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Seul-Gi Lee, Young Ae Joe
Mesenchymal stromal/stem cells (MSCs) have been promising source for regenerative cell therapy in ischemic diseases. To improve efficacy of MSC therapy, various priming methods have been developed, and hypoxic priming has been reported to enhance therapeutic efficacy of MSCs by increasing secretion level of growth factors and cytokines. Recently, it has been reported that bone marrow MSCs primed with hypoxic condition show an increase of autophagy. Here, we addressed whether proangiogenic activity increased by hypoxic condition is associated with autophagy...
May 14, 2018: Biochemical and Biophysical Research Communications
Xin Fang, Keli Ge, Chao Song, Yin Lin-Ge, Jin Yu-Zhang
OBJECTIVE: Fat-1 transgenic mice were used as a model to study the effect of endogenous n-3 polyunsaturated fatty acids (n-3PUFAs) on the body weight, inflammatory factors and autophagy proteins in hypothalamus to explore the mechanism of n-3PUFAs inhibiting obesity. METHOD: The mice were divided into two groups after genotype identification: fat-1 transgenic mice and wild-type mice. The body weight and body length of mice were measured at 14th week, and calculated the Lee 's index...
May 14, 2018: Biochemical and Biophysical Research Communications
Li Meng, Sabrina Z Jan, Geert Hamer, Ans M van Pelt, Inge van der Stelt, Jaap Keijer, Katja J Teerds
There is general agreement that granulosa cell apoptosis is the cause of antral follicle attrition. Less clear is whether this pathway is also activated in case of preantral follicle degeneration, as several reports mention that the incidence of granulosa cell apoptosis in preantral follicles is negligible. Our objective is therefore to determine which cell-death pathways are involved in preantral and antral follicular degeneration.Atretic preantal and antral follicles were investigated using immunohistochemistry and laser-capture micro-dissection followed by qRT-PCR...
May 14, 2018: Biology of Reproduction
Joseph Robert Burgoyne
Dysfunctional macroautophagy/autophagy has been causatively linked to aging and the pathogenesis of many diseases, which are also broadly characterized by dysregulated cellular redox. As the autophagy-related (ATG) conjugation systems that mediate autophagosome maturation are cysteine dependent, their oxidation may account for loss in this catabolic process under conditions of oxidative stress. During active autophagy, LC3 is transferred from the catalytic thiol of ATG7 to the active site thiol of ATG3, where it is conjugated to phosphatidylethanolamine...
May 10, 2018: Autophagy
Dong Chen, Junyi Chen, Yihong Guo, Yining Li
The effects of cinobufacini on apoptosis of human bladder cancer T24 cells and the expression of autophagy-related genes and proteins were studied. The human bladder cancer T24 cells were selected, and the inhibitory effect of cinobufacini on the proliferation of human bladder cancer cells was detected by cell viability assay. Flow cytometry and Hoechst staining were used to detect the changes in the apoptosis of bladder cancer cells after being treated with cinobufacini; the changes in the expression levels of human bladder cancer cell apoptosis-related genes and proteins, cleaved caspase-3, Bax, B-cell lymphoma-2 (Bcl-2) and autophagy-related genes and proteins, p62, light chain 3 (LC3) and autophagy-related protein 7 (Atg7) after treatment with cinobufacini were detected by western blot analysis and reverse transcription polymerase chain reaction (RT-PCR)...
May 2018: Oncology Letters
Peihua Luo, Yi Zhu, Min Chen, Hao Yan, Bo Yang, Xiaochun Yang, Qiaojun He
Adriamycin (ADR) is one of the most widely used and effective anthracycline antitumor agents in the treatment of certain hematological malignancies and solid tumors. However, the severe cardiotoxicity of ADR limits its clinical application. So far, the mechanism of the cardiotoxicity of ADR has not been completely clarified. In our research, cardiomyocyte autophagy and cardiac damage were observed in accompany ADR treatment, and autophagy appeared earlier than cardiac damage. Inhibition of autophagy by silencing ATG7 improved the survival rate of cardiomyocytes treated with ADR...
