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  • ||||||||||  Journal, IO biomarker:  Calycosin may alleviate Ang II-induced pro-proliferative effects on glomerular mesangial cells via partially inhibiting autophagy and ERK signaling pathway. (Pubmed Central) -  Aug 18, 2021   
    We found that Ang II increased viability and proliferation, meanwhile inhibited apoptosis of the GMCs; furthermore, 1 and 10 μM calycosin significantly inhibited the growth and promoted the apoptosis of the GMCs treated by Ang II; moreover, calycosin also inhibited ERK signaling in mesangial cells activated by Ang II treatment; Finally, calycosin could inhibit Ang II induced autophagy of GMCs in a dose-dependent manner. In conclusion, calycosin may alleviate Ang II-induced pro-proliferative and anti-apoptotic effects on glomerular mesangial cells at least partially via inhibiting autophagy and ERK signaling pathway, suggesting that calycosin may function as a potential alternative medication for the management of chronic kidney diseases.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal, PARP Biomarker, IO biomarker:  Iron Overload Induces Apoptosis and Cytoprotective Autophagy Regulated by ROS Generation in Mc3t3-E1 Cells. (Pubmed Central) -  Aug 18, 2021   
    What's more, pretreatment with autophagy inhibitor chloroquine (CQ) enhanced iron overload-induced osteoblast apoptosis via the activation of caspases...Inhibition of autophagy increased ROS production, and scavenging of ROS by antioxidant N-Acetyl-L-cysteine (NAC) inhibited caspases activity and rescued iron overload-induced apoptosis. These results suggested that autophagy exerted cytoprotective effect, and scavenging excessive intracellular ROS could be a novel approach for the treatment of iron overload-induced osteoporosis.
  • ||||||||||  Journal:  Host Defense against Klebsiella pneumoniae Pneumonia Is Augmented by Lung-Derived Mesenchymal Stem Cells. (Pubmed Central) -  Aug 18, 2021   
    Adoptive transfer of Sca-1 LMSCs in K. pneumoniae -infected mice improved survival, reduced inflammatory cells in bronchoalveolar lavage fluid, reduced inflammatory cytokine levels and pathological lesions in the lung, and enhanced bacterial clearance in the lung and in extrapulmonary organs. To our knowledge, these results together illustrate for the first time the protective role of LMSCs in bacterial pneumonia.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Hypo-Expression of Tuberin Promotes Adenomyosis via the mTOR1-Autophagy Axis. (Pubmed Central) -  Aug 17, 2021   
    Rapamycin treatment suppressed cell proliferation, migration and EMT in the absence of TSC2...Finally, SAR-405 treatment promoted EMT and migration of overexpressing cells. Collectively, our results suggest that TSC2 controls endometrial epithelial cell migration and EMT by regulating mTOR1-autophagy axis activation and that hypo-expression of TSC2 in the endometrium might promote adenomyosis.
  • ||||||||||  disulfiram / Generic mfg., docetaxel / Generic mfg.
    Journal:  Disulfiram potentiates docetaxel cytotoxicity in breast cancer cells through enhanced ROS and autophagy. (Pubmed Central) -  Aug 14, 2021   
    Furthermore, we also suggest that TFEB can positively act on the autophagy-lysosome pathway and influence the expression of immunocytokines in DCs. This study indicates that DTX + DSF combination therapy can effectively sensitize cancer cells by hyper inducing autophagy through ROS generation and can be developed as a therapeutic strategy for cancer treatment in the future.
  • ||||||||||  Journal:  LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM. (Pubmed Central) -  Aug 14, 2021   
    We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.
  • ||||||||||  Preclinical, Journal, IO biomarker:  Breast milk MSCs upregulated β-cells PDX1, Ngn3, and PCNA expression via remodeling ER stress /inflammatory /Apoptotic signaling pathways in type 1 diabetic rats. (Pubmed Central) -  Aug 13, 2021   
    And, for the first time, our results revealed that intraperitoneally transplanted Br-MSCs homed to the diabetic islet and improved fasting blood glucose, serum insulin level, pancreatic oxidative stress, upregulated pancreatic mRNA expression for: regenerative markers (Pdx1, Ngn3, PCNA), INS, beta-cell receptors (IRS1, IRβ, PPARγ), pancreatic growth factors (IGF-1, VEGFβ1, FGFβ), anti-inflammatory cytokine (IL10) and anti-apoptotic marker (BCL2) too, Br-MSCs downregulated pancreatic mRNA expression for: inflammatory markers (NFKβ, TNFα, IL1β, IL6, IL8, MCP1), apoptotic markers for both intrinsic and extrinsic pathways (FAS, FAS-L, P53, P38, BAX, Caspase3), ER stress markers (ATF6, ATF3, ATF4, BIP, CHOP, JNK, XBP1) and autophagy inhibitor (mTOR). In conclusion, Br-MSCs could be considered as a new insight in beta cell regenerative therapy improving the deteriorated diabetic islet microenvironment via modulating; ER stress, inflammatory, and apoptotic signaling pathways besides, switching on the cellular quality control system (autophagy) thus enhancing beta-cell function.
