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- | sirolimus / Generic mfg.
Preclinical, Journal, IO biomarker: Saikosaponin D Inhibits the Proliferation and Promotes the Apoptosis of Rat Hepatic Stellate Cells by Inducing Autophagosome Formation. (Pubmed Central) - Aug 31, 2021
Autophagy agonist rapamycin had the same effect as SSd and autophagy inhibitor 3-methyladenine could neutralize the effect of SSd in acetaldehyde-activated HSC-T6 cells. SSd could inhibit the proliferation and promote the apoptosis of HSC-T6 cells by inducing autophagosome formation.
- | Preclinical, Journal: Penicillin disrupts mitochondrial function and induces autophagy in colorectal cancer cell lines. (Pubmed Central) - Aug 31, 2021
The cell cycle was arrested at the G phase, the number of early apoptotic cells increased and the protein expression level of cleaved caspase-3 increased, while penicillin-induced apoptosis was blocked by the autophagy inhibitor 3-MA. In conclusion, penicillin disrupted mitochondrial function and energy metabolism in the colorectal cancer cells, which resulted in the induction of autophagic apoptosis and ultimately the inhibition of cancer cell growth and metastasis.
- | Preclinical, Journal: Melatonin Attenuates Dextran Sodium Sulfate Induced Colitis in Obese Mice. (Pubmed Central) - Aug 29, 2021
We also found that melatonin could reduce the ability of inflammatory cells to utilize fatty acids and decrease the growth-promoting effect of lipids by inhibiting autophagy. Taken together, our study indicates that the inhibitory effect of melatonin on autophagy weakens the lipid-mediated prosurvival advantage, which suggests that melatonin-targeted autophagy may provide an opportunity to prevent colitis in obese individuals.
- | Journal: Autophagy is deregulated in cancer-associated fibroblasts from oral cancer and is stimulated during the induction of fibroblast senescence by TGF-β1. (Pubmed Central) - Aug 29, 2021
Lastly, we show that both SAR405- and TGF-β1-treated NHOFs enhance OSCC cell migration but only TGF-β1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-β1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.
- | galunisertib (LY2157299) / Eli Lilly
Journal: Epigallocatechin-3-gallate increases autophagic activity attenuating TGF-β1-induced transformation of human Tenon's fibroblasts. (Pubmed Central) - Aug 29, 2021
But this inhibition effect was rescued by LY2157299, a TGF-βR1 selective inhibitor...Taken together, these findings revealed that autophagic regulation involved in the action of EGCG against TGF-β1-induced transformation of Tenon's fibroblasts. Through increasing intracellular autophagy, EGCG could be a potential anti-fibrotic reagent for preventing subconjunctival fibrosis after glaucoma filtration surgery.
- | Journal: Autophagy blockade limits HER2+ breast cancer tumorigenesis by perturbing HER2 trafficking and promoting release via small extracellular vesicles. (Pubmed Central) - Aug 29, 2021
Our results demonstrate a role for autophagy to promote tumorigenesis in HER2+ breast cancer. This suggests that blocking autophagy could supplement current anti-HER2 agents for treating the disease.
- | Journal: Astaxanthin Inhibits Autophagic Cell Death Induced by Bisphenol A in Human Dermal Fibroblasts. (Pubmed Central) - Aug 28, 2021
Astaxanthin abrogated the ERK-mediated activation of nuclear factor-kappa B (NF-κB), which is responsible for the mRNA expression of LC3-II, Beclin-1, Atg12, and Atg14 during apoptotic cell death induced by BPA. These results indicate that astaxanthin is a pharmacological and nutritional agent that blocks the skin fibroblastic autophagic cell death induced by BPA in human dermal fibroblasts.