April 28, 2018: Toxicology Letters
Wenting Cao, Ge Qian, Wen Luo, Xin Liu, Yunjing Pu, Guilan Hu, Lulu Han, Limei Yuan, Xiao A, Danqi Deng
Systemic lupus erythematosus (SLE) is a severe autoimmune disease and the pathogenesis remains incompletely understood. This study aimed to investigate the role of miR-125b in the pathogenesis of SLE and explore the underlying mechanism. Compared to healthy controls, the expression of miR-125b decreased in peripheral blood mononuclear cells (PBMCs) of SLE patients. In addition, PBMCs exposed to ultraviolet B had lower miR-125b level compared to those unexposed to radiation. We identified UV radiation resistance associated gene (UVRAG) as a target of miR-125b...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ja Yeon Kim, Jing-Hsiung James Ou
Apolipoprotein E (ApoE) plays an important role in the maturation and infectivity of hepatitis C virus (HCV). By analyzing the subcellular localization of ApoE in Huh7 hepatoma cells that harbored an HCV subgenomic RNA replicon, we found that ApoE colocalized with autophagosomes. This colocalization was marginally detected in HCV-infected cells apparently due to the depletion of ApoE by HCV, as the treatment with bafilomycin A1 (BafA1), a vacuolar ATPase inhibitor that inhibits autophagic protein degradation, partially restored the ApoE level and enhanced its colocalization with autophagosomes in HCV-infected cells...
April 25, 2018: Journal of Virology
Yamei Sun, Qunchao Bao, Baoqin Xuan, Wenjia Xu, Deng Pan, Qi Li, Zhikang Qian
Human cytomegalovirus (HCMV) protein pUL38 has been shown to prevent premature cell death by antagonizing cellular stress responses; however, the underlying mechanism remains unknown. In this study, we identified the host protein ubiquitin-specific protease 24 (USP24) as an interaction partner of pUL38. Mutagenesis analysis of pUL38 revealed that amino acids TFV at 227-230 were critical for its interaction with USP24. Mutant pUL38 TFV/AAA protein did not bind to USP24 and failed to prevent cell death induced by pUL38-deficient HCMV infection...
April 25, 2018: Journal of Virology
Hai Huang, Chao Wang, Fei Liu, Hui-Zhen Li, Guang Peng, Xu Gao, Ke-Qin Dong, Hong-Ru Wang, De-Pei Kong, Min Qu, Li-He Dai, Kai-Jian Wang, Zhe Zhou, Jun Yang, Ze-Yu Yang, Yan-Qiong Cheng, Qin-Qin Tian, Dan Liu, Chuan-Liang Xu, Dan-Feng Xu, Xin-Gang Cui, Ying-Hao Sun
PURPOSE: Cancer stem-like cells (CSCs) contribute to the progression and androgen deprivation therapy (ADT) resistance of prostate cancer. Since CSCs depend on their specific niche, including tumor-associated macrophages (TAMs), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer. EXPERIMENTAL DESIGN: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA-seq, co-IP, ChIP and other assays...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yingliang Ou, Jiafa He, Yubin Liu
The miR-490-3p was transfected into HepG2 cells to explore the correlation between miR-490-3p and hepatocellular carcinoma cell proliferation, apoptosis, and autophagy and its downstream target gene ATG7. Then we could possibly provide a mechanism for the treatment of hepatocellular carcinoma. MiR-490-3p was screened out by fold change > 4 and P < 0.01 using gene microarray data. The expression level of miR-490-3p was tested by qRT-PCR and the prognosis analysis was achieved by using TCGA data...
April 20, 2018: IUBMB Life
Juan Zhong, Wangqiu Gong, Jing Chen, Yao Qing, Shuyue Wu, Hongbei Li, Chunxi Huang, Yihua Chen, Yuxian Wang, Zhaozhong Xu, Wenting Liu, HongYu Li, Haibo Long
The anti-inflammatory, immunomodulatory, and anticancer effects of micheliolide (MCL) isolated from Michelia champaca were previously reported, but its role and underlying mechanisms in relieving liver steatosis remain unclear. Herein, we investigated the effects of MCL on hepatic steatosis using a db/db mouse model and lipid mixture (LM)-induced AML12 and LO2 cells. The body and liver weights, food consumption, lipid content and liver aminotransferase levels in serum, the lipid content and inflammatory cytokine levels in liver tissue, and the extent of hepatic steatosis in db/db mice were increased compared with those in db/m mice, and these increases were reversed by MCL treatment...
April 12, 2018: International Immunopharmacology
Alyssa Walker, Anju Singh, Ellen Tully, Juhyung Woo, Anne Le, Tu Nguyen, Shyam Biswal, Dipali Sharma, Edward Gabrielson
Autophagy can serve as a mechanism for survival of cells during nutrient deprivation by recycling cellular macromolecules and organelles transiently to provide essential metabolic substrates. However, autophagy itself causes metabolic stress to cells, and other cellular protective mechanisms likely cooperate with autophagy to promote cell survival during nutrient deprivation. In this study, we explored protective mechanisms in breast cancer cells in the setting of glucose deprivation. While breast cancer cells (MCF7 and T47D) survive in glucose-free medium for three days or more, autophagy is induced in this setting...
