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Luigi Mario Castello, Marco Baldrighi, Luca Molinari, Livia Salmi, Vincenzo Cantaluppi, Rosanna Vaschetto, Greta Zunino, Marco Quaglia, Mattia Bellan, Francesco Gavelli, Paolo Navalesi, Gian Carlo Avanzi, Annalisa Chiocchetti
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host-response to infections. Osteopontin (OPN) is an extracellular matrix protein involved in the inflammatory response. Our aim was to evaluate the diagnostic and prognostic performance in sepsis of a single OPN determination in the Emergency Department (ED). We conducted a single-centre prospective observational study in an Italian ED where we enrolled 102 consecutive patients presenting with suspected infection and qSOFA ≥ 2. OPN plasma concentration was found to be an independent predictor of sepsis (OR = 1...
February 18, 2019: Cells
Mohamed H Abumaree, Seham Al Harthy, Abdullah M Al Subayyil, Manal A Alshabibi, Fawaz M Abomaray, Tanvier Khatlani, Bill Kalionis, Mohammed F El-Muzaini, Mohammed A Al Jumah, Dunia Jawdat, Abdullah O Alawad, Ahmed S AlAskar
Placental mesenchymal stem cells from maternal decidua basalis tissue (DBMSCs) are promising cells for tissue repair because of their multilineage differentiation and ability to protect endothelial cells from injury. Here, we examined DBMSC interaction with macrophages and whether this interaction could modulate the characteristics and functions of these macrophages. We induced monocytes to differentiate into M1-like macrophages in the presence of DBMSCs. DBMSC effects on differentiation were evaluated using microscopy, flow cytometry, and ELISA...
February 18, 2019: Cells
Dominik C Fuhrmann, Catherine Olesch, Nina Kurrle, Frank Schnütgen, Sven Zukunft, Ingrid Fleming, Bernhard Brüne
Hypoxia poses a stress to cells and decreases mitochondrial respiration, in part by electron transport chain (ETC) complex reorganization. While metabolism under acute hypoxia is well characterized, alterations under chronic hypoxia largely remain unexplored. We followed oxygen consumption rates in THP-1 monocytes during acute (16 h) and chronic (72 h) hypoxia, compared to normoxia, to analyze the electron flows associated with glycolysis, glutamine, and fatty acid oxidation. Oxygen consumption under acute hypoxia predominantly demanded pyruvate, while under chronic hypoxia, fatty acid- and glutamine-oxidation dominated...
February 18, 2019: Cells
Oula El Atat, Amira Fakih, Mirvat El-Sibai
Angiogenesis is a hallmark of cancer cell malignancy. The role of the RHO family GTPase RHOG in angiogenesis in vascular endothelial cells has recently been elucidated. However, the regulation of RHOG during this process, as well as its cross-talk with other RHO GTPases, have yet to be fully examined. In this study, we found that siRNA-mediated depletion of RHOG strongly inhibits tube formation in vascular endothelial cells (ECV cells), an effect reversed by transfecting dominant active constructs of CDC42 or RAC1 in the RHOG-depleted cells...
February 18, 2019: Cells
Greggory S Laberge, Eric Duvall, Kay Haedicke, John Pawelek
According to estimates from the International Agency for Research on Cancer, by the year 2030 there will be 22 million new cancer cases and 13 million deaths per year. The main cause of cancer mortality is not the primary tumor itself but metastasis to distant organs and tissues, yet the mechanisms of this process remain poorly understood. Leukocyte⁻cancer cell fusion and hybrid formation as an initiator of metastasis was proposed more than a century ago by the German pathologist Prof. Otto Aichel. This proposal has since been confirmed in more than 50 animal models and more recently in one patient with renal cell carcinoma and two patients with malignant melanoma...
February 18, 2019: Cells
Parisa Tajer, Karin Pike-Overzet, Sagrario Arias, Menzo Havenga, Frank J T Staal
Expansion of hematopoietic stem cells (HSCs) for therapeutic purposes has been a "holy grail" in the field for many years. Ex vivo expansion of HSCs can help to overcome material shortage for transplantation purposes and genetic modification protocols. In this review, we summarize improved understanding in blood development, the effect of niche and conservative signaling pathways on HSCs in mice and humans, and also advances in ex vivo culturing protocols of human HSCs with cytokines or small molecule compounds...
