the invasion-related genes and the epithelial mesenchymal transition molecules. Our results demonstrated that ANP could enhance trophoblast invasion by upregulating PKN3 via NFYA promotion through autophagy inhibition in an AMPK/mTORC1 signaling-dependent manner.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  β-hydroxybutyrate enhances bovine neutrophil adhesion by inhibiting autophagy. (Pubmed Central) -  Jan 31, 2023   
    To confirm the regulatory role of autophagy in BHB promoting neutrophil adhesion, we used an autophagy activator rapamycin (RAPA)...Furthermore, BHB treatment increased the mRNA abundance and the release of pro-inflammatory factors IL-1B, IL-6, and TNF of bovine neutrophils, and these effects were attenuated by RAPA. Overall, the present study revealed that BHB promotes the adhesion of bovine neutrophils by inhibiting autophagy.
  • ||||||||||  sevoflurane / Generic mfg.
    Preclinical, Journal:  Endoplasmic Reticulum Stress-Activated Neuronal and Microglial Autophagy Contributes to Postoperative Cognitive Dysfunction in Neonatal rats. (Pubmed Central) -  Jan 31, 2023   
    Seven-day old neonatal rats (P7) had right common carotid artery exposure under anesthesia with 3% sevoflurane for 2 h...The ER stress activator tunicamycin and inhibitor tauroursodeoxycholic acid increased the markers for autophagy in control rats and decreased the autophagy markers in rats with surgery, respectively. Our results suggest that surgery in neonatal rats induces ER stress that then activates neuronal and microglial autophagy, which contributes to learning and memory impairment later in life.
  • ||||||||||  Journal, Stroma:  Mesenchymal stromal cells ameliorate diabetes-induced muscle atrophy through exosomes by enhancing AMPK/ULK1-mediated autophagy. (Pubmed Central) -  Jan 29, 2023   
    CuMy-12 can be considered a natural candidate with anticancer activity for autophagy-based regulation, but mechanistic and clinical studies are required to validate its potential. Our results suggest that human umbilical cord mesenchymal stromal cells mitigate diabetes- and obesity-induced muscle atrophy via enhancing AMPK/ULK1-mediated autophagy through exosomes, with implications of applying hucMSCs or hucMSC-derived exosomes to treat muscle atrophy.
  • ||||||||||  Journal:  Blockage of autophagosome-lysosome fusion through SNAP29 O-GlcNAcylation promotes apoptosis via ROS production. (Pubmed Central) -  Jan 28, 2023   
    In conclusion, these findings identify a new pathway in autophagy connecting O-GlcNAcylated SNAP29 to autophagic flux blockage and autophagosome accumulation, that, in turn, drives ROS production and apoptotic cell death. Consequently, modulation of SNAP29 activity may represent a new opportunity for therapeutic intervention in cancer and other autophagy-associated diseases.
  • ||||||||||  gefitinib / Generic mfg.
    Journal:  Epidermal growth factor regulates autophagy activity and endocytosis of yak cumulus cells in a concentration-dependent manner. (Pubmed Central) -  Jan 27, 2023   
    Yak cumulus cells were treated with different concentrations of EGF and appropriate concentrations of EGFR inhibitor gefitinib (10 μM)...Noteworthy, EGF can promote endocytosis by regulating the expression of Cav1 and Cav2, but the EGFR-mediated signaling pathway is not the main way to regulate the expression of these proteins. These results provide a reference for further exploring the effects of growth factors on livestock germ cells and the regulatory role of autophagy-endocytosis crosstalk mechanism in follicle development and oocyte maturation, to improve the fecundity of yaks.
  • ||||||||||  Journal:  The COPII subunit MoSec24B is involved in development, pathogenicity and autophagy in the rice blast fungus. (Pubmed Central) -  Jan 27, 2023   
    Deletion of MoSec24B caused reduced lipidation of MoAtg8, accelerated degradation of exogenously introduced GFP-MoAtg8, and increased lipidation of MoAtg8 upon treatment with a late inhibitor of autophagy (BafA1), suggesting that MoSec24B regulates the fusion of late autophagosomes with vacuoles. Together, these results suggest that MoSec24B exerts a significant role in fungal development, the pathogenesis of filamentous fungi and autophagy.
  • ||||||||||  Journal:  PM induces autophagy-dependent ferroptosis by endoplasmic reticulum stress in SH-SY5Y cells. (Pubmed Central) -  Jan 27, 2023   
    We also found that inhibition of both endoplasmic reticulum stress and autophagy reversed the PM -induced increase in the expression level of cytophagy NCOA4. Our results suggested that PM -induced ferroptosis in SH-SY5Y cells was autophagy-dependent ferroptosis due to endoplasmic reticulum stress, which might be associated with the elevation of iron content caused by NCOA4-mediated ferritin autophagy.
  • ||||||||||  Mekinist (trametinib) / Novartis
    Journal:  Inhibition of autophagy and MEK promotes ferroptosis in Lkb1-deficient Kras-driven lung tumors. (Pubmed Central) -  Jan 27, 2023   
    Taken together, we demonstrate that autophagy upregulation in KL tumors causes resistance to Trametinib by inhibiting ferroptosis. Therefore, a combination of autophagy and MEK inhibition could be a novel therapeutic strategy to specifically treat NSCLC bearing co-mutations of LKB1 and KRAS.
