bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Memory for Relationship Actions by Transcranial Direct Current Stimulation of the Superior Temporal Sulcus
Authors: Marrero Hipólito , Yagual Sara Nila , García-Marco Enrique , Gámez Elena , Beltrán David , Díaz Jose Miguel , Urrutia Mabel
Published: July 2020

We examine the effect of transcranial direct current stimulation (tDCS) of right superior temporal sulcus (rSTS) in memorization of approach/avoidance relationship-action sentences; for example, “Alejandro accepted/rejected Marta in his group.” Sixty-five university students participated in a tDCS study, in which a between-subjects design was adopted. Sixty-four participants were also given the behavioral approach system (BAS) and behavioral inhibition system (BIS) scales. Participants were subjected to 20 min of stimulation: anodal (N = 24), cathodal (N = 21), or sham (N = 20); subsequently, they were given a list of 40 sentences (half approach and half avoidance) and told to try to memorize them. Finally, they performed a changed/same memory task (half the sentences were the “same” and half were “changed”). Previously, we had examined performance in the memory task without tDCS with another group of participants (N = 20). We found that anodal stimulation improved d’ index of discriminability (hits-false alarms) compared to sham and cathodal conditions for both approach and avoidance sentences. Moreover, the comparison between anodal and task-alone performance showed that stimulation improved d’ index of approach sentences more, as task-alone performance showed better discrimination for avoidance than for approach. Likewise, we explored a potential modulation of tDCS effect by (BAS) and (BIS) traits. We found that d’ index improvement in anodal stimulation condition only benefited low BAS and low BIS participants. Implications of these results are discussed in the context of rSTS function in encoding and memorizing verbally described intentional relationship-actions and the role of individual differences on modulating tDCS effect.
Knockdown of Leptin Receptor Affects Macrophage Phenotype in the Tumor Microenvironment Inhibiting Breast Cancer Growth and Progression
Authors: Gelsomino Luca , Naimo Giuseppina Daniela , Malivindi Rocco , Augimeri Giuseppina , Panza Salvatore , Giordano Cinzia , Barone Ines , Bonofiglio Daniela , Mauro Loredana , Catalano Stefania , Andò Sebastiano
Published: July 2020

Aberrant leptin (Ob) signaling, a hallmark of obesity, has been recognized to influence breast cancer (BC) biology within the tumor microenvironment (TME). Here, we evaluated the impact of leptin receptor (ObR) knockdown in affecting BC phenotype and in mediating the interaction between tumor cells and macrophages, the most abundant immune cells within the TME. The stable knockdown of ObR (ObR sh) in ERα-positive and ERα-negative BC cells turned the tumor phenotype into a less aggressive one, as evidenced by in vitro and in vivo models. In xenograft tumors and in co-culture experiments between circulating monocytes and BC cells, the absence of ObR reduced the recruitment of macrophages, and also affected their cytokine mRNA expression profile. This was associated with a decreased expression and secretion of monocyte chemoattractant protein-1 in ObR sh clones. The loss of Ob/ObR signaling modulated the immunosuppressive TME, as shown by a reduced expression of programmed death ligand 1/programmed cell death protein 1/arginase 1. In addition, we observed increased phagocytic activity of macrophages compared to control Sh clones in the presence of ObR sh-derived conditioned medium. Our findings, addressing an innovative role of ObR in modulating immune TME, may open new avenues to improve BC patient health care.
Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
Authors: Midha Mohit K. , Huang Yu-Feng , Yang Hsiao-Hsiang , Fan Tan-Chi , Chang Nai-Chuan , Chen Tzu-Han , Wang Yu-Tai , Kuo Wen-Hung , Chang King-Jen , Shen Chen-Yang , Yu Alice L. , Chiu Kuo-Ping , Chen Chien-Jen
Published: July 2020

Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)–tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include TP53 (40% prevalence), PIK3CA (37%), GATA3 (17%) and KMT2C (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes MUC17 (19%), FLG (16%) and NEBL (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, MUC16 (19%) and KRT18 (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age.
Mapping and Quantification of Non-Coding RNA Originating from the rDNA in Human Glioma Cells
Authors: Sadova Anastasia A. , Kupriyanova Natalia S. , Pavlova Galina V.
Published: July 2020