- | Journal: Steroidal Saponins Isolated from the Rhizome of Dioscorea tokoro Inhibit Cell Growth and Autophagy in Hepatocellular Carcinoma Cells. (Pubmed Central) - Aug 28, 2021
In contrast, 1-3 did not significantly affect caspase-3 activation and PARP cleavage, suggesting that the antiproliferative activity of 1-3 occurred independently of caspase-3-mediated apoptosis. In summary, our study showed that 1-3, active compounds in the rhizome of D. tokoro, suppressed cell proliferation and autophagy, and might be potential agents for autophagy research and cancer chemoprevention.
- || Review, Journal: Autophagy Modulators in Cancer: Focus on Cancer Treatment. (Pubmed Central) - Aug 28, 2021
Therefore, the precise mechanisms of autophagy modulators and their varied responsiveness to each cancer type should be addressed in detail. This study will describe the precise mechanisms of developing various autophagy modulators, their current therapeutic applications and future perspectives.
- | chloroquine phosphate / Generic mfg.
Journal: Identification of Compound CB-2 as a Novel Late-Stage Autophagy Inhibitor Exhibits Inhibitory Potency against A549 Cells. (Pubmed Central) - Aug 28, 2021
The increased level of LC3B-II induced by CB-2 was neither eliminated when autophagy initiation was suppressed by wortmannin nor further increased when autophagosome degradation was inhibited by chloroquine (CQ)...Scavenging ROS via N-acetylcysteine (NAC) reversed CB-2-induced autophagy inhibition and its inhibitory effect against A549 cells. In conclusion, CB-2 serves as a new late-stage autophagy inhibitor, which has a strong inhibitory potency against A549 cells.
- || chloroquine phosphate / Generic mfg.
Clinical, Journal, Heterogeneity: Effects of the Autophagy-Inhibiting Agent Chloroquine on Acute Myeloid Leukemia Cells; Characterization of Patient Heterogeneity. (Pubmed Central) - Aug 28, 2021
Finally, a minority of patients showed increased extracellular constitutive mediator release in the presence of chloroquine, which was associated with strong antiproliferative effects of chloroquine as well as cytarabine. We conclude that chloroquine has antileukemic activity and should be further explored as a therapeutic drug against AML in combination with other cytotoxic or metabolic drugs; however, due to the patient heterogeneity, chloroquine therapy will probably be effective only for selected patients.
- | Preclinical, Journal: Swainsonine Triggers Paraptosis via ER Stress and MAPK Signaling Pathway in Rat Primary Renal Tubular Epithelial Cells. (Pubmed Central) - Aug 28, 2021
Furthermore, MAPK pathways were activated by SW and inhibitors of ERK and JNK pathways could prevent the formation of cytoplasmic vacuolization. In this study, we confirmed that SW induced cell paraptosis through ER stress and MAPK signaling pathway, thus further laying a theoretical foundation for the study of SW toxicity mechanism.
- | Journal, IO biomarker: Development and validation of a novel survival model for acute myeloid leukemia based on autophagy-related genes. (Pubmed Central) - Aug 28, 2021
Last, we screened drug sensitivity between high- and low-risk subgroups. The risk score model based on 10 autophagy-related genes can serve as an effective prognostic predictor for AML patients and may guide for patient stratification for immunotherapies and drugs.
- | hydroxychloroquine / Generic mfg.
Journal: Furin-instructed aggregated gold nanoparticles for re-educating tumor associated macrophages and overcoming breast cancer chemoresistance. (Pubmed Central) - Aug 28, 2021
Herein, we designed a furin-responsive aggregated nanoplatform loaded with doxorubicin (DOX) and hydroxychloroquine (HCQ) (AuNPs-D&H-R&C) to combine chemotherapy, autophagy inhibition and macrophage polarization...The co-delivery of DOX and HCQ showed much improved chemotherapeutic efficiency to chemoresistant MCF-7/ADR breast tumor, in large part due to macrophage polarization. In conclusion, we developed a stimulus-responsive delivery system and proposed a potential combination strategy to overcome chemoresistance in cancer chemotherapy.