  • ||||||||||  5-fluorouracil / Generic mfg., cisplatin / Generic mfg., docetaxel / Generic mfg.
    Role of autophagy and its modulation in Head and neck cancer () -  Jan 25, 2023 - Abstract #ECHNOICHNO2023ECHNO_ICHNO_126;    
    Moreover autophagic marker p62 demonstrated to have a possible prognostic role in patients according to recurrence rate. Conclusion Autophagy may be considered a possible targetable mechanism in head and neck cancer
  • ||||||||||  Journal, IO biomarker:  Leucine mediates cognitive dysfunction in early life stress-induced mental disorders by activating autophagy. (Pubmed Central) -  Jan 24, 2023   
    Ultimately, in vitro experiments suggested that leucine deficiency could activate neuronal autophagy including enhanced LC3II/LC3I and mRFP-GFP-LC3, which was consistent with the in vivo results, and the cell apoptosis rate and lactate dehydrogenase (LDH) cytotoxicity were also increased with leucine deficiency, while the above effects could be partly reversed by autophagy inhibitor treatment. MS model caused adult male rats to be susceptible to cognitive dysfunction, which may regulate autophagy in hippocampal neurons through leucine metabolism in CSF.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Involvement of JNK signaling in Aspergillus fumigatus-induced inflammatory factors release in bronchial epithelial cells. (Pubmed Central) -  Jan 24, 2023   
    In addition, an inhibitor of autophagy, bafilomycin A1 was able to significantly down-regulate the release of inflammatory factors in BEAS-2B cells upon A. fumigatus conidia, while rapamycin could reverse the effect of JNK inhibitor on IL-27 and TNF-α release. Taken together, these data demonstrated that JNK signal might play an important role in inflammatory factor release regulated by autophagy in bronchial epithelial cells against A. fumigatus infection.
  • ||||||||||  Journal:  Cinchonine-induced cell death in pancreatic cancer cells by downregulating RRP15. (Pubmed Central) -  Jan 23, 2023   
    Cinchonine treatment inhibits the expression of RRP15 and autophagy, and caused apoptosis by leading to the activation of Nrf2 axis in pancreatic cancer cells. Taken together, the above results indicate that cinchonine treatment inhibited autophagy and induced apoptosis through activating Nrf2 axis by downregulating RRP15 in pancreatic cancer cells.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Chloroquine Enhances Death in Lung Adenocarcinoma A549 Cells Exposed to Cold Atmospheric Plasma Jet. (Pubmed Central) -  Jan 22, 2023   
    We concluded that CAP weakly activated pro-survival autophagy in irradiated cells, and CQ promoted CAP-dependent cell death due to the destabilization of autophagosomes formation and mitochondria homeostasis. To summarize, the combination of CAP treatment with CQ could be useful for the development of cold plasma-based antitumor approaches for clinical application.
  • ||||||||||  LY294002 / Eli Lilly
    Preclinical, Journal:  GPR30 Alleviates Pressure Overload-Induced Myocardial Hypertrophy in Ovariectomized Mice by Regulating Autophagy. (Pubmed Central) -  Jan 22, 2023   
    In summary, our results demonstrate that G1 can attenuate cardiac hypertrophy and fibrosis and improve the cardiac function of mice in the OVX + TAC group through AKT/mTOR mediated inhibition of autophagy. Thus, this study demonstrates a potential option for the drug treatment of pressure overload-induced cardiac hypertrophy in postmenopausal women.
  • ||||||||||  Preclinical, Journal:  The Effect of Mesenchymal Stem Cells on Dry Eye in Sjogren Syndrome Mouse Model. (Pubmed Central) -  Jan 22, 2023   
    Notably, expression of autophagy markers ATG5 and LC3B-II, as well as HIF-1α and mTOR which play roles in the pathways of autophagy modulation, were shown to be attenuated in the lacrimal glands of hMSCs-treated mice compared to the PBS-treated control mice. Treatment with hMSCs by lacrimal gland or subconjunctival injection demonstrated the alleviation of DE through the repression of autophagy markers, suggesting the therapeutic potentials of hMSCs in a SS mouse model.
  • ||||||||||  deoxyglucose / Generic mfg.
    Journal:  Glycolysis Inhibition of Autophagy Drives Malignancy in Ovarian Cancer: Exacerbation by IL-6 and Attenuation by Resveratrol. (Pubmed Central) -  Jan 22, 2023   
    Of clinical relevance, bioinformatic analysis of The Cancer Genome Atlas dataset revealed that ovarian cancer patients bearing mutated TP53 with low expression of glycolytic markers and IL-6 receptor, together with markers of active autophagy, display a longer overall survival and are more responsive to platinum therapy. Taken together, our findings demonstrate that RV can counteract IL-6-promoted ovarian cancer progression by rescuing glycolysis-mediated inhibition of autophagy and support the view that targeting Warburg metabolism can be an effective strategy to limit the risk for cancer metastasis.