Ribosomal DNA is one of the most conserved parts of the genome, especially in its rRNA coding regions, but some puzzling pieces of its noncoding repetitive sequences harbor secrets of cell growth and development machinery. Disruptions in the neat mechanisms of rDNA orchestrating the cell functioning result in malignant conversion. In cancer cells, the organization of rRNA coding genes and their transcription somehow differ from that of normal cells, but little is known about the particular mechanism for this switch. In this study, we demonstrate that the region ~2 kb upstream of the rDNA promoter is transcriptionally active in one type of the most malignant human brain tumors, and we compare its expression rate to that of healthy human tissues and cell cultures. Sense and antisense non-coding RNA transcripts were detected and mapped, but their secondary structure and functions remain to be elucidated. We propose that the transcripts may relate to a new class of so-called promoter-associated RNAs (pRNAs), or have some other regulatory functions. We also hope that the expression of these non-coding RNAs can be used as a marker in glioma diagnostics and prognosis.
Head and Neck Cancer Metastasis and the Effect of the Local Soluble Factors, from the Microenvironment, on Signalling Pathways: Is It All about the Akt?
Authors: Ahmed Hanan , Ghoshal Arpa , Jones Sarah , Ellis Ian , Islam Mohammad
Published: July 2020

The signalling pathways involved in metastasis of oral adenoid cancer cells (TYS) in response to cancer-associated fibroblasts (COM D24) and normal oral mucosal fibroblasts (MM1) was examined. Metastatic cell behaviour was observed by cell-scatter, 3-D-collagen gel migration, and 3-D-spheroid invasion assays. Akt (v-Akt murine thymoma viral oncogene), MAPK(Mitogen activated protein kinase), EGFR (Epidermal growth factor receptor), TGFβRI (Transforming growth factor beta receptor 1), and CXCR4 (C-X-C chemokine receptor 4) inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western blotting. COM-CM (conditioned medium from COM D24 cells) and MM1-CM (conditioned medium from MM1 cells) stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM-induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into collagen gels from the spheroids was stimulated by CM from both fibroblast cell lines, compared to the negative control. COM cells stimulated TYS invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive the addition of an EGFR inhibitor. This suggests that CAFs stimulate head and neck cancer cell migration and invasion in an Akt- dependent manner. Akt may represent a potential target for inhibitor design to treat metastatic head and neck cancer.
Controlling TIME: How MNK Kinases Function to Shape Tumor Immunity
Authors: Pham Thao N.D. , Spaulding Christina , Munshi Hidayatullah G.
Published: July 2020

A number of studies have clearly established the oncogenic role for MAPK-interacting protein kinases (MNK) in human malignancies. Modulation of MNK activity affects translation of mRNAs involved in cancer development, progression, and resistance to therapies. As a result, there are ongoing efforts to develop and evaluate MNK inhibitors for cancer treatment. However, it is important to recognize that MNK activity also plays an important role in regulating the innate and adaptive immune systems. A better understanding of the role of MNK kinases and MNK-mediated signals in regulating the immune system could help mitigate undesired side effects while maximizing therapeutic efficacy of MNK inhibitors. Here, we provide a systematic review on the function of MNK kinases and their substrates in immune cells.
Oxidative Stress and Apoptotic Responses Elicited by Nostoc-Synthesized Silver Nanoparticles against Different Cancer Cell Lines
Authors: Hamida Reham Samir , Albasher Gadah , Bin-Meferij Mashael Mohammed
Published: July 2020

Green nanoparticles represent a revolution in bionanotechnology, providing opportunities to fight life-threatening diseases, such as cancer, with less risk to the environment and to human health. Here, for the first time, we systematically investigated the anticancer activity and possible mechanism of novel silver nanoparticles (N-SNPs) synthesized by Nostoc Bahar M against the MCF-7 breast cancer cells, HCT-116 colorectal adenocarcinoma cells, and HepG2 liver cancer cells, using cell viability assays, morphological characterization with inverted light and transmission electron microscopy, antioxidants and enzymes (glutathione peroxidase (GPx), glutathione (GSH), adenosine triphosphatase (ATPase), and lactate dehydrogenase (LDH)), and western blotting (protein kinase B (Akt), phosphorylated-Akt (p-Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma 2 (Bcl-2), tumor suppressor (p53), and caspase 3). N-SNPs decreased the viability of MCF-7, HCT-116, and HepG2 cells, with half-maximal inhibitory concentrations of 54, 56, and 80 µg/mL, respectively. They also significantly increased LDH leakage, enhanced oxidative stress via effects on antioxidative markers, and caused metabolic stress by significantly decreasing ATPase levels. N-SNPs caused extensive ultrastructural alterations in cell and nuclear structures, as well as in various organelles. Furthermore, N-SNPs triggered apoptosis via the activation of caspase 3 and p53, and suppressed the mTOR signaling pathway via downregulating apoptosis-evading proteins in MCF-7, HCT-116, and HepG2 cells. Ultrastructural analysis, together with biochemical and molecular analyses, revealed that N-SNPs enhanced apoptosis via the induction of oxidative stress and/or through direct interactions with cellular structures in all tested cells. The cytotoxicity of Nostoc-mediated SNPs represents a new strategy for cancer treatment via targeting various cell death pathways. However, the potential of N-SNPs to be usable and biocompatible anticancer drug will depend on their toxicity against normal cells.
Clonal Hematopoiesis and Mutations of Myeloproliferative Neoplasms
Authors: Kjær Lasse
Published: July 2020