- || Review, Journal: Mitochondrial Modulations, Autophagy Pathways Shifts in Viral Infections: Consequences of COVID-19. (Pubmed Central) - Aug 28, 2021
Modulated autophagy inhibits coronavirus replication; thus, it becomes a promising target for anti-coronaviral therapy. This review gives immense knowledge about the infections, mitochondrial modulations, and therapeutic targets of viruses.
- | Journal: Autophagy Inhibition Plays a Protective Role in Ferroptosis Induced by Alcohol via the p62-Keap1-Nrf2 Pathway. (Pubmed Central) - Aug 28, 2021
Furthermore, inhibition of autophagy increased the expression of p62, which interacted with Keap1 to promote Nrf2 translocation into the nucleus and upregulation its target proteins ferritin heavy (FTH), ferroportin (FPN), and heme oxygenase-1 (HO-1). This study provides a theoretical basis for further elucidation of the relationship between autophagy and ferroptosis and lays a preliminary foundation for further research concerning dietary guidance in the prevention and treatment of diseases related to alcohol-induced ferroptosis.
- | Journal: IKKε knockout alleviates angiotensin II-induced apoptosis and excessive autophagy in vascular smooth muscle cells by regulating the ERK1/2 pathway. (Pubmed Central) - Aug 27, 2021
Collectively, the results of the present study revealed that IKKε played a key role in apoptosis by inducing excessive autophagy, thereby potentially contributing to AAA formation. These findings further revealed the mechanism underlying IKKε function in the formation of AAA.
- | Preclinical, Journal: Inhibition of autophagy promotes human RSV NS1-induced inflammation and apoptosis in vitro. (Pubmed Central) - Aug 27, 2021
Furthermore, the results demonstrated that NS1 activated autophagy partly through the mTOR-p70 S6 kinase signaling pathway. The results suggest that autophagy induced by NS1 transfection through the mTOR pathway can hinder the production of inflammatory cytokines and interferon-α and inhibit cell apoptosis, which may help to explain why autophagy has been shown to be beneficial to viral replication in most studies.
- || cisplatin / Generic mfg.
Review, Journal: Role of autophagy in cholangiocarcinoma: Pathophysiology and implications for therapy. (Pubmed Central) - Aug 27, 2021
In vitro evidence suggests that combination of chemotherapy agents, such as cisplatin, under activation or inhibition of autophagic processes, in two different CCA cell lines, may improve chemosensitivity and reduce cell survival, respectively. A deeper understanding of these pathways, in both cancer and non-cancer cells, could unveil possible therapeutic targets to treat CCA patients.
- | New trial: The Break-Fast study: Effect of a protein-rich breakfast on autophagy in fasting healthy people. (EUDRACT) - Aug 27, 2021
P, N=40, Not yet recruiting, Sponsor: Dr Timothy Sargeant
- | Preclinical, Journal: 3-Acetyldeoxynivalenol induces cell death through endoplasmic reticulum stress in mouse liver. (Pubmed Central) - Aug 27, 2021
In conclusion, using mice as an animal model, we showed that 3-Ac-DON exposure impaired the function of liver, as shown by oxidative damage, cell death, and infiltration of immune cell, in which ER stress played an important role. Restoration of the ER function might be a preventive strategy to reduce the deleterious effect of 3-Ac-DON on the liver of animals.
- | azacitidine / Generic mfg.
Journal: Autophagy Promoted Neural Differentiation of Human Placenta-derived Mesenchymal Stem Cells. (Pubmed Central) - Aug 27, 2021
The blockage and stimulation of autophagy could either hinder or induce the formation of neural-like cells, respectively. Therefore, the refinement of autophagic activity at an appropriate level might improve the efficiency of stem cell differentiation.
- | chloroquine phosphate / Generic mfg.