  • ||||||||||  Journal:  Resveratrol induces AMPK and mTOR signaling inhibition-mediated autophagy and apoptosis in multiple myeloma cells. (Pubmed Central) -  Aug 12, 2021   
    Resveratrol increased the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase and decreased the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream substrates p70S6K and 4EBP1 in a dose-dependent manner, leading to autophagy. Therefore, our results suggest that resveratrol exerts anti-MM effects through apoptosis and autophagy, which can be used as a new therapeutic strategy for MM in clinic.
  • ||||||||||  telmisartan / Generic mfg.
    Journal:  Autoantibody against angiotensin II type I receptor induces pancreatic β-cell apoptosis via enhancing autophagy. (Pubmed Central) -  Aug 12, 2021   
    Meanwhile, it was determined that treatment with autophagy inhibitor 3-methyladenine and angiotensin II type 1 receptor (AT1R) blocker telmisartan could improve insulin secretion and apoptosis in vitro and in vivo. In conclusion, it is deduced that upregulation of autophagy contributed to the AT1-AA-induced β-cell apoptosis and islet dysfunction, and AT1R mediated the signal transduction.
  • ||||||||||  Journal:  Apelin/APJ signaling activates autophagy to promote human lung adenocarcinoma cell migration. (Pubmed Central) -  Aug 12, 2021   
    In conclusion, it is deduced that upregulation of autophagy contributed to the AT1-AA-induced β-cell apoptosis and islet dysfunction, and AT1R mediated the signal transduction. Our studies demonstrate that apelin-induced autophagy promotes lung adenocarcinoma cell migration which suggests a potential therapeutic target for lung adenocarcinoma.
  • ||||||||||  sirolimus / Generic mfg.
    Preclinical, Journal:  The regulatory role of autophagy in rats lung ischemia/reperfusion injury (Pubmed Central) -  Aug 11, 2021   
    Forty SD rats were randomly divided into 5 groups (n=8): ①Sham operated group (sham group):just open rat chest for 3.5 h; ②Ischemia/reperfusion group (I/R group):after open chest, clamp pulmonary hilus for 0.5h then reperfusion for 3 h; ③Solvent group (DMSO group): intraperitoneal injection of DMSO solution for 1h before operation; ④Autophagic inhibitor group (3-MA group); ⑤Autophagic agonist group (Rap group): intraperitoneal injection of autophagic agonist rapamycin before operation; the rest operations of DMSO, 3-MA and Rap groups are the same as that of I/R group...Besides, there was no significant difference among I/R, DMSO and Rap groups (P＞0.05). Autophagy can be activated during ischemia/reperfusion in rats to induce lung injury.
  • ||||||||||  Journal:  Punicalagin attenuates osteoarthritis progression via regulating Foxo1/Prg4/HIF3α axis. (Pubmed Central) -  Aug 11, 2021   
    These findings suggest that donepezil effectively protected the heart against I/R injury through cardiac mitochondrial protection regardless of the time of administration. PUN attenuates LPS-induced chondrocyte injury and osteoarthritis progression by regulating Foxo1/Prg4/HIF3α axis.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Proliferation of Lung Epithelial Cells Is Regulated by the Mechanisms of Autophagy Upon Exposure of Soots. (Pubmed Central) -  Aug 10, 2021   
    It can be said that distinct autophagic mechanisms are operational in cell proliferation of lung epithelial cells due to soots, which may be responsible for different diseases. Understanding the mechanism of these pathways provides some important targets, which can be utilized for the development of future therapeutics.
  • ||||||||||  amiodarone / Generic mfg.
    Journal:  Autophagy alleviates amiodarone-induced hepatotoxicity. (Pubmed Central) -  Aug 8, 2021   
    In conclusion, we demonstrate that amiodarone induces lipid accumulation associated with ER stress and apoptosis in hepatocytes, which is mirrored by increased keratin-18 fragment serum levels in amiodarone-treated patients. Autophagy reduces amiodarone-mediated lipotoxicity and could provide a therapeutic strategy for protection from drug-induced liver injury.
