B4GalT1 Regulates Apoptosis and Autophagy of Glioblastoma In Vitro and In Vivo.

payth.elady61 shared this article with you from Inoreader B4GalT1 Regulates Apoptosis and Autophagy of Glioblastoma In Vitro and In Vivo. Via pubmed: autophagy B4GalT1 Regulates Apoptosis and Autophagy of Glioblastoma In Vitro and In Vivo. Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820980104 Authors: Wang P, Li X, Xie Y Abstract Our study was designed to investigate the role of B4GalT1 in glioblastoma, in vitro and in vivo, to detect whether B4GalT1 knockdown could regulate the development of glioblastoma, and further observe the relationship between B4GalT1 knockdown and the apoptosis and autophagy of glioblastoma. To begin, we looked at TCGA and GEPIA systems to predict the potential function of B4GalT1. Western blot and RT-PCR were used to analyze the expression, or mRNA level, of B4GalT1 at different tissue or cell lines. Next, the occurrence and development of glioblastoma, in vitro and in vivo, was observed by using B4GalT1 knocked down by lentivirus. Finally, the apoptosis and autophagy of glioblastoma was observed in vitro and in vivo. Results show that B4GalT1 was a highly variable gene, and GEPIA and TCGA systems show B4GalT1 expression in GBM tumor tissue was higher than in normal tissue. Pair-wise gene correlation analysis revealed a probable relationship between B4GalT1 and autophagy rel ated proteins. The B4GalT1 expression and mRNA level were increased in tumor cells, or U87 cells. B4GalT1 knocked down by lentivirus could inhibit glioblastoma development, in vitro and in vivo, by reducing tumor weight and volume, increasing survival, and weakening tumor cells proliferation, migration, invasion. B4GalT1 knockdown could increase apoptosis and autophagy of glioblastoma in vitro and in vivo. Our study demonstrates that B4GalT1 may be able to regulate apoptosis and autophagy of glioblastoma. Bax, Bcl-2, cleaved caspase-3, Beclin-1, and LC3 s may be the downstream target factors of B4GalT1 in apoptosis and autophagy, which may provide a new strategy to reduce glioblastoma development by regulating apoptosis and autophagy. PMID: 33287670 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles.

payth.elady61 shared this article with you from Inoreader Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles. Via pubmed: autophagy Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles. J Nanobiotechnology. 2020 Dec 07;18(1):178 Authors: Park DJ, Yun WS, Kim WC, Park JE, Lee SH, Ha S, Choi JS, Key J, Seo YJ Abstract BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSC-derived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules. RESULTS: The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We determined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation. CONCLUSIONS: It was concluded that the nanoparticles we developed were transported to the lysosome by clathrin-mediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors. PMID: 33287848 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Investigation of regulation and mechanism of miR-223 on autophagy of CD4 + T lymphocytes in septic mice.

payth.elady61 shared this article with you from Inoreader Investigation of regulation and mechanism of miR-223 on autophagy of CD4 + T lymphocytes in septic mice. Via pubmed: autophagy Investigation of regulation and mechanism of miR-223 on autophagy of CD4 + T lymphocytes in septic mice. Cell Mol Biol (Noisy-le-grand). 2020 Oct 31;66(7):207-215 Authors: Li Q, Xiang G, Peng C, Xie L, Ji W Abstract T-lymphocyte dysfunction is most important part of immune dysfunction in sepsis, where dynamic change, especially autophagy of CD4+T lymphocytes is found to be related to disease fate. Our study is to i nvestigate the changes of CD4 + T lymphocytes and their autophagy levels in septic miR-223 -/- mouse model injected intraperitoneally with E. coli.120 male C57BL/6J wild-type. Twenty male miR-223 knockout(miR-223-/-) mice were randomly divided into, according to intraperitoneal injection of normal saline (NS) and E. coli solution, normal saline (WT NS) group, sepsis (WT Sep) group, miR-223 -/- NS group and miR-223 -/- Sep group, respectively. The autophagy related protein was monitored with flow cytometry to observe the autophagy of CD4+T lymphocytes. Flow cytometry showed the proportion of CD4 + T lymphocytes in peripheral blood circulation, alveoli, and spleen of mice in the WT Sep group gradually decreased after surgery, the proportion of cells with autophagic activity in t his population of cells was significantly higher than that in the WT NS group, and the proportion of CD4 + T lymphocytes with active autophagic activity in miR-223 -/- mice were significantly decreased, but higher than that in the miR-223 -/- NS group and lower than the level of autophagy in CD4 + T cells of wild-type mice. Thus, miR-223 can up-regulate the level of autophagy in CD4 + T lymphocytes of septic mice, suggesting that miR-223 may be used as a potential target for the prevention and treatment of sepsis. PMID: 33287944 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Silencing ATG6 and PI3K accelerates petal senescence and reduces flower number and shoot biomass in petunia.