Preclinical, Journal, IO biomarker: In Vitro Toxicological Assessment of Gadodiamide in Normal Brain SVG P12 Cells. (Pubmed Central) - Aug 27, 2021
Therefore, the refinement of autophagic activity at an appropriate level might improve the efficiency of stem cell differentiation. Normal brain glial SVG P12 cells treated with high concentrations of gadodiamide can undergo autophagy and apoptosis.
- | Ibrance (palbociclib) / Pfizer, Verzenio (abemaciclib) / Eli Lilly
Preclinical, Journal, Combination therapy: Efficacy of a combination therapy targeting CDK4/6 and autophagy in a mouse xenograft model of t(8;21) acute myeloid leukemia. (Pubmed Central) - Aug 26, 2021
These results show that CDK4/6 inhibition induces autophagy, and that co-inhibition of CDK4/6 and autophagy induces apoptosis in t(8;21) AML cells in vivo. The results suggest that inhibiting CDK4/6 and autophagy could be a novel and promising therapeutic strategy in t(8;21) AML.
- | sirolimus / Generic mfg.
Preclinical, Journal: Yi-Zhi-Fang-Dai Formula Exerts a Protective Effect on the Injury of Tight Junction Scaffold Proteins in Vitro and in Vivo by Mediating Autophagy through Regulation of the RAGE/CaMKKβ/AMPK/mTOR Pathway. (Pubmed Central) - Aug 26, 2021
Accordingly, YZFDF increased the expression of the phosphorylated mammalian targets of rapamycin (mTOR), leading to inhibition of autophagy (downregulated LC3 and upregulated P62)...These results suggest that YZFDF restored TJ proteins' injury by suppressing autophagy via RAGE signaling. Furthermore, YZFDF reduced the pathological precipitation of Aβ in the hippocampus, and improved cognitive behavior impairment of the AD model suggested that YZFDF might be a potential therapeutic candidate for treating AD through RAGE/CaMKKβ/AMPK/mTOR-regulated autophagy pathway.
- | Conmana (icotinib) / Betta
Journal: Bisdemethoxycurcumin Enhances the Sensitivity of Non-small Cell Lung Cancer Cells to Icotinib via Dual Induction of Autophagy and Apoptosis. (Pubmed Central) - Aug 25, 2021
Also, 3-MA or CQ can abate the combination treatment-induced apoptosis and DNA damage, suggesting that there is crosstalk between different signaling pathways in the effect produced by the combination treatment. Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.
- | TriptoSar (triptolide) / Pierre Fabre
Preclinical, Journal: Downregulation of miR-200a Protects Mouse Leydig Cells Against Triptolide by Triggering Autophagy. (Pubmed Central) - Aug 25, 2021
These results indicated that downregulation of miR-200a could protect MLTC-1 cells against TP by inducing autophagy. Therefore, miR-200a might serve as a new therapeutic target for the treatment of male hypogonadism.
- | Biomarker, Journal: GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy. (Pubmed Central) - Aug 25, 2021
Furthermore, high expression of critical regulators of glutamine metabolism, GLS1 and MYC, is significantly associated with a decreased progression-free survival in PCa patients treated with radiotherapy. Our findings demonstrate that GLS-driven glutaminolysis is a prognostic biomarker and therapeutic target for PCa radiosensitization.
- | Journal: Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome. (Pubmed Central) - Aug 24, 2021
Importantly, the REV-ERB agonist SR9009 ameliorates abnormal follicular development by promoting mitochondrial biosynthesis and inhibiting autophagy in a mouse PCOS model. This allows us to speculate that SR9009 has potential as a therapeutic agent for the treatment of PCOS.
- | bleomycin / Generic mfg.
Journal: Mechanism of miR-204-5p in exosomes derived from bronchoalveolar lavage fluid on the progression of pulmonary fibrosis via AP1S2. (Pubmed Central) - Aug 24, 2021
PF rat model was established by intratracheal injection of bleomycin...miR-204-5p inhibitor can counteract the effect of PF-Exo in proliferation of lung fibroblasts, while sh-AP1S2 eliminated the effect of miR-204-5p inhibitor. Exosomal miR-204-5p from BALF inhibits autophagy to promote the progression of PF rats by targeting AP1S2.