Myeloproliferative neoplasms (MPNs) are associated with the fewest number of mutations among known cancers. The mutations propelling these malignancies are phenotypic drivers providing an important implement for diagnosis, treatment response monitoring, and gaining insight into the disease biology. The phenotypic drivers of Philadelphia chromosome negative MPN include mutations in JAK2, CALR, and MPL. The most prevalent driver mutation JAK2V617F can cause disease entities such as essential thrombocythemia (ET) and polycythemia vera (PV). The divergent development is considered to be influenced by the acquisition order of the phenotypic driver mutation relative to other MPN-related mutations such as TET2 and DNMT3A. Advances in molecular biology revealed emergence of clonal hematopoiesis (CH) to be inevitable with aging and associated with risk factors beyond the development of blood cancers. In addition to its well-established role in thrombosis, the JAK2V617F mutation is particularly connected to the risk of developing cardiovascular disease (CVD), a pertinent issue, as deep molecular screening has revealed the prevalence of the mutation to be much higher in the background population than previously anticipated. Recent findings suggest a profound under-diagnosis of MPNs, and considering the impact of CVD on society, this calls for early detection of phenotypic driver mutations and clinical intervention.
Development of an Individualized Prediction Calculator for the Benefit of Postoperative Radiotherapy in Patients with Surgically Resected De Novo Stage IV Breast Cancer
Authors: Kim Byoung Hyuck , Kim Suzy , Kim Young Il , Chang Ji Hyun , Hwang Ki-Tae , Kim Sup , Cho Moon-June , Kwon Jeanny
Published: July 2020

Purpose: Locoregional treatment has been increasingly adopted for metastatic breast cancer at presentation. This study aims to develop an individualized calculator to predict the benefit of postoperative radiotherapy (PORT) for patients with surgically resected de novo stage IV breast cancer. Methods and Materials: We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with stage IV breast cancer between 2010 and 2014. After applying exclusion criteria, a total of 4473 patients were included in the analysis. Propensity score matching was used to balance the individual characteristics of the patients. After identifying the significant prognosticators, a nomogram was developed using multivariate regression models and internally validated. A web-based calculator was then constructed using a fitted survival prediction model. Results: With a median follow-up of 34 months, the three-year overall survival (OS) rates were 54.1% in the surgery alone group and 63.5% in the surgery + PORT group (p < 0.001). The survival benefit of PORT was maintained after propensity score matching (p < 0.001). Interaction testing of the prognostic variables found significant interactions between PORT and the presence of brain metastasis (p = 0.001), and between PORT and hormonal receptor expression (p = 0.018). After reviewing the performance of various models, a log-normal distributed survival model was adopted, with a C-index of 0.695. A calibration plot verified that the predicted survival rates were strongly correlated with the actual OS rates. A web-based survival calculator was constructed to provide individualized estimates of survival according to PORT. Conclusion: PORT significantly improved OS rates, though the individual benefit was affected by a number of factors. We successfully developed a nomogram and web-based calculator that predicted the prognosis according to PORT in patients with surgically resected de novo stage IV breast cancer. These tools are expected to be useful in clinical practice and in the design of related trials.
From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers—A Multidisciplinary Perspective
Authors: Accordino Giulia , Lettieri Sara , Bortolotto Chandra , Benvenuti Silvia , Gallotti Anna , Gattoni Elisabetta , Agustoni Francesco , Pozzi Emma , Rinaldi Pietro , Primiceri Cristiano , Morbini Patrizia , Lancia Andrea , Stella Giulia Maria
Published: July 2020

Despite the progress during the last decade, patients with advanced gastric and esophageal cancers still have poor prognosis. Finding optimal therapeutic strategies represents an unmet need in this field. Several prognostic and predictive factors have been evaluated and may guide clinicians in choosing a tailored treatment. Data from large studies investigating the role of immunotherapy in gastrointestinal cancers are promising but further investigations are necessary to better select those patients who can mostly benefit from these novel therapies. This review will focus on the treatment of metastatic esophageal and gastric cancer. We will review the standard of care and the role of novel therapies such as immunotherapies and CAR-T. Moreover, we will focus on the analysis of potential predictive biomarkers such as Modify as: Microsatellite Instability (MSI) and PD-L1, which may lead to treatment personalization and improved treatment outcomes. A multidisciplinary point of view is mandatory to generate an integrated approach to properly exploit these novel antiproliferative agents.
Personal Medicine and Bone Metastases: Biomarkers, Micro-RNAs and Bone Metastases
Authors: Wood Steven L. , Brown Janet E.
Published: July 2020