payth.elady61 shared this article with you from Inoreader Silencing ATG6 and PI3K accelerates petal senescence and reduces flower number and shoot biomass in petunia. Via pubmed: autophagy Silencing ATG6 and PI3K accelerates petal senescence and reduces flower number and shoot biomass in petunia. Plant Sci. 2021 Jan;302:110713 Authors: Lin Y, Jones ML Abstract Petal senescence is a form of developmental programmed cell death (PCD) that is regulated by internal and environmental signals. Autophagy, a metabolic pathway that regulates intercellular nutrient recycling, is thought to play an important role in the regulation of petal senescence-associated PCD. To characterize the function of two central autophagy genes in petal senescence, we down-regulated Autophagy Gene 6 (PhATG6) and Phosphoinositide 3-Kinase (PhPI3K) using Virus-Induced Gene Silencing (VIGS) in Petunia × hybrida. The silencing of PhATG6 and PhPI3K accelerated petal senescence, thereby reducing flower longevity. Both PhATG6- and PhPI3K-silenced petunias had reduced flower numbers, flower biomass, and vegetative shoot biomass. These phenotypes were intensified when plants were grown under low nutrient conditions. Additionally, two important regulators of senescence, an ethylene biosynthesis gene (PhACS) and a type I metacaspase gene (PhMC1), were suppressed in senesci ng petals of PhATG6- and PhPI3K-silenced plants. In conclusion, our study identified PhATG6 and PhPI3K as negative regulators of flower senescence and demonstrated the influence of nutrient limitation on the function of autophagy during petal senescence. Our study also found that autophagy genes potentially influence the transcriptional regulation of metacaspases and ethylene biosynthetic genes during petal senescence. The results of this project will be fundamental for future studies of petal senescence and will provide genetic information for future crop improvement. PMID: 33288020 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mir-139 Regulates Autophagy in Prostate Cancer Cells Through Beclin-1 and mTOR Signaling Proteins.

payth.elady61 shared this article with you from Inoreader Mir-139 Regulates Autophagy in Prostate Cancer Cells Through Beclin-1 and mTOR Signaling Proteins. Via pubmed: autophagy Mir-139 Regulates Autophagy in Prostate Cancer Cells Through Beclin-1 and mTOR Signaling Proteins. Anticancer Res. 2020 Dec;40(12):6649-6663 Authors: Nam RK, Benatar T, Amemiya Y, Sherman C, Seth A Abstract BACKGROUND/AIM: We previously identified a panel of five miRNAs (including miR-139) associated with biochemical recurrence and metastasis in prostate cancer patients. MATERIALS AND METHODS: We examined miR-139 transfected PC3, DU145 and LNCaP cells by morphology as well as by cell-based assays, confocal microscopy and immunoblotting. RESULTS: We found that treatment of prostate cancer cells with miR-139 resulted in phenotypic changes characteristic of autophagic cells. MiR-139 increased the autophagy-related conversion of the microtubule-associated protein light chain 3 (LC3-I to LC3-II) that was specifically inhibited by the miR-139 antagomir. The upregulation of LC3 II was further confirmed by confocal microscopy. miR-139 regulated activation of both mTOR and Beclin1 the two important autophagy-related molecules. We found that upon miR-139 treatment, the cargo adaptor protein p62 which is degraded during autophagy, accumulates. CONCLUSION: These results suggest that miR-139 is inducing autophagic flux blockade leading to apoptosis in prostate cancer cells through the mTOR and Beclin-1 proteins. PMID: 33288559 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Flavopereirine Inhibits Hepatocellular Carcinoma Cell Growth by Inducing Cell-cycle Arrest, Apoptosis, and Autophagy-related Protein Expression.

payth.elady61 shared this article with you from Inoreader Flavopereirine Inhibits Hepatocellular Carcinoma Cell Growth by Inducing Cell-cycle Arrest, Apoptosis, and Autophagy-related Protein Expression. Via pubmed: autophagy Flavopereirine Inhibits Hepatocellular Carcinoma Cell Growth by Inducing Cell-cycle Arrest, Apoptosis, and Autophagy-related Protein Expression. Anticancer Res. 2020 Dec;40(12):6907-6914 Authors: Chen SY, Chao CN, Huang HY, Fang CY Abstract BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Resistance to chemotherapy and side-effects remain a challenge for treating advanced and recurrent HCC. Therefore, there is an emerging need to develop new drugs to treat HCC. MATERIALS AND METHODS: We evaluated the anti-growth activity of flavopereirine in HepG2 and Huh7 HCC cell lines. Cell viability, cell-cycle profile, apoptosis, and autophagy-related protein expressions were analysed after flavopereirine treatment. RESULTS: Flavopereirine treatment induced G0/G1 cell-cycle arrest, with an increase of sub-G1 cells detected at the higher concentration and longer exposure to flavopereirine in HCC cells. Intrinsic and extrinsic pathways were involved in flavopereirine-induced apoptosis, as demonstrated by an increase of cleaved caspase 8 and 9 by western blotting. An alteration of autophagy-related protein expression was also found after flavopereirine treatment. CONCLUSION: Taken together, the current results indicate that flavopereirine exhibits good anticancer activity in HCC cells. PMID: 33288584 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Direct lysosome-based autophagy of lipid droplets in hepatocytes.

payth.elady61 shared this article with you from Inoreader Direct lysosome-based autophagy of lipid droplets in hepatocytes. Via pubmed: autophagy Direct lysosome-based autophagy of lipid droplets in hepatocytes. Proc Natl Acad Sci U S A. 2020 Dec 07;: Authors: Schulze RJ, Krueger EW, Weller SG, Johnson KM, Casey CA, Schott MB, McNiven MA Abstract Hepatocytes metabolize energy-rich cytoplasmic lipid droplets (LDs) in the lysosome-directed process of autophagy. An organelle-selective form of this process (macrolipophagy) results in the engulfment of LDs within double-membrane delimited structures (autophagosomes) before lysosomal fusion. Whether this is an exclusive autophagic mechanism used by hepatocytes to catabolize LDs is unclear. It is also unknown whether lysosomes alone might be sufficient to mediate LD turnover in the absence of an autophagosomal intermediate. We performed live-cell microscopy of hepatocytes to monitor the dynamic interactions between lysosomes and LDs in real-time. We additionally used a fluorescent variant of the LD-specific protein (PLIN2) that exhibits altered fluorescence in response to LD interactions with the lysosome. We find that mammalian lysosomes and LDs undergo interactions during which proteins and lipids can be transferred from LDs directly into lysosomes. Electron microscopy (EM ) of primary hepatocytes or hepatocyte-derived cell lines supports the existence of these interactions. It reveals a dramatic process whereby the lipid contents of the LD can be "extruded" directly into the lysosomal lumen under nutrient-limited conditions. Significantly, these interactions are not affected by perturbations to crucial components of the canonical macroautophagy machinery and can occur in the absence of double-membrane lipoautophagosomes. These findings implicate the existence of an autophagic mechanism used by mammalian cells for the direct transfer of LD components into the lysosome for breakdown. This process further emphasizes the critical role of lysosomes in hepatic LD catabolism and provides insights into the mechanisms underlying lipid homeostasis in the liver. PMID: 33288726 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Strongylocentrotus nudos Egg Polysaccharide induces autophagy and apoptosis in leukaemia cells by regulating mitochondrial function.

payth.elady61 shared this article with you from Inoreader Strongylocentrotus nudos Egg Polysaccharide induces autophagy and apoptosis in leukaemia cells by regulating mitochondrial function. Via pubmed: autophagy Strongylocentrotus nudos Egg Polysaccharide induces autophagy and apoptosis in leukaemia cells by regulating mitochondrial function. J Cell Mol Med. 2020 Dec 01;: Authors: Wang C, Li M, Li L, Shen X, Liu Y, Wang S Abstract In this study, we investigated the ability of the Polysaccharide from the Eggs of Strongylocentrotus nudus (SEP) to regulate cellular autophagy and apoptosis in leukaemia cells. Human acute myeloid leukaemia (AML) cells (HL60) and murine AML cells (L1210) treated with SEP were used to assess viability using Cell Counting Kit-8, cytotoxicity by measuring lactate dehydrogenase release, the generation of reactive oxygen species (ROS) by DCFH-DA staining. In addition, we utilized a mouse model of leukaemia in which L1210 cells were injected into DBA/2 mice by sub-axillary injection. Treatment with SEP decreased cell viability, increased in cytotoxicity and increased the release of ROS in a dose-dependent manner. SEP treatment was also associated with the activation of pro-apoptotic proteins cleaved caspase-3, cleaved caspase-9 and cleaved poly (ADP-ribose) polymerase (PARP). Activation of the apoptotic pathway led to the release of cytochrome C (CytoC) into the cytosol of the cel l resulting in decreased membrane potential. The effect of SEP treatment was depended on the activation of the nuclear factor kappa-B (NF-κB) signalling pathway as SEP treatment led to an increase in NF-κB phosphorylation, and inhibition of NF-κB signalling using PDTC blocked SEP-mediated activation of apoptosis. Treatment with SEP also prolonged survival time in our leukaemia mouse model and was associated with diminished tumour volume, increased leucocyte and lymphocyte proliferation, promoted pro-inflammatory factor release in serum and enhanced immune function. Taken together, these data suggest that SEP inhibits the progression of leukaemia by initiating mitochondrial dysfunction, autophagy, and apoptosis via the NF-κB signalling pathway. PMID: 33289295 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tetrahedral Framework Nucleic Acid Inhibits Chondrocyte Apoptosis and Oxidative Stress through Activation of Autophagy.

payth.elady61 shared this article with you from Inoreader Tetrahedral Framework Nucleic Acid Inhibits Chondrocyte Apoptosis and Oxidative Stress through Activation of Autophagy. Via pubmed: autophagy Tetrahedral Framework Nucleic Acid Inhibits Chondrocyte Apoptosis and Oxidative Stress through Activation of Autophagy. ACS Appl Mater Interfaces. 2020 Dec 08;: Authors: Shi S, Tian T, Li Y, Xiao D, Zhang T, Gong P, Lin Y Abstract Osteoarthritis (OA) is a degenerative articular cartilage pathogenic process that is accompanied by excessive chondrocyte apoptosis. The occurrence of chondrocyte death and OA is related to decreased autophagy. Tetrahedral framework nucleic acid (TFNA), a potent bioactive DNA nanomaterial, exerts antiapoptotic and antioxidative effects in various diseases, resulting in autophagy promotion and inhibition of the Wnt/β-catenin-signaling pathway. Here, we aimed to elucidate the therapeutic effects of TFNA on OA and its potential molecular mechanism of action. TFNA was synthesized and characterized by established methods. An interleukin (IL)-1β stimulated OA cell model was established and treated with TFNA. Cellular uptake of TFNA and intracellular reactive oxygen species levels were examined via immunofluorescence and flow cytometry. Apoptotic cell death was documented by the Cell Counting Kit-8 (CCK8) assay and flow cytometry. Transmission electron microscopy was applied to vi ew the autophagosomes. The expression of BCL2, BAX, caspase-3, Nrf2, HO-1, LC3-II, Beclin1, Atg7, β-catenin, Lef-1, and CyclinD1 was detected by immunofluorescence and western blotting. TFNA was successfully synthesized and effectively entered chondrocytes in the absence or presence of IL-1β without the help of transfection agents. TFNA treatment in IL-1β-induced chondrocytes reduced apoptosis by activating the BCL2/BAX/caspase-3 pathway, inhibited oxidative stress by regulating the Nrf2/HO-1-signaling pathway, and enhanced autophagy through upregulated LC3-II, Beclin1, and Atg7. Moreover, TFNA showed chondroprotective effects by regulating the Wnt/β-catenin-signaling pathway. Overall, TFNA may have utility as a therapeutic nanomedicine for OA. PMID: 33289541 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Autophagy-mediated regulation patterns contribute to the alterations of the immune microenvironment in periodontitis.

payth.elady61 shared this article with you from Inoreader Autophagy-mediated regulation patterns contribute to the alterations of the immune microenvironment in periodontitis. Via pubmed: autophagy Autophagy-mediated regulation patterns contribute to the alterations of the immune microenvironment in periodontitis. Aging (Albany NY). 2020 Dec 03;12: Authors: Zhang X, Jin Y, Wang Q, Jian F, Li M, Long H, Lai W Abstract The relationship between autophagy and immunity has been thoroughly investigated. However, little is known about the role of autophagy in shaping the immune-microenvironment of periodontitis. Thus, we aim to explore the impact of autophagy on the immune-microenvironment of periodontitis. The expression distinctions of autophagy genes between healthy and periodontitis samples have been investigated. The connections between autophagy and immune characteristics including infiltrating immunocyte, immune reaction and human leukocyte antigen (HLA) gene were evaluated. The distinct autophagy-mediated expression patterns were identified and immune characteristics under distinct patterns were revealed. Autophagy phenotype-related genes were identified. 16 autophagy genes were dysregulated and a ten-autophagy classifier was constructed that can well distinguish periodontitis and healthy samples. Immune characteristics were closely related to autophagy: higher expression of EDEM1 positi vely relates to infiltrating activated B cell; NCKAP1 negatively relates to monocyte; CXCR4 enhances BCR Signaling Pathway and PEX3 decreases the activity of TNF Family Members Receptors; positive expression correlation of EDEM1-HLADOB and negative correlation of RAB11A-HLADOB were observed. Two distinct autophagy expression patterns were identified which demonstrated different immune characteristics. 4309 autophagy phenotype-related genes were identified, and 219 of them were related to immunity, whose biological functions were found to be involved in immunocyte regulations. Our study revealed the strong impact of autophagy on the immune-microenvironment of periodontitis and brought new insights into the understanding of the pathogenesis of periodontitis. PMID: 33289699 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Atorvastatin improves motor function, anxiety and depression by NOX2-mediated autophagy and oxidative stress in MPTP-lesioned mice.

payth.elady61 shared this article with you from Inoreader Atorvastatin improves motor function, anxiety and depression by NOX2-mediated autophagy and oxidative stress in MPTP-lesioned mice. Via pubmed: autophagy Atorvastatin improves motor function, anxiety and depression by NOX2-mediated autophagy and oxidative stress in MPTP-lesioned mice. Aging (Albany NY). 2020 Dec 03;12: Authors: Yan J, Huang J, Liu A, Wu J, Fan H, Shen M, Lai X, Ma H, Sun W, Yang J, Xu Y Abstract Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. It is characterized by static tremors, stiffness, slow movements, and gait disturbances, but it is also accompanied by anxiety and depression. Our previous study showed that atorvastatin could reduce the risk of PD, but the mechanism is still unclear. In this paper, Our findings showed that atorvastatin increased muscle capacity and the coordination of movement and improved anxiety and depression. Atorvastatin could decrease the expression of α-synuclein Ser129 and NADPH oxidase 2 (NOX2), increase the protein expression of LC3II/I, and promote autophagy flow. To further confirm that atorvastatin protection was achieved by inhibiting NOX2, we injected at midbrain with NOX2 shRNA (M) lentivirus and found that silent NOX2 produced the same effect as atorvastatin. Further research found that atorvastatin could reduce MPTP-induced oxidative stress damage, while inhibiting NOX2 decr eased the antioxidative stress effect of atorvastatin. Our results suggest that atorvastatin can improve muscle capacity, anxiety and depression by inhibiting NOX2, which may be related to NOX2-mediated oxidative stress and autophagy. Atorvastatin may be identified as a drug that can effectively improve behavioral disorders. NOX2 may be a potential gene target for new drug development in PD. PMID: 33289703 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.