- | Journal: Silencing c-Jun inhibits autophagy and abrogates radioresistance in nasopharyngeal carcinoma by activating the PI3K/AKT/mTOR pathway. (Pubmed Central) - Aug 24, 2021
c-Jun knockdown increased cell sensitivity to radiation by inhibiting autophagy activation via the PI3K/AKT/mTOR signaling pathway. The present study provides a theoretical basis for a promising treatment for radioresistant NPC by inhibiting c-Jun expression.
- | amiodarone / Generic mfg.
Journal: Regulation of autophagy, glucose uptake, and glycolysis under dengue virus infection. (Pubmed Central) - Aug 22, 2021
Moreover, amiodarone-induced autophagic activity, glucose uptake, HK2 level, and viral titer were reversed by the autophagy inhibitor spautin-1 or silencing of Atg5 gene expression...This is the first report to reveal that DENV2-induced autophagy positively regulates glycolysis and viral replication in vitro and in vivo. Our findings open a new avenue wherein metabolic modulation could be used as a target for the treatment of DENV infection.
- || VTX-11e / Vertex, National Institutes of Health
Clinical, Journal: Blockage of Extracellular Signal-Regulated Kinase Exerts an Antitumor Effect via Regulating Energy Metabolism and Enhances the Efficacy of Autophagy Inhibitors by Regulating Transcription Factor EB Nuclear Translocation in Osteosarcoma. (Pubmed Central) - Aug 21, 2021
In this study, we identified an ERK inhibitor (ERKi; Vx-11e) with potential antitumor activities, which was reflected by the inhibition in the survival and proliferation of Osteosarcoma (OS) cells...Besides, we also found that the ERKi could regulate mitochondrial apoptosis through the ROS/mitochondria pathway and aerobic glycolysis in OS, which also increases the dependence of OS cells on autophagy to clear metabolites to a certain extent. These results may provide a reference for the clinically improved efficacy of ERKis in combination with autophagy inhibitors in the treatment of OS and indicate its potential as a therapeutic agent.
- | Preclinical, Journal: Resveratrol mediates mechanical allodynia through modulating inflammatory response via the TREM2-autophagy axis in SNI rat model. (Pubmed Central) - Aug 21, 2021
These results may provide a reference for the clinically improved efficacy of ERKis in combination with autophagy inhibitors in the treatment of OS and indicate its potential as a therapeutic agent. Taken together, these data reveal that resveratrol relieves neuropathic pain through suppressing microglia-mediated neuroinflammation via regulating the TREM2-autophagy axis in SNI rats.
- | azithromycin / Generic mfg.
Journal: Azithromycin enhances the cytotoxicity of DNA-damaging drugs via lysosomal membrane permeabilization in lung cancer cells. (Pubmed Central) - Aug 21, 2021
Thus, the effects of DOX and AZM were integrated into the marked increase in damaged lysosomes/autolysosomes, leading to prominent lysosomal membrane permeabilization (LMP) for apoptosis induction. Our data suggest that concomitant treatment with DNA-damaging drugs and AZM appears to be a promising strategy for NSCLC treatment via pronounced LMP induction.
- | sirolimus / Generic mfg.
Journal: AQP3-mediated H O uptake inhibits LUAD autophagy by inactivating PTEN. (Pubmed Central) - Aug 21, 2021
Subsequently, we demonstrated that AQP3 was necessary for the facilitated diffusion of exogenous H O in LUAD cells and that the AQP3-dependent transport of H O accelerated cell growth and inhibited rapamycin-induced autophagy...Finally, we suggested that AQP3 depletion retarded subcutaneous tumorigenesis in vivo and simultaneously decreased ROS levels and promoted autophagy. These findings underscore the importance of AQP3-induced oxidative stress in malignant transformation and suggest a therapeutic target for LUAD.