February 18, 2019: Cells
Yujing Han, Jing Feng, Linjian Xia, Xin Dong, Xinyang Zhang, Shihan Zhang, Yuqi Miao, Qidi Xu, Shan Xiao, Zhixiang Zuo, Laixin Xia, Chunjiang He
N6-methyladenosine (m⁶A) has been identified in various biological processes and plays important regulatory functions in diverse cells. However, there is still no visualization database for exploring global m⁶A patterns across cell lines. Here we collected all available MeRIP-Seq and m⁶A-CLIP-Seq datasets from public databases and identified 340,950 and 179,201 m⁶A peaks dependent on 23 human and eight mouse cell lines respectively. Those m⁶A peaks were further classified into mRNA and lncRNA groups...
February 17, 2019: Cells
Danton H O'Day
The nucleoli of Dictyostelium discoideum have a comparatively unique, non-canonical, localization adjacent to the inner nuclear membrane. The verified nucleolar proteins of this eukaryotic microbe are detailed while other potential proteins are introduced. Heat shock protein 32 (Hsp32), eukaryotic translation initiation factor 6 (eIF6), and tumour necrosis factor receptor-associated protein 1 (TRAP1) are essential for cell survival. NumA1, a breast cancer type 1 susceptibility protein-C Terminus domain-containing protein linked to cell cycle, functions in the regulation of nuclear number...
February 17, 2019: Cells
Gloria Bellin, Chiara Gardin, Letizia Ferroni, Juan Carlos Chachques, Massimo Rogante, Dinko Mitrečić, Roberto Ferrari, Barbara Zavan
Exosomes are a subgroup of extracellular vesicles containing a huge number of bioactive molecules. They represent an important means of cell communication, mostly between different cell populations, with the purpose of maintaining tissue homeostasis and coordinating the adaptive response to stress. This type of intercellular communication is important in the cardiovascular field, mainly due to the fact that the heart is a complex multicellular system. Given the growing interest in the role of exosomes in cardiovascular diseases and the numerous studies published in the last few decades, we focused on the most relevant results about exosomes in the cardiovascular filed starting from their characterization, passing through the study of their function, and ending with perspectives for their use in cardiovascular therapies...
February 17, 2019: Cells
Lucile M-P Jeusset, Kirk J McManus
Histone ubiquitination is a critical epigenetic mechanism regulating DNA-driven processes such as gene transcription and DNA damage repair. Importantly, the cellular machinery regulating histone ubiquitination is frequently altered in cancers. Moreover, aberrant histone ubiquitination can drive oncogenesis by altering the expression of tumor suppressors and oncogenes, misregulating cellular differentiation and promoting cancer cell proliferation. Thus, targeting aberrant histone ubiquitination may be a viable strategy to reprogram transcription in cancer cells, in order to halt cellular proliferation and induce cell death, which is the basis for the ongoing development of therapies targeting histone ubiquitination...
February 16, 2019: Cells
Kunio Shinohara, Shigenobu Toné, Takeo Ejima, Takuji Ohigashi, Atsushi Ito
Soft X-ray microscopy was applied to study the quantitative distribution of DNA, RNA, histone, and proteins other than histone (represented by BSA) in mammalian cells, apoptotic nuclei, and a chromosome at spatial resolutions of 100 to 400 nm. The relative distribution of closely related molecules, such as DNA and RNA, was discriminated by the singular value decomposition (SVD) method using aXis2000 software. Quantities of nucleic acids and proteins were evaluated using characteristic absorption properties due to the 1s⁻π * transition of N=C in nucleic acids and amide in proteins, respectively, in the absorption spectra at the nitrogen K absorption edge...
February 16, 2019: Cells
Kara Turner, Colleen Lynch, Hannah Rouse, Vimal Vasu, Darren K Griffin
Reproductive ageing in women, particularly after the age of 35, is associated with an exponential increase in the proportion of chromosomally abnormal oocytes produced. Several hypotheses have attempted to explain this observation, including the 'limited oocyte pool' hypothesis and the 'two-hit' hypothesis, the latter explaining that a depletion in oocyte quality with age results from the multiple opportune stages for errors to occur in meiosis. Recently however, the telomere theory of reproductive ageing in women has been proposed...
February 16, 2019: Cells
Marianne Grafe, Petros Batsios, Irene Meyer, Daria Lisin, Otto Baumann, Martin W Goldberg, Ralph Gräf
Nuclear lamins are nucleus-specific intermediate filaments (IF) found at the inner nuclear membrane (INM) of the nuclear envelope (NE). Together with nuclear envelope transmembrane proteins, they form the nuclear lamina and are crucial for gene regulation and mechanical robustness of the nucleus and the whole cell. Recently, we characterized Dictyostelium NE81 as an evolutionarily conserved lamin-like protein, both on the sequence and functional level. Here, we show on the structural level that the Dictyostelium NE81 is also capable of assembling into filaments, just as metazoan lamin filament assemblies...