April 9, 2018: Free Radical Biology & Medicine
Shumin Zhou, Qiang Hong, Yang Li, Qi Li, Mao Wang
Programmed cell death (PCD) and autophagy are both important means for plants to resist pathogen. It is also the main biological reaction of plant immunity. In previous studies, we found that TMV local-infection on tomato leaves not only caused the PCD process in the distal root tissues, but also induced autophagy in root-tip cells. However, the reasons for these biological phenomena are unclear. In order to get deeper insight, the role of a putative inducible factor reactive oxidative species (ROS) was investigated...
April 2018: Plant Science: An International Journal of Experimental Plant Biology
A Srivastava, S Singh, C S Rajpurohit, P Srivastava, A Pandey, D Kumar, V K Khanna, A B Pant
A perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell-cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many health hazards. We, therefore, explored the protective efficacy of the secretome of differentiated PC12 cells with emphasis on induction of autophagy and mitochondrial biogenesis...
March 30, 2018: Neuromolecular Medicine
Sei Sai, Masao Suzuki, Eun Ho Kim, Mitsuhiro Hayashi, Guillaume Vares, Naoyoshi Yamamoto, Tadaaki Miyamoto
Malignant mesothelioma (MM) is extremely aggressive and a typical refractory cancer. In this study we investigated how effective on killing MM cells by carbon ion beam alone or in combination with cisplatin (CDDP) in vitro . Carbon ion beam (at the center of SOBP with 50 keV/µm of average LET) dose-independently suppressed MM cells MESO-1 and H226 cell viability and in combination with CDDP (25 μM) significantly enhanced its action. Relative biological effectiveness (RBE) values at 73 keV/μm and 13 keV/μm portion of carbon ion beam was estimated as 2...
March 13, 2018: Oncotarget
Ana Santos-Llamas, Maria J Monte, Jose J G Marin, Maria J Perez
The nucleoside reverse transcriptase inhibitor zidovudine (AZT), used in HIV infection treatment, induces mitochondrial DNA (mtDNA) depletion. A cause-effect relationship between mtDNA status alterations and autophagy has been reported. Both events are common in several liver diseases, including hepatocellular carcinoma. Here, we have studied autophagy activation in rat liver with mtDNA depletion induced by AZT administration in drinking water for 35 days. AZT at a concentration of 1 mg/ml, but not 0.5 mg/ml in the drinking water, decreased mtDNA levels in rat liver and extrahepatic tissues...
March 28, 2018: Archives of Toxicology
Lucía Sanjurjo, Gemma Aran, Érica Téllez, Núria Amézaga, Carolina Armengol, Daniel López, Clara Prats, Maria-Rosa Sarrias
CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes...
2018: Frontiers in Immunology
Junchao Cai, Rong Li, Xiaonan Xu, Le Zhang, Rong Lian, Lishan Fang, Yongbo Huang, Xianming Feng, Ximeng Liu, Xu Li, Xun Zhu, Heng Zhang, Jueheng Wu, Musheng Zeng, Erwei Song, Yukai He, Yuxin Yin, Jun Li, Mengfeng Li
The contribution of autophagy to cancer development remains controversial, largely owing to the fact that autophagy can be tumour suppressive or oncogenic in different biological contexts. Here, we show that in non-small-cell lung cancer (NSCLC), casein kinase 1 alpha 1 (CK1α) suppresses tumour growth by functioning as an autophagy inducer to activate an autophagy-regulating, tumour-suppressive PTEN/AKT/FOXO3a/Atg7 axis. Specifically, CK1α bound the C-terminal tail of PTEN and enhanced both PTEN stability and activity by competitively antagonizing NEDD4-1-induced PTEN polyubiquitination and abrogating PTEN phosphorylation, thereby inhibiting AKT activity and activating FOXO3a-induced transcription of Atg7...
April 2018: Nature Cell Biology
Tsung-Chang Tsai, Kuei-Hung Lai, Jui-Hsin Su, Yu-Jen Wu, Jyh-Horng Sheu
The 7-Acetylsinumaximol B (7-AB), a bioactive cembranoid, was originally discovered from aquaculture soft coral Sinularia sandensis . The current study investigated the anti-proliferative property of 7-AB towards the NCI-N87 human gastric cancer cell line. An MTT cell proliferative assay was applied to evaluate cell survival, and immunofluorescence staining and western blotting were employed to analyze the effects of 7-AB on autophagy and apoptosis. Our results showed that 7-AB exerted a concentration-dependent anti-proliferative effect on NCI-N87 cells, and fluorescence staining indicated that the effect was due to the apoptosis induced by 7-AB...
March 26, 2018: Marine Drugs
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