- | Preclinical, Journal: HMGB1 could restrict 1,3-β-glucan induced mice lung inflammation by affecting Beclin1 and Bcl2 interaction and promoting the autophagy of epithelial cells. (Pubmed Central) - Aug 21, 2021
Our finding suggested that silencing HMGB1 could aggravate the 1,3-β-glucan induced lung inflammation by inhibiting the autophagy of epithelial cells. And ubiquitination of Beclin1 contributed to decreasing the interaction of Beclin1 and Bcl2, which might be a key regulatory mechanism of HMGB1 on 1,3-β-glucan induced autophagy.
- | Journal: Progranulin Protects Against Airway Remodeling Through the Modulation of Autophagy via HMGB1 Suppression in House Dust Mite-Induced Chronic Asthma. (Pubmed Central) - Aug 20, 2021
However, enhancement of extracellular HMGB1 levels blunted the inhibition of autophagic flux by PGRN in airway epithelia, thereby resulting in the augmentation of collagen synthesis and fibrosis. Taken together, our data revealed that PGRN protected against asthmatic airway remodeling by negatively regulating autophagy via HMGB1 suppression, which might provide new insights into the therapeutic options for HDM-induced chronic asthma.
- CUDC-305 / Debiopharm, Curis
[VIRTUAL] METPlatform identifies brain metastasis vulnerabilities and predicts patient response to therapy (Channel 2) - Aug 20, 2021 - Abstract #EANO2021EANO_95;
Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is fully compatible with human samples and questions the rationale of excluding patients with brain metastasis from clinical trials. We envision that METPlatform will be established as a clinically relevant strategy to personalize the management of metastatic disease in the brain and elsewhere.
- | Preclinical, Journal: Effects of daphnetin on the autophagy signaling pathway of fibroblast-like synoviocytes in rats with collagen-induced arthritis (CIA) induced by TNF-α. (Pubmed Central) - Aug 20, 2021
DAP also reduced the inflammatory response in CIA-FLS induced by TNF-α by inhibiting the cytokine expression of TNF-α, IL-6, TGF-β, IL-17, and INF-γ and promoting IL-10 expression. Overall, DAP inhibited the proliferation of CIA-FLS by down-regulating the PI3K/AKT/mTOR signaling pathway and inhibited autophagy in order to induces apoptosis, which may be potential therapeutic approach in treatment of RA.
- | sirolimus / Generic mfg.
Preclinical, Journal: Hydroxytyrosol and Oleuropein Inhibit Migration and Invasion via Induction of Autophagy in ER-Positive Breast Cancer Cell Lines (MCF7 and T47D). (Pubmed Central) - Aug 20, 2021
ER-positive BC MCF7 and T47D cells were treated with HT and OL in combination with hepatocyte growth factor (HGF), rapamycin (Rapa, an agonist of autophagy) or 3-methyladenine (3-MA, an inhibitor of autophagy)...Moreover, HT and OL significantly blocked HGF- or 3-MA-induced cell migration and invasion by reversing LC3II/LC3I and Beclin-1 downregulation and p62 upregulation. These findings revealed that HT and OL could suppress migration and invasion by activating autophagy in ER-positive BC cells, which might be a promising therapeutic strategy.
- | Journal: Does mTORC1 inhibit autophagy at dual stages?: A possible role of mTORC1 in late-stage autophagy inhibition in addition to its known early-stage autophagy inhibition. (Pubmed Central) - Aug 20, 2021
In this perspective, we hypothesize that the localization of mTORC1 and lysosome could be interconnected in a way that manifests regulation of autophagy that is already under progression at the time of mTORC1 activation. This provides a new possibility for autophagy regulation whose complete mechanistic insights remain to be determined.