  • ||||||||||  Review, Journal:  Impact of Sodium-Glucose Co-Transporter 2 Inhibitors on Cardiac Protection. (Pubmed Central) -  Aug 8, 2021   
    Recently, dynamic communication between autophagy and the innate immune system with Beclin 1-TLR9-SIRT3 complexes in response to SGLT2 inhibitors that may serve as a potential treatment strategy for heart failure was discovered. In this review, the background molecular pathways leading to the clinical benefits are examined in this new class of anti-diabetic drugs, the SGLT2 inhibitors.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal, PARP Biomarker:  Rice Husk Silica Liquid Protects Pancreatic β Cells from Streptozotocin-Induced Oxidative Damage. (Pubmed Central) -  Aug 7, 2021   
    Interestingly, using autophagy inhibitors such as 3-methyladenine (3-MA) and chloroquine (CQ) both showed an increase in cleaved-PARP protein level, indicating apoptosis induction. Taken together, this study demonstrated that RHSL induced autophagy and alleviated STZ-induced ROS-mediated apoptosis in RIN-m5F cells.
  • ||||||||||  Journal:  Muscovy duck reovirus promotes virus replication by inhibiting autophagy-lysosomal degradation pathway. (Pubmed Central) -  Aug 7, 2021   
    In addition, the experiment detected the maturation of the lysosomal acid hydrolase Cathepsin D in the cells, and found that the expression of the 33 kDa mature form of Cathepsin D was significantly reduced after MDRV infection, indicating that MDRV inhibits the maturation of lysosomes. In general, MDRV infection induces autophagy of DF-1 cells, promotes the fusion of autophagosomes and lysosomes, inhibits autophagolysosome degradation, and promotes virus replication.
  • ||||||||||  Visudyne (verteporfin) / Novartis
    Journal, PD(L)-1 Biomarker, IO biomarker:  Targeting YAP-p62 signaling axis suppresses the EGFR-TKI-resistant lung adenocarcinoma. (Pubmed Central) -  Aug 7, 2021   
    Finally, we suggest that targeting YAP-p62 signaling axis can be useful to suppress the EGFR-TKI-resistant lung cancer. Therefore, drug repurposing of verteporfin for lung cancer treatment may be valuable to consider because it can inhibit critical targets: p62, YAP, and PD-L1 at the same time.
  • ||||||||||  Journal:  SOD1-interacting proteins: Roles of aggregation cores and protein degradation systems. (Pubmed Central) -  Aug 6, 2021   
    These SOD1-interacting proteins were involved in multiple cellular functions such as protein quality control, cytoskeletal organization, and pathways involved in growth factor signaling and their downstream cascades. The complex interactions between pathways could cause further dysregulation, ultimately leading to fatal cellular dysfunction in ALS.
  • ||||||||||  Journal:  Myofibril Assembly and the Roles of the Ubiquitin Proteasome System. (Pubmed Central) -  Aug 6, 2021   
    In the presence of p97 and proteasomal inhibitors the dynamics of each of these two myosin proteins decreased in the nascent myofibril stage, but were unaffected in the mature myofibril stage. The increased stability of myofibrils occurring in the transition from nascent to mature myofibril assembly indicates the importance of dynamics and selective destruction in the muscle myosin II proteins for the remodeling of nascent to mature myofibrils.
  • ||||||||||  carfilzomib / Generic mfg.
    Journal:  Pten Deficiency Leads To Proteasome Addiction, A Novel Vulnerability In Glioblastoma. (Pubmed Central) -  Aug 6, 2021   
    Our findings highlight the feasibility of combining autophagy inhibition and ASP in the treatment of ENKTCL. Proteasome inhibition is a potential synthetic lethal therapeutic strategy for GBM with proteasome addiction due to a high protein synthesis rate and autophagy deficiency.
  • ||||||||||  monalizumab (IPH2201) / AstraZeneca, Innate, ezurpimtrostat (GNS561) / Genoscience Pharma, Genfit, avdoralimab (IPH5401) / Innate
    Enrollment closed, Trial completion date, Metastases:  IMMUNONCOVID: Prospective Study in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 Infection (clinicaltrials.gov) -  Aug 5, 2021   
    P2,  N=219, Active, not recruiting, 
    These results suggest the potential therapeutic value of the dual targeting of the proteasome and HDCA6 for head and neck cancers through the induction of necroptosis-like cell death along with ROS generation. Recruiting --> Active, not recruiting | Trial completion date: Aug 2021 --> Dec 2021