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  • ||||||||||  hydroxychloroquine / Generic mfg., albumin-bound paclitaxel / Generic mfg., gemcitabine / Generic mfg.
    Trial completion, Trial completion date, Trial primary completion date, Combination therapy:  A Phase I/II/Pharmacodynamic Study of Hydroxychloroquine in Combination With Gemcitabine/Abraxane to Inhibit Autophagy in Pancreatic Cancer (clinicaltrials.gov) -  Apr 1, 2022   
    P1/2,  N=119, Completed, 
    AOPPs may induce trophoblast cell senescence by inhibiting the autophagy process in a p53/mTOR/p70S6K-dependent pathway. Active, not recruiting --> Completed | Trial completion date: Dec 2021 --> Mar 2022 | Trial primary completion date: Dec 2021 --> Mar 2022
  • ||||||||||  hydroxychloroquine / Generic mfg.
    Journal:  Radiosensitizing pancreatic cancer via effective autophagy inhibition. (Pubmed Central) -  Mar 31, 2022   
    Finally, in vivo sub-cutaneous tumor models demonstrate that combination of RT and EAD1 is the most successful at controlling tumor growth. The models also confirmed a similar toxicity profile between EAD1 and HCQ.
  • ||||||||||  Journal:  microRNA-17-5p downregulation inhibits autophagy and myocardial remodelling after myocardial infarction by targeting STAT3. (Pubmed Central) -  Mar 31, 2022   
    Then, after inhibiting STAT3 expression using STAT3 inhibitor S31-201, the fibrosis, scarring, and cardiomyocyte apoptosis were deteriorated, along with the rise of LC3-II/LC3-I and Beclin-1 expression, the reduction of p62 expression and the reversion of MI attenuation. In conclusion, inhibition of miR-17-5p can inhibit myocardial autophagy through targeting STAT3 and then inhibit myocardial remodelling, thereby protecting the myocardium after MI.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Increased Drp1 promotes autophagy and ESCC progression by mtDNA stress mediated cGAS-STING pathway. (Pubmed Central) -  Mar 31, 2022   
    In conclusion, inhibition of miR-17-5p can inhibit myocardial autophagy through targeting STAT3 and then inhibit myocardial remodelling, thereby protecting the myocardium after MI. Our finding reveals that Drp1 overexpression induces mitochondrial dysfunction and cytosolic mtDNA stress, which subsequently activates the cGAS-STING pathway, triggers autophagy and promotes ESCC progression.
  • ||||||||||  Preclinical, Review, Journal:  Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response. (Pubmed Central) -  Mar 30, 2022   
    With respect to the context-dependent role of autophagy in prostate cancer, genetic tools such as siRNA and CRISPR-Cas9 can be utilized for targeting autophagic genes. Finally, these findings can be translated into preclinical and clinical studies to improve survival and prognosis of prostate cancer patients.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Preclinical, Journal:  THE EFFECTS OF AUTOPHAGY INHIBITION BY CHLOROQUINE ON HEPATIC STELLATE CELL ACTIVATION IN CCl -INDUCED ACUTE LIVER INJURY MOUSE MODEL. (Pubmed Central) -  Mar 29, 2022   
    Our results indicated that GATA3 overexpression improved the therapeutic effects of rBMSCs transplantation against ischemic stroke induced injury by regulating autophagy through CREG. The autophagy attenuation exerted by CQ together with the reduction of the expression of the proliferation marker in HSCs can lessen the acute liver damage potentially opening the way to novel therapeutic approaches for hepatic fibrosis.
  • ||||||||||  Journal:  FSH inhibits autophagy and lysosomal biogenesis to regulate protein degradation in cultured goat Sertoli cells. (Pubmed Central) -  Mar 29, 2022   
    Moreover, we found that the FSH-mediated inhibition of autophagy extends the biological half-lives of androgen-binding protein (ABP), glial-derived neurotrophic factor (GDNF), and stem cell factor (SCF) and promotes the secretion of these proteins. Collectively, these observations indicate that FSH inhibits autophagy by reducing lysosomal biogenesis, which is associated with the suppression of TFEB nuclear translocation via activation of the PI3K/Akt/mTOR pathway, thereby extending the biological half-lives and enhancing the expression of ABP, GDNF, and SCF in dairy goat Sertoli cells.
  • ||||||||||  Preclinical, Journal:  α-synuclein suppresses microglial autophagy and promotes neurodegeneration in a mouse model of Parkinson's disease. (Pubmed Central) -  Mar 29, 2022   
    Functionally, the in vivo evidence showed that lysozyme 2 Cre (Lyz2 )-mediated depletion of autophagy-related gene 5 (Atg5) in microglia aggravated the neuroinflammation and dopaminergic neuron losses in the SN and exacerbated the locomotor deficit in α-Syn-overexpressing mice. Taken together, the results suggest that extracellular α-Syn, via Tlr4-dependent p38 and Akt-mTOR signaling cascades, disrupts microglial autophagy activity which synergistically contributes to neuroinflammation and PD development.
  • ||||||||||  temozolomide / Generic mfg.
    Journal, PARP Biomarker, IO biomarker:  CN-3 increases TMZ sensitivity and induces ROS-dependent apoptosis and autophagy in TMZ-resistance glioblastoma. (Pubmed Central) -  Mar 29, 2022   
    Many glioma patients develop resistance to temozolomide (TMZ) treatment, resulting in reduced efficacy and survival rates...In addition, CN-3 promoted SHG44R and U87R cells sensitive to TMZ by reducing the expression of P-gp, MGMT, and nuclear factor kappa B p65, and it had a synergistic cytotoxic effect with TMZ. Moreover, CN-3 disrupted the natural cycle arrest and inhibited the migration of SHG44R and U87R cells by promoting cyclin E1 and D1, and by decreasing P21, P27, N-cadherin, β-catenin, transforming growth factor beta 1, and Smad2.
  • ||||||||||  Preclinical, Journal:  Neuroprotective role of DL-3-n-butylphthalide via the Nrf2/SIRT3 pathway in a mouse model of vascular dementia. (Pubmed Central) -  Mar 29, 2022   
    The results indicated that NBP treatment ameliorated learning and memory deficits, attenuated pathological damage in the CA1 regions, and reduced autophagy and apoptosis via the Nrf2/SIRT3 pathway after repeated cerebral I/R. Therefore, NBP treatment can improve the learning and cognitive memory of VD mice, possibly through the inhibition of autophagy and apoptosis mediated by the Nrf2/SIRT3 signaling pathway.
  • ||||||||||  Journal:  Protective effect of HS on LPS‑induced AKI by promoting autophagy. (Pubmed Central) -  Mar 29, 2022   
    The results revealed that 3‑MA eliminated the protective effect of NaHS in HK‑2 cells and AKI mice. Overall, NaHS can protect from LPS‑induced AKI by promoting autophagy and inhibiting apoptosis and the release of inflammatory factors.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Programmed Catalytic Therapy-Mediated ROS Generation and T-Cell Infiltration in Lung Metastasis by a Dual Metal-Organic Framework (MOF) Nanoagent. (Pubmed Central) -  Mar 27, 2022   
    With the assistance of Chloroquine (CQ), the inhibition of autophagy through lysosomal deacidification breaks off the self-defense mechanism and further improves the cytotoxicity...The effective catalytic dual MOF integrated dysfunctional autophagy at the metastasis elicits the ~3-fold recruitment of T lymphocytes. Such synergy of T cell recruitment and ROS generation transported by dual MOF during the metastases successfully suppresses more than 90% of tumor foci in the lung.
  • ||||||||||  cisplatin / Generic mfg.
    Journal:  MAP4K4 mediates the SOX6-induced autophagy and reduces the chemosensitivity of cervical cancer. (Pubmed Central) -  Mar 26, 2022   
    Moreover, cisplatin itself could promote the expression of endogenous SOX6 and subsequently the MAP4K4-mediated autophagy in cervical cancer cells, which might in turn reduce the sensitivity of these cells to cisplatin treatment. These findings uncovered the underlying mechanism and potential significance of SOX6-induced autophagy, and shed new light on the usage of MAP4K4 inhibitor or autophagy-specific inhibitor for sensitizing cervical cancer cells to the platinum-based chemotherapy.
  • ||||||||||  Journal:  Occurrence of Total and Proteinase K-Resistant Alpha-Synuclein in Glioblastoma Cells Depends on mTOR Activity. (Pubmed Central) -  Mar 26, 2022   
    A high amount of α-syn was documented in GBM cells via real-time PCR (RT-PCR), Western blotting, immunohistochemistry, immuno-fluorescence, and ultrastructural stoichiometry, compared with the amount of β- and γ-synucleins and compared with the amount of α-syn counted within astrocytes. The present study indicates that (i) α-syn is overexpressed in GBM cells, (ii) α-syn expression includes a proteinase-K resistant isoform, (iii) α-syn is dispersed from autophagy-like vacuoles to the cytosol, (iv) α-syn overexpression and cytosol dispersion are mitigated by rapamycin, and (v) the α-syn-related GBM-like phenotype is mitigated by silencing the SNCA gene.