- | Journal: In silico approaches using pharmacophore model combined with molecular docking for discovery of novel ULK1 inhibitors. (Pubmed Central) - Aug 20, 2021
The present study provides an appropriate guideline for discovering novel ULK1 inhibitors. The novel compound may serve as a good starting point for further development and optimizations.
- | Journal: Cell type-specific YAP1-WWTR1/TAZ transcriptional responses after autophagy perturbations are determined by levels of α-catenins (CTNNA1 and CTNNA3). (Pubmed Central) - Aug 20, 2021
These features were integrated into a mathematical numerical model based on a set of differential equations in order to clarify the integrated output on YAP1-WWTR1/TAZ activity at a given time-point of autophagy perturbation in cells with distinct initial levels of α-catenins (CTNNA1 and CTNNA3). Our theoretical and experimental data allow an understanding of cell-type specific and time-dependent responses to autophagy manipulations that may be relevant in many contexts, including different types of cancer.
- | Journal: MicroRNA-146a inhibits autophagy to maintain the intracellular survival of Burkholderia pseudomallei by targeting LIPA. (Pubmed Central) - Aug 20, 2021
Furthermore, overexpression of miR-146a contributed to the defect of autophagic flux caused by B. pseudomallei and was beneficial for the survival of B. pseudomallei in macrophages. Therefore, our findings suggest that miR-146a inhibits autophagy via posttranscriptional suppression of LIPA expression to maintain B. pseudomallei survival in macrophages.
- | Journal, Epigenetic controller: Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes. (Pubmed Central) - Aug 20, 2021
Additionally, we find that MtbPRT induces EZH2 methyltransferase-dependent H3K27me3 hypermethylation and reduces histone acetylation modifications (H3K9ac and H3K27ac) by upregulating histone deacetylase 3 to inhibit autophagy. In summary, this is the first demonstration that Mtb inhibits autophagy by inducing histone hypermethylation in autophagy-related genes to promote intracellular bacterial survival.
- | GNS561 / Genoscience Pharma
Journal, Cancer stem cells: GNS561, a New Autophagy Inhibitor Active against Cancer Stem Cells in Hepatocellular Carcinoma and Hepatic Metastasis from Colorectal Cancer. (Pubmed Central) - Aug 19, 2021
Thus, GNS561 offers great promise for cancer therapy by exterminating both the tumor bulk and the CSC sub-population. Accordingly, a global phase 1b clinical trial in liver cancers was recently completed.
- | metformin / Generic mfg., sevoflurane / Generic mfg.
Preclinical, Journal: Metformin Attenuates Sevoflurane-induced Neurocognitive Impairment Through AMPK-ULK1-dependent Autophagy in Aged Mice. (Pubmed Central) - Aug 19, 2021
These results suggest that metformin attenuates sevoflurane-induced neurocognitive impairment through AMPK-ULK1-dependent autophagy in aged mice. Metformin could become a useful drug to ameliorate cognitive impairment in elderly patients after anaesthesia and surgery.
- | Journal: LncRNA BDNF-AS promotes autophagy and apoptosis in MPTP-induced Parkinson's disease via ablating microRNA-125b-5p. (Pubmed Central) - Aug 19, 2021
Metformin could become a useful drug to ameliorate cognitive impairment in elderly patients after anaesthesia and surgery. Our study demonstrated that knockdown of BDNF-AS could elevate SH-SY5Y cell viability, inhibit autophagy and apoptosis in MPTP-induced PD models through regulating miR-125b-5p, suggesting that BDNF-AS might act as a potential therapeutic target for PD.
- | sirolimus / Generic mfg.
Journal: Autophagy facilitates type I collagen synthesis in periodontal ligament cells. (Pubmed Central) - Aug 19, 2021
E-64d and PSA treatment suppressed and rapamycin treatment accelerated the hard tissue-forming ability of HPDL cells. Our findings suggest that autophagy is a crucial regulatory process that facilitates type I collagen synthesis and partly regulates osteoblastic differentiation of PDL cells.