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  • 1
    Language: English
    In: Nature communications, 2017-03-22, Vol.8 (1), p.14846-14846
    Description: Acetylation of Atg3 regulates the lipidation of the protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe the first semi-synthesis of homogeneous K19/K48-diacetylated Atg3 through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with the semi-synthetic proteins confirm that Atg3 acetylation can promote the lipidation of Atg8. We find that acetylation of Atg3 enhances its binding to phosphatidylethanolamine-containing liposomes and to endoplasmic reticulum, through which it promotes the lipidation process.
    ISSN: 2041-1723
    E-ISSN: 2041-1723
    Source: Nature Open Access
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 2
    Language: English
    In: Nature communications, 2018-03-21, Vol.9 (1), p.1165-13
    Description: Cleavage of transfer (t)RNA and ribosomal (r)RNA are critical and conserved steps of translational control for cells to overcome varied environmental stresses. However, enzymes that are responsible for this event have not been fully identified in high eukaryotes. Here, we report a mammalian tRNA/rRNA-targeting endoribonuclease: SLFN13, a member of the Schlafen family. Structural study reveals a unique pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N'-domain that may clamp base-paired RNAs. SLFN13 is able to digest tRNAs and rRNAs in vitro, and the endonucleolytic cleavage dissevers 11 nucleotides from the 3'-terminus of tRNA at the acceptor stem. The cytoplasmically localised SLFN13 inhibits protein synthesis in 293T cells. Moreover, SLFN13 restricts HIV replication in a nucleolytic activity-dependent manner. According to these observations, we term SLFN13 RNase S13. Our study provides insights into the modulation of translational machinery in high eukaryotes, and sheds light on the functional mechanisms of the Schlafen family.
    Subject(s): Binding Sites ; Cleavage ; Cloning, Molecular ; Crystallography, X-Ray ; Cytoplasm - chemistry ; Cytoplasm - enzymology ; Cytoplasm - virology ; Endoribonucleases - chemistry ; Endoribonucleases - genetics ; Endoribonucleases - metabolism ; Environmental stress ; Escherichia coli - genetics ; Escherichia coli - metabolism ; Eukaryotes ; Gene Expression ; Genetic Vectors ; HEK293 Cells ; HIV ; HIV-1 - genetics ; HIV-1 - growth & development ; Human immunodeficiency virus ; Humans ; Kinetics ; Machinery ; Models, Molecular ; Nucleotides ; Protein Binding ; Protein Biosynthesis ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; Protein Interaction Domains and Motifs ; Protein synthesis ; Recombinant Proteins - chemistry ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Ribonuclease ; Ribonucleic acid ; RNA ; RNA Cleavage ; RNA, Ribosomal - chemistry ; RNA, Ribosomal - genetics ; RNA, Ribosomal - metabolism ; RNA, Transfer - chemistry ; RNA, Transfer - genetics ; RNA, Transfer - metabolism ; rRNA ; Substrate Specificity ; Translation ; tRNA ; Virus Replication
    ISSN: 2041-1723
    E-ISSN: 2041-1723
    Source: Nature Open Access
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 3
    Language: English
    In: PloS one, 2018, Vol.13 (5), p.e0198027-e0198027
    Description: β2-microglobulin (B2M), the light chain of major histocompatibility complex class I (MHC I) molecules, has been found to impair hippocampal neurogenesis. Based on the crucial role of hippocampal neurogenesis disturbance in the process of depression and anxiety, the aim of the present study is to investigate whether B2M leads to depressive- and anxiety-like behaviors. We found that 6 days after intracerebroventricular injection with B2M (0.3 μg), the immobility times of rats in the tail suspension test and the forced swimming test were increased, the swimming and climbing time in the forced swimming test was decreased, and the latency to feed in the novelty-suppressed feeding test was increased, indicating that B2M induces depressive-like behaviors. In addition, in the elevated plus maze test, B2M-treated rats displayed obvious decline in the number of entries into and the proportion of time spent in the open arm, while the number of total arm entries was no change, which indicated that B2M induces anxiety-like behaviors. Our present findings suggest that target B2M might represent a novel approach for treatment of depression and anxiety.
    Subject(s): Animals ; Antidepressants ; Anxieties ; Anxiety ; Anxiety Disorders - etiology ; Anxiety Disorders - pathology ; Behavior ; Behavior, Animal ; beta 2-Microglobulin - adverse effects ; Biology and Life Sciences ; Brain ; Depressive Disorder - etiology ; Depressive Disorder - pathology ; Disease Models, Animal ; Hippocampus ; Hospitals ; Laboratory animals ; Latency ; Major histocompatibility complex ; Male ; Medicine and Health Sciences ; Mental depression ; Molecular chains ; Neurogenesis ; Neurology ; Neurosciences ; Physiology ; Psychopharmacology ; Rats ; Rats, Sprague-Dawley ; Research and Analysis Methods ; Rodents ; Studies ; Swimming
    ISSN: 1932-6203
    E-ISSN: 1932-6203
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 4
    Language: English
    In: Nature communications, 2020-06-26, Vol.11 (1), p.3232-12
    Description: CRISPR-Cas9 has emerged as a powerful technology that relies on Cas9/sgRNA ribonucleoprotein complexes (RNPs) to target and edit DNA. However, many therapeutic targets cannot currently be accessed due to the lack of carriers that can deliver RNPs systemically. Here, we report a generalizable methodology that allows engineering of modified lipid nanoparticles to efficiently deliver RNPs into cells and edit tissues including muscle, brain, liver, and lungs. Intravenous injection facilitated tissue-specific, multiplexed editing of six genes in mouse lungs. High carrier potency was leveraged to create organ-specific cancer models in livers and lungs of mice though facile knockout of multiple genes. The developed carriers were also able to deliver RNPs to restore dystrophin expression in DMD mice and significantly decrease serum PCSK9 level in C57BL/6 mice. Application of this generalizable strategy will facilitate broad nanoparticle development for a variety of disease targets amenable to protein delivery and precise gene correction approaches.
    Subject(s): Animals ; Biomedical engineering ; Cations ; CRISPR ; CRISPR-Associated Protein 9 - metabolism ; CRISPR-Cas Systems - genetics ; CRISPR-Cas9 genome editing ; Deoxyribonucleic acid ; DNA ; DNA, Neoplasm - isolation & purification ; Drug delivery ; Dystrophin ; Dystrophin - genetics ; Gene delivery ; Gene Editing ; Genes ; Genetic modification ; Genomes ; HeLa Cells ; Humans ; Intravenous administration ; Lipids ; Lipids - chemistry ; Lungs ; Mice, Inbred C57BL ; Muscles ; Nanoparticles ; Nanoparticles - chemistry ; Nucleic-acid therapeutics ; Organ Specificity - genetics ; Proteins ; Ribonucleoproteins ; Ribonucleoproteins - metabolism ; Therapeutic applications ; Tissues
    ISSN: 2041-1723
    E-ISSN: 2041-1723
    Source: Nature Open Access
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 5
    Language: English
    In: Advanced functional materials, 2017-03-24, Vol.27 (12), p.1605352-n/a
    Description: Bioprinting is the most convenient microfabrication method to create biomimetic three-dimensional (3D) cardiac tissue constructs, that can be used to regenerate damaged tissue and provide platforms for drug screening. However, existing bioinks, which are usually composed of polymeric biomaterials, are poorly conductive and delay efficient electrical coupling between adjacent cardiac cells. To solve this problem, a gold nanorod (GNR)-incorporated gelatin methacryloyl (GelMA)- based bioink is developed for printing 3D functional cardiac tissue constructs. The GNR concentration is adjusted to create a proper microenvironment for the spreading and organization of cardiac cells. At optimized concentrations of GNR, the nanocomposite bioink has a low viscosity, similar to pristine inks, which allows for the easy integration of cells at high densities. As a result, rapid deposition of cell-laden fibers at a high resolution is possible, while reducing shear stress on the encapsulated cells. In the printed GNR constructs, cardiac cells show improved cell adhesion and organization when compared to the constructs without GNRs. Furthermore, the incorporated GNRs bridge the electrically resistant pore walls of polymers, improve the cell-to-cell coupling, and promote synchronized contraction of the bioprinted constructs. Given its advantageous properties, this gold nanocomposite bioink may find wide application in cardiac tissue engineering.
    Subject(s): Alginate ; Bioengineering ; Biological products ; Biomedical materials ; Biomimetics ; Bioprinting ; Bridge construction ; Bridges ; Cardiac tissue engineering ; Cell adhesion ; Cell adhesion & migration ; Construction contracts ; Coupling ; Damage ; Electrical resistivity ; Encapsulation ; Gelatin ; Gelatins ; Gold ; Gold nanorods ; High resolution ; Inks ; IR-102934 ; METIS-320709 ; Nanocomposites ; Nanorods ; Nanostructure ; Polymers ; Printing ; Shear stress ; Stress concentration ; Surgical implants ; Three dimensional printing ; Tissue engineering ; Viscosity
    ISSN: 1616-301X
    E-ISSN: 1616-3028
    Source: Hellenic Academic Libraries Link
    Source: Alma/SFX Local Collection
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  • 6
    Language: English
    In: International journal of biological sciences, 2012, Vol.8 (2), p.272-288
    Description: Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-β/BMPs is specifically through both canonical Smad-dependent pathways (TGF-β/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-β/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-β/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-β/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-β/BMP signaling. This review also highlights the different modes of cross-talk between TGF-β/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation.
    Subject(s): Animals ; BMP signaling ; Bone ; Bone Morphogenetic Proteins - metabolism ; Cell Differentiation ; Gene Expression Regulation - physiology ; Humans ; Mice ; Osteoblasts ; Osteoblasts - cytology ; Osteoblasts - physiology ; Osteogenesis - physiology ; Review ; Runx2 ; Signal Transduction ; Smad ; TGF signaling ; Transforming Growth Factor beta - metabolism
    ISSN: 1449-2288
    E-ISSN: 1449-2288
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 7
    Language: English
    In: Cell research, 2013, Vol.23 (11), p.1270-1283
    Description: The vagus nerve can control inflammatory response through a 'cholinergic anti-inflammatory pathway', which is mediated by the α7-nicotinic acetylcholine receptor (α7nAChR) on macrophages. However, the intracellular mechanisms that link a7nAChR activation and pro-inflammatory cytokine production remain not well understood. In this study, we found that miR-124 is upregulated by cholinergic agonists in LPS-exposed cells and mice. Utilizing miR-124 mimic and siRNA knockdown, we demonstrated that miR-124 is a critical mediator for the cholinergic anti-inflammatory action. Furthermore, our data indicated that miR-124 modulates LPS-induced cytokine production by targeting signal transducer and activator of transcription 3 (STAT3) to decrease IL-6 production and TNF-o converting enzyme (TACE) to reduce TNF-α release. These results also indicate that miR-124 is a potential therapeutic target for the treatment of inflammatory diseases.
    Subject(s): Acetylcholine receptors ; ADAM Proteins - metabolism ; ADAM17 Protein ; alpha7 Nicotinic Acetylcholine Receptor - metabolism ; Animals ; Cells, Cultured ; cholinergic anti-inflammatory action ; Cholinergic Neurons - metabolism ; Cytokines - biosynthesis ; Cytokines - genetics ; Cytokines - secretion ; HEK293 Cells ; Humans ; Interleukin-6 - biosynthesis ; Interleukin-6 - genetics ; Lipopolysaccharides - antagonists & inhibitors ; Lipopolysaccharides - pharmacology ; macrophages ; Macrophages - metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; micorRNA-124 ; MicroRNAs - metabolism ; Original ; Sepsis - chemically induced ; Sepsis - genetics ; Sepsis - metabolism ; Sepsis - pathology ; septic shock ; siRNA ; STAT3 ; STAT3 Transcription Factor - metabolism ; TACE ; TNF-α ; Transcription, Genetic ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor Necrosis Factor-alpha - genetics ; α7nAChR ; 乙酰胆碱受体 ; 抗炎作用 ; 细胞因子 ; 胆碱能
    ISSN: 1001-0602
    E-ISSN: 1748-7838
    Source: Nature Journals Online
    Source: PubMed Central
    Source: Alma/SFX Local Collection
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  • 8
    Language: English
    In: Chemical reviews, 2014-07-23, Vol.114 (14), p.7268-7316
    Description:   Li and Yu examine new stories of zeolite structures with regard to their descriptions, determinations, predictions, and evaluations.
    Subject(s): Chemical properties ; Crystallization ; Descriptions ; Lithium ; Research ; Zeolites
    ISSN: 0009-2665
    E-ISSN: 1520-6890
    Source: Hellenic Academic Libraries Link
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  • 9
    Language: English
    In: Acta pharmacologica Sinica, 2017, Vol.38 (2), p.157-167
    Description: It has been widely recognized that inflammation, particularly chronic inflammation, can increase the risk of cancer and that the simultaneous treatment of inflammation and cancer may produce excellent therapeutic effects. Berberine, an alkaloid isolated from Rhizoma coptidis, has broad applications, particularly as an antibacterial agent in the clinic with a long history. Over the past decade, many reports have demonstrated that this natural product and its derivatives have high activity against both cancer and inflammation In this review, we sqmmarize the advances in studing berberine and its derivatives as anti-inflammatory and anti-tumor agents in the digestive system; we also discuss their structure-activity relationship. These data should be useful for the development of this natural product as novel anticancer drugs with anti-inflammation activity.
    Subject(s): Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; anti-inflammatory drug ; anticancer drug ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; berberine ; Berberine - analogs & derivatives ; Berberine - pharmacology ; Berberine - therapeutic use ; digestive system ; Digestive System - drug effects ; Humans ; natural product ; Review ; Structure-Activity Relationship ; 天然产物 ; 小檗碱 ; 慢性炎症 ; 抗炎活性 ; 抗肿瘤作用 ; 治疗效果 ; 消化系统 ; 衍生物
    ISSN: 1671-4083
    E-ISSN: 1745-7254
    Source: PubMed Central
    Source: Alma/SFX Local Collection
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  • 10
    Language: English
    In: Cell transplantation, 2020-09-09, Vol.29, p.963689720958656-963689720958656
    Description: 8-Chloro-adenosine (8-Cl-Ado) has been shown to exhibit its antitumor activity by inducing apoptosis in human lung cancer A549 and H1299 cells or autophagy in chronic lymphocytic leukemia, and MDA-MB-231 and MCF-7 breast cancer cells. Adenosine deaminases acting on RNA 1 (ADAR1) is tightly associated with cancer development and progression. The aim of this study was to investigate the role of ADAR1 in the proliferation of MDA-MB-231 and SK-BR-3 breast cancer cell lines after 8-Cl-Ado exposure and its possible mechanisms. After 8-Cl-Ado exposure, CCK-8 assay was performed to determine the cell proliferation; flow cytometry was used to analyze the cell cycle profiles and apoptosis; and the protein levels of ADAR1, p53, p21, and cyclin D1 were measured by western blotting. The results showed that the cell proliferation was greatly inhibited, G1 cell cycle was arrested, and apoptosis was induced after 8-Cl-Ado exposure. ADAR1 and cyclin D1 protein levels were dramatically decreased, while p53 and p21 levels were increased after 8-Cl-Ado exposure. Moreover, the cell growth inhibition was rescued, apoptosis was reduced, and p53 and p21 protein levels were downregulated, while cyclin D1 was upregulated when cells were transfected with plasmids expressing ADAR1 proteins. More importantly, RNA-binding domain of ADAR1 is critical to the cell growth inhibition of breast cancer cells exposed to 8-Cl-Ado. Together, 8-Cl-Ado inhibits the cell proliferation, induces G1 phase arrest and apoptosis at least by targeting ADAR1/p53/p21 signaling pathway. The findings may provide us with insights into the role of ADAR1 in breast cancer progression and help us better understand the effects of 8-Cl-Ado in the treatment of breast cancer.
    Subject(s): 8-Cl-Ado ; ADAR1 ; Adenosine ; Antitumor activity ; Apoptosis ; Autophagy ; Breast cancer ; breast cancer cells ; Cell cycle ; Cell growth ; Cell proliferation ; Cholecystokinin ; Chronic lymphatic leukemia ; Cyclin D1 ; Cyclin-dependent kinase inhibitor p21 ; D1 protein ; double-stranded RNA-binding domain ; Flow cytometry ; G1 phase ; GTP-binding protein ; Lung cancer ; Lymphatic leukemia ; Original ; p53 Protein ; Phagocytosis ; Plasmids ; Proteins ; Ribonucleic acid ; RNA ; Signal transduction ; Tumor cell lines ; Western blotting
    ISSN: 0963-6897
    E-ISSN: 1555-3892
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Source: ProQuest Central
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