  • ||||||||||  Journal:  Rapamycin relieves the cataract caused by ablation of Gja8b through stimulating autophagy in zebrafish. (Pubmed Central) -  Mar 25, 2022   
    These data suggest an unrecognized cataractogenesis mechanism caused by ablation of Gja8b and a potential treatment for cataracts by stimulating autophagy in the lens. Abbreviations: 3-MA: 3-methyladenine; ATG: autophagy related; AV: autophagic vacuoles; Dpf: days post fertilization; GJA1: gap junction protein alpha 1; GJA3: gap junction protein alpha 3; GJA8: gap junction protein alpha 8; Hpf: hours post fertilization; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PtdIns3K: class III phosphatidylinositol 3-kinase; WT: wild type.
  • ||||||||||  Journal:  Ferulic Acid Exerts Neuroprotective Effects via Autophagy Induction in C. elegans and Cellular Models of Parkinson's Disease. (Pubmed Central) -  Mar 25, 2022   
    Moreover, FA was able to induce autophagy in stable GFP-RFP-LC3 U87 cells and PC-12 cells, while bafilomycin A1 (Baf, an autophagy inhibitor) partly eliminated the protective effects of FA against 6-OHDA- and HO-induced cell death and ROS production in PC-12 cells, further confirming that FA exerts an anti-PD effect via autophagy induction in vitro. Collectively, our study provides novel insights for FA as a potent autophagy enhancer to effectively prevent neurodegenerative diseases such as PD in the future.
  • ||||||||||  Journal:  Diosmetin Protects against Cardiac Hypertrophy via p62/Keap1/Nrf2 Signaling Pathway. (Pubmed Central) -  Mar 25, 2022   
    Similarly, the Nrf2 inhibitor ML385 obviously abolished the above effects by diosmetin treatment. In conclusion, our results suggest that diosmetin protects cardiac hypertrophy under pressure overload through the p62/Keap1/Nrf2 signaling pathway, suggesting the potential of diosmetin as a novel therapy for pathological cardiac hypertrophy.
  • ||||||||||  Journal:  Evaluation of BPA effects on autophagy in Neuro-2a cells. (Pubmed Central) -  Mar 25, 2022   
    qRT-PCR results showed that the relative expression level of autophagy-related p62 mRNA increased significantly and that the relative expression level of Beclin1 mRNA decreased significantly with increasing BPA concentration. The above results indicated that BPA treatment exerted dose-dependent toxic effects on Neuro-2a cells, and BPA inhibited the autophagy level of Neuro-2a cells, thereby providing a new perspective in studying the toxic effect of BPA on Neuro-2a cells.
  • ||||||||||  Preclinical, Journal:  Calcitonin gene-related peptide exerts inhibitory effects on autophagy in the heart of mice. (Pubmed Central) -  Mar 24, 2022   
    Similar effects were observed in cardiomyocytes, in which CGRP also inhibited autophagic flux and stimulated Akt and FoxO phosphorylation. These findings suggest that CGRP in vivo acutely suppresses autophagy in the heart of fed and fasted mice, most likely through the activation of PKA/mTORC1 signaling but independent of Akt.
  • ||||||||||  dorsomorphin (Compound C) / EMD Serono
    Journal:  PPARβ/δ accelerates bone regeneration in diabetic mellitus by enhancing AMPK/mTOR pathway-mediated autophagy. (Pubmed Central) -  Mar 24, 2022   
    These findings suggest that CGRP in vivo acutely suppresses autophagy in the heart of fed and fasted mice, most likely through the activation of PKA/mTORC1 signaling but independent of Akt. In conclusion, our study demonstrates the potential role of PPARβ/δ as a molecular target for the treatment of impaired bone quality and delayed bone healing in diabetic patients for the first time.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  MyD88 deficiency ameliorates weight loss caused by intestinal oxidative injury in an autophagy-dependent mechanism. (Pubmed Central) -  Mar 24, 2022   
    In conclusion, our study demonstrates the potential role of PPARβ/δ as a molecular target for the treatment of impaired bone quality and delayed bone healing in diabetic patients for the first time. MyD88 modulates intestinal oxidative stress in an autophagy-dependent mechanism, which suggests that reducing MyD88 level may constitute a putative therapeutic target for intestinal oxidative injury-induced weight loss.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Autophagic Schwann cells promote perineural invasion mediated by the NGF/ATG7 paracrine pathway in pancreatic cancer. (Pubmed Central) -  Mar 24, 2022   
    Autophagic SCs exert a "nerve-repair like effect", induce a high level of autophagy of cancer cells, provide a "beacon" for the invasion of cancer cells to nerve fibers, and induce directional growth of cancer cells. Targeting NGF and autophagy for PNI treatment can block nerve infiltration and is expected to provide new directions and an experimental basis for the research and treatment of nerve infiltration in pancreatic cancer.