Bone metastasis is a major cause of morbidity within solid tumours of the breast, prostate, lung and kidney. Metastasis to the skeleton is associated with a wide range of complications including bone fractures, spinal cord compression, hypercalcaemia and increased bone pain. Improved treatments for bone metastasis, such as the use of anti-bone resorptive bisphosphonate agents, within post-menopausal women have improved disease-free survival; however, these treatments are not without side effects. There is thus a need for biomarkers, which will predict the risk of developing the spread to bone within these cancers. The application of molecular profiling techniques, together with animal model systems and engineered cell-lines has enabled the identification of a series of potential bone-metastasis biomarker molecules predictive of bone metastasis risk. Some of these biomarker candidates have been validated within patient-derived samples providing a step towards clinical utility. Recent developments in multiplex biomarker quantification now enable the simultaneous measurement of up to 96 micro-RNA/protein molecules in a spatially defined manner with single-cell resolution, thus enabling the characterisation of the key molecules active at the sites of pre-metastatic niche formation as well as tumour-stroma signalling. These technologies have considerable potential to inform biomarker discovery. Additionally, a potential future extension of these discoveries could also be the identification of novel drug targets within cancer spread to bone. This chapter summarises recent findings in biomarker discovery within the key bone metastatic cancers (breast, prostate, lung and renal cell carcinoma). Tissue-based and circulating blood-based biomarkers are discussed from the fields of genomics, epigenetic regulation (micro-RNAs) and protein/cell-signalling together with a discussion of the potential future development of these markers towards clinical development.
Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice
Authors: Schneider Simon , Shakeri Farhad , Trötschel Christian , Arévalo Lena , Kruse Alexander , Buness Andreas , Poetsch Ansgar , Steger Klaus , Schorle Hubert
Published: July 2020

Protamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studies. Apart from impaired DNA integrity, protamine-deficient human and murine sperm show multiple secondary effects, including decreased motility and aberrant head morphology. In this study, we use a Protamine-2 (Prm2)-deficient mouse model in combination with label-free quantitative proteomics to decipher the underlying molecular processes of these effects. We show that loss of the sperm’s antioxidant capacity, indicated by downregulation of key proteins like Superoxide dismutase type 1 (SOD1) and Peroxiredoxin 5 (PRDX5), ultimately initiates an oxidative stress-mediated destruction cascade during epididymal sperm maturation. This is confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for oxidative stress-mediated DNA damage. Prm2-deficient testicular sperm are not affected and initiate the proper development of blastocyst stage preimplantation embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our results provide new insight into the role of Prm2 and its downstream molecular effects on sperm function and present an important contribution to the investigation of new treatment regimens for infertile men with impaired protamination.
miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain
Authors: Sereno Marta , Videira Mafalda , Wilhelm Imola , Krizbai István A. , Brito Maria Alexandra
Published: July 2020

MicroRNAs (miRNAs) are small non-coding RNAs that mainly act by binding to target genes to regulate their expression. Due to the multitude of genes regulated by miRNAs they have been subject of extensive research in the past few years. This state-of-the-art review summarizes the current knowledge about miRNAs and illustrates their role as powerful regulators of physiological processes. Moreover, it highlights their aberrant expression in disease, including specific cancer types and the differential hosting-metastases preferences that influence several steps of tumorigenesis. Considering the incidence of breast cancer and that the metastatic disease is presently the major cause of death in women, emphasis is put in the role of miRNAs in breast cancer and in the regulation of the different steps of the metastatic cascade. Furthermore, we depict their involvement in the cascade of events underlying breast cancer brain metastasis formation and development. Collectively, this review shall contribute to a better understanding of the uniqueness of the biologic roles of miRNAs in these processes, to the awareness of miRNAs as new and reliable biomarkers and/or of therapeutic targets, which can change the landscape of a poor prognosis and low survival rates condition of advanced breast cancer patients.
The Emerging Role of Galectins and O-GlcNAc Homeostasis in Processes of Cellular Differentiation
Authors: Tazhitdinova Rada , Timoshenko Alexander V.
Published: July 2020

Galectins are a family of soluble β-galactoside-binding proteins with diverse glycan-dependent and glycan-independent functions outside and inside the cell. Human cells express twelve out of sixteen recognized mammalian galectin genes and their expression profiles are very different between cell types and tissues. In this review, we summarize the current knowledge on the changes in the expression of individual galectins at mRNA and protein levels in different types of differentiating cells and the effects of recombinant galectins on cellular differentiation. A new model of galectin regulation is proposed considering the change in O-GlcNAc homeostasis between progenitor/stem cells and mature differentiated cells. The recognition of galectins as regulatory factors controlling cell differentiation and self-renewal is essential for developmental and cancer biology to develop innovative strategies for prevention and targeted treatment of proliferative diseases, tissue regeneration, and stem-cell therapy.
Comment on: “Mitochondrial Mechanisms of Neuromuscular Junction Degeