In this study, the phenotype and immune response of dendritic cells exposed to hyperglycemia were characterized in vitro and in vivo using the streptozotocin (STZ)‐induced diabetes model. Expression of the costimulatory molecule CD86 was found to reliably increase when dendritic cells were exposed to hyperglycemia. Additionally, hydrogel‐based delivery of the anti‐inflammatory molecule interleukin‐10 (IL‐10) was shown to partially inhibit these effects in vivo. Abstract Dendritic cells are key...
Abstract Stem cells can differentiate to diverse cell types in our body, and they hold great promises in both basic research and clinical therapies. For specific stem cell types, distinctive nutritional and signaling components are required to maintain the proliferation capacity and differentiation potential in cell culture. Various vitamins play essential roles in stem cell culture to modulate cell survival, proliferation and differentiation. Besides their common nutritional functions,...
Cells, Vol. 8, Pages 1378: Inhibition of GSK3β Reduces Ectopic Lipid Accumulation and Induces Autophagy by the AMPK Pathway in Goat Muscle Satellite Cells Cells doi: 10.3390/cells8111378 Authors: Wang Liu Zhan Guo Yang Zhong Li Zhang Wang Ectopic lipid accumulation in muscle is important not only for obesity and myopathy treatment, but also for meat quality improvement in farm animals. However, the molecular mechanisms involved in lipid metabolism in...
Cells, Vol. 8, Pages 1377: Purine DNA Lesions at Different Oxygen Concentration in DNA Repair-Impaired Human Cells (EUE-siXPA) Cells doi: 10.3390/cells8111377 Authors: Krokidis Parlanti D’Errico Pascucci Pino Alimonti Pietraforte Masi Ferreri Chatgilialoglu Xeroderma Pigmentosum (XP) is a DNA repair disease characterized by nucleotide excision repair (NER) malfunction, leading to photosensitivity and increased incidence of skin malignancies. The role...
Cells, Vol. 8, Pages 1376: TRPC6-Mediated ERK1/2 Activation Increases Dentate Granule Cell Resistance to Status Epilepticus Via Regulating Lon Protease-1 Expression and Mitochondrial Dynamics Cells doi: 10.3390/cells8111376 Authors: Kim Park Choi Kong Kang Transient receptor potential canonical channel-6 (TRPC6) is one of the Ca2+-permeable non-selective cation channels. TRPC6 is mainly expressed in dentate granule cell (DGC), which is one of the most resistant neuronal...
Abstract CxxC-finger protein 1 (CFP1)-mediated trimethylated histone H3 at lysine-4 (H3K4me3) during oocyte development enables the oocyte genome to establish the competence to generate a new organism. Nevertheless, it remains unclear to which extent this epigenetic modification forms an instructive component of ovarian follicle development. We investigated the ovarian functions using an oocyte-specific Cxxc1 knockout mouse model, in which the H3K4me3 accumulation is downregulated...
Cells, Vol. 8, Pages 1374: Physical Activity Prevents Cartilage Degradation: A Metabolomics Study Pinpoints the Involvement of Vitamin B6 Cells doi: 10.3390/cells8111374 Authors: Deiana Malerba Dalle Carbonare Cheri Patuzzo Tsenov Moron Dalla Tor Mori Saviola Zipeto Schena Mottes Valenti Osteoarthritis (OA) is predominantly characterized by the progressive degradation of articular cartilage, the connective tissue produced by chondrocytes,...
Cells, Vol. 8, Pages 1375: Alternative Splicing of RAD6B and Not RAD6A is Selectively Increased in Melanoma: Identification and Functional Characterization Cells doi: 10.3390/cells8111375 Authors: Gajan Martin Kim Joshi Michelhaugh Sloma Mittal Firestine Shekhar Rad6B, a principal component of the translesion synthesis pathway, and activator of canonical Wnt signaling, plays an essential role in cutaneous melanoma development and progression. As Rad6...
Publication date: Available online 1 November 2019Source: Cellular SignallingAuthor(s): Antimo Cutone, Barbara Colella, Andrea Pagliaro, Luigi Rosa, Maria Stefania Lepanto, Maria Carmela Bonaccorsi di Patti, Piera Valenti, Sabrina Di Bartolomeo, Giovanni MusciAbstractGlioblastoma, the most lethal form of brain cancer, is characterized by fast growth, migration and invasion of the surrounding parenchyma, with epithelial-to-mesenchymal transition (EMT)-like process being mostly responsible for tumour...
Publication date: Available online 31 October 2019Source: Cellular SignallingAuthor(s): Lance K. Blevins, Jiajun Zhou, Robert Crawford, Norbert E. KaminskiAbstract2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant formed as a byproduct in organic synthesis and burning of organic materials. TCDD has potent immunotoxic effects in B lymphocytes resulting in decreased cellular activation and suppressed IgM secretion following activation with CD40 ligand. Previous work...
Cells, Vol. 8, Pages 1373: Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues Cells doi: 10.3390/cells8111373 Authors: Herring Elison Tessem The Nr4a family of nuclear hormone receptors is composed of three members—Nr4a1/Nur77, Nr4a2/Nurr1 and Nr4a3/Nor1. While currently defined as ligandless, these transcription factors have been shown to regulate varied processes across a host of tissues. Of particular interest,...
The most straightforward applications of proteomics database searching involve intracellular proteins. Although intracellular gene products number in the thousands, their well-defined post-translational modifications (PTMs) makes database searching practical. By contrast, cell surface and extracellular matrisome proteins pass through the secretory pathway where many become glycosylated, modulating their physicochemical properties, adhesive interactions, and diversifying their functions. Although...
Protein methylation has been implicated in many important biological contexts including signaling, metabolism, and transcriptional control. Despite the importance of this post-translational modification, the global analysis of protein methylation by mass spectrometry-based proteomics has not been extensively studied because of the lack of robust, well-characterized techniques for methyl peptide enrichment. Here, to better investigate protein methylation, we compared two methods for methyl peptide...
HLA-B*40:02 is one of a few major histocompatibility complex class I (MHC-I) molecules associated with ankylosing spondylitis (AS) independently of HLA-B*27. The endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme that process MHC-I ligands and preferentially trims N-terminal basic residues, is also a risk factor for this disease. Like HLA-B*27 and other AS-associated MHC-I molecules, HLA-B*40:02 binds a relatively high percentage of peptides with ERAP2-susceptible residues. In this study,...
Secretory Immunoglobulin A (SIgA) is central to mucosal immunity: represents one of the main immunological mechanisms of defense against the potential attack of pathogens. During lactation SIgA is produced by plasmablasts in the mammary gland and is present in breast milk, playing a vital role in the passive immunity of the newborn. Interestingly, the different components of SIgA are highly N-glycosylated, and these N-Glycans have an essential role in health maintenance. In this work, we performed...
Tamoxifen has been clinically used in treating estrogen receptor (ER)-positive breast cancer for over 30 years. The most challenging aspect associated with tamoxifen therapy is the development of resistance in initially responsive breast tumors. We applied a parallel-reaction monitoring (PRM)-based quantitative proteomic method to examine the differential expression of kinase proteins in MCF-7 and the isogenic tamoxifen-resistant (TamR) cells. We were able to quantify the relative protein expression...
Post-translational modification confers diverse functional properties to immune system proteins. The composition of serum proteins such as immunoglobulin G (IgG) strongly associates with disease including forms lacking a fucose modification of the crystallizable fragment (Fc) asparagine(N)-linked glycan that show increased effector function, however, virtually nothing is known about the composition of cell surface receptors or their bound ligands in situ because of low abundance in the circulating...
We have developed ComplexBrowser, an open source, online platform for supervised analysis of quantitative proteomic data (label free and isobaric mass tag based) that focuses on protein complexes. The software uses manually curated information from CORUM and Complex Portal databases to identify protein complex components. For the first time, we provide a Complex Fold Change (CFC) factor that identifies up- and downregulated complexes based on the level of complex subunits coregulation. The software...
The direct association of the genome, transcriptome, metabolome, lipidome and proteome with the serum glycome has revealed systems of interconnected cellular pathways. The exact roles of individual glycoproteomes in the context of disease have yet to be elucidated. In a move toward personalized medicine, it is now becoming critical to understand disease pathogenesis, and the traits, stages, phenotypes and molecular features that accompany it, as the disruption of a whole system. To this end, we have...
N-glycosylation alteration has been reported in liver diseases. Characterizing N-glycopeptides that correspond to N-glycan structure with specific site information enables better understanding of the molecular pathogenesis of liver damage and cancer. Here, unbiased quantification of N-glycopeptides of a cluster of serum glycoproteins with 40–55 kDa molecular weight (40-kDa band) was investigated in hepatitis B virus (HBV)-related liver diseases. We used an N-glycopeptide method based on 18O/16O C-terminal...
Toxoplasma gondii is a unicellular protozoan parasite of the phylum Apicomplexa. The parasite repeatedly goes through a cycle of invasion, division and induction of host cell rupture, which is an obligatory process for proliferation inside warm-blooded animals. It is known that the biology of the parasite is controlled by a variety of mechanisms ranging from genomic to epigenetic to transcriptional regulation. In this study, we investigated the global protein posttranslational lysine crotonylation...
The Golgi-specific Brefeldin-A resistance factor 1 (GBF1) is the only large GEF that regulates Arf activation at the cis-Golgi and is actively recruited to membranes on an increase in Arf-GDP. Recent studies have revealed that GBF1 recruitment requires one or more heat-labile and protease-sensitive protein factor(s) (Quilty et al., 2018, J. Cell Science, 132). Proximity-dependent biotinylation (BioID) and mass spectrometry from enriched Golgi fractions identified GBF1 proximal proteins that may regulate...
Soybean (Glycine max (L.) Merrill) is an important component of the human diet and animal feed, but soybean production is limited by abiotic stresses especially salinity. We recently found that rhizobia inoculation enhances soybean tolerance to salt stress, but the underlying mechanisms are unaddressed. Here, we used quantitative phosphoproteomic and metabonomic approaches to identify changes in phosphoproteins and metabolites in soybean roots treated with rhizobia inoculation and salt. Results revealed...
Receptors expressed on the plasma membrane and their interacting partners critically regulate cellular communication during homeostasis and disease, and as such represent main therapeutic targets. Despite its importance for drug development, receptor-ligand proteomics has remained a daunting field, in part because of the challenges associated to the study of membrane-expressed proteins. Here, to enable sensitive detection of receptor-ligand interactions in high throughput, we implement a new platform,...
Treatments are emerging for the neuronal ceroid lipofuscinoses (NCLs), a group of similar but genetically distinct lysosomal storage diseases. Clinical ratings scales measure long-term disease progression and response to treatment but clinically useful biomarkers have yet to be identified in these diseases. We have conducted proteomic analyses of brain and cerebrospinal fluid (CSF) from mouse models of the most frequently diagnosed NCL diseases: CLN1 (infantile NCL), CLN2 (classical late infantile...
Protein N termini unambiguously identify truncated, alternatively translated or modified proteoforms with distinct functions and reveal perturbations in disease. Selective enrichment of N-terminal peptides is necessary to achieve proteome-wide coverage for unbiased identification of site-specific regulatory proteolytic processing and protease substrates. However, many proteolytic processes are strictly confined in time and space and therefore can only be analyzed in minute samples that provide insufficient...
Abstract Next‐generation sequencing has enabled genetic and genomic characterization of melanoma to an unprecedent depth. However, the high mutational background plus the limited deep‐coverage whole‐genome sequencing performed on cutaneous melanoma samples, make difficult the identification of novel driver mutations. We sought to explore the somatic mutation portfolio in exonic and gene regulatory regions in human melanoma samples, for which we performed targeted sequencing of tumors and matched...
Abstract Primary central nervous system melanoma is rare and characterized by a variable prognosis, and no current treatment guidelines exist. We describe the clinical course of a 70‐year‐old female diagnosed with primary leptomeningeal melanoma (LMN) whose case represents the diagnostic and management challenges of this tumor. Targeted genomic sequencing of 315 genes from this tumor revealed GNAQ Q209L mutation and low (4 mutations/Megabase) tumor mutation burden (TMB). Wildtype NRAS, KIT, and...
Abstract Skin pigmentation involves the production of the pigment melanin by melanocytes, in melanosomes and subsequent transfer to keratinocytes. Within keratinocytes, melanin polarizes to the apical perinuclear region to form a protective cap, shielding the DNA from ultraviolet radiation‐induced damage. Previously, we found evidence to support the exocytosis by melanocytes of the melanin core, termed melanocore, followed by endo/phagocytosis by keratinocytes as a main form of transfer, with Rab11b...
In this study, we report for the first time, a novel targeted self‐assembled drug delivery system based on PEG‐PLA nanoparticles (PEG‐PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ACUPA in prostate cancer cell line Abstract Prostate cancer (PCa) is one of the most prevalent non‐drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first...
Taken together, LINC00629 competitively bound to microRNA‐196b‐5p to upregulate aquaporin 4 expression, thereby inhibiting gastric cancer progression. Therefore, understanding of this mechanism may help to improve gastric cancer treatment. Abstract Gastric cancer continues to be a common cancer in the world with high incidence and mortality. Accumulating evidence has implicated long noncoding RNAs (lncRNAs) in gastric cancer progression. Here, this study identified the potential role of a novel...
MiR‐142‐3p is downregulated in breast cancer (BC) tissues and cell lines. MiR‐142‐3p may act as a tumor suppressor by regulating cell proliferation, migration, invasion, angiogenesis, and epithelial‐to‐mesenchymal transition process through directly downregulation of ras‐related C3 botulinum toxin substrate 1 expression and subsequently inhibiting the activity of PAK1 phosphorylation in BC. Abstract MicroRNA‐142‐3p (miR‐142‐3p) was previously investigated in various cancers, whereas, it's role...
miR‐488 attenuates lipopolysaccharides (LPS)‐induced BEND cell inflammatory response by inhibiting translation of Rac family small GTPase 1 (Rac1) and reducing reactive oxygen species (ROS) accumulation in cells. Our results support the fact that the inflammatory response nature of BEND cells stimulated by LPS stimulates the intracellular accumulation of ROS and the activation of the AKT/NF‐κB signaling pathway by miR‐488 directly targeting the negative phase of Rac1. Abstract Endometritis...
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