February 16, 2019: Cells
Valeria Cordone, Alessandra Pecorelli, Mascia Benedusi, Silvano Santini, Stefano Falone, Joussef Hayek, Fernanda Amicarelli, Giuseppe Valacchi
Rett syndrome (RTT) is a human neurodevelopmental disorder, whose pathogenesis has been linked to both oxidative stress and subclinical inflammatory status (OxInflammation). Methylglyoxal (MG), a glycolytic by-product with cytotoxic and pro-oxidant power, is the major precursor in vivo of advanced glycation end products (AGEs), which are known to exert their detrimental effect via receptor- (e.g., RAGE) or non-receptor-mediated mechanisms in several neurological diseases. On this basis, we aimed to compare fibroblasts from healthy subjects (CTR) with fibroblasts from RTT patients (N = 6 per group), by evaluating gene/protein expression patterns, and enzymatic activities of glyoxalases (GLOs), along with the levels of MG-dependent damage in both basal and MG-challenged conditions...
February 15, 2019: Cells
Helena Soares, Bruno Carmona, Sofia Nolasco, Luís Viseu Melo, João Gonçalves
Eukaryotic cilia are microtubule-based organelles that protrude from the cell surface to fulfill sensory and motility functions. Their basic structure consists of an axoneme templated by a centriole/basal body. Striking differences in ciliary ultra-structures can be found at the ciliary base, the axoneme and the tip, not only throughout the eukaryotic tree of life, but within a single organism. Defects in cilia biogenesis and function are at the origin of human ciliopathies. This structural/functional diversity and its relationship with the etiology of these diseases is poorly understood...
February 14, 2019: Cells
Weijie Cao, Xingang Li, Xiaoyu Zhang, Jie Zhang, Qi Sun, Xizhu Xu, Ming Sun, Qiuyue Tian, Qihuan Li, Hao Wang, Jiaonan Liu, Xiaoni Meng, Lijuan Wu, Manshu Song, Haifeng Hou, Youxin Wang, Wei Wang
BACKGROUND: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. METHODS: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent...
February 14, 2019: Cells
Gabriela Berg, Magalí Barchuk, Verónica Miksztowicz
Extracellular matrix (ECM) remodeling is required for many physiological and pathological processes. Metalloproteinases (MMPs) are endopeptidases which are able to degrade different components of the ECM and nucleus matrix and to cleave numerous non-ECM proteins. Among pathological processes, MMPs are involved in adipose tissue expansion, liver fibrosis, and atherosclerotic plaque development and vulnerability. The expression and the activity of these enzymes are regulated by different hormones and growth factors, such as insulin, leptin, and adiponectin...
February 14, 2019: Cells
Emi Hattori, Rieko Oyama, Tadashi Kondo
Sarcomas are rare mesenchymal malignant tumors with unique biological and clinical features. Given their diversity, heterogeneity, complexity, and rarity, the clinical management of sarcomas is quite challenging. Cell lines have been used as indispensable tools for both basic research and pre-clinical studies. However, empirically, sarcoma cell lines are not readily available. To understand the present status of sarcoma cell lines and identify their current challenges, we systematically reviewed reports on sarcoma cell lines...
February 13, 2019: Cells
Syed Farhan Ahmad, Cesar Martins
Supernumerary B chromosomes (Bs) are extra karyotype units in addition to A chromosomes, and are found in some fungi and thousands of animals and plant species. Bs are uniquely characterized due to their non-Mendelian inheritance, and represent one of the best examples of genomic conflict. Over the last decades, their genetic composition, function and evolution have remained an unresolved query, although a few successful attempts have been made to address these phenomena. A classical concept based on cytogenetics and genetics is that Bs are selfish and abundant with DNA repeats and transposons, and in most cases, they do not carry any function...
February 13, 2019: Cells
Ben Wielockx, Tatyana Grinenko, Peter Mirtschink, Triantafyllos Chavakis
The regulation of oxygen (O₂) levels is crucial in embryogenesis and adult life, as O₂ controls a multitude of key cellular functions. Low oxygen levels (hypoxia) are relevant for tissue physiology as they are integral to adequate metabolism regulation and cell fate. Hence, the hypoxia response is of utmost importance for cell, organ and organism function and is dependent on the hypoxia-inducible factor (HIF) pathway. HIF pathway activity is strictly regulated by the family of oxygen-sensitive HIF prolyl hydroxylase domain (PHD) proteins...
February 13, 2019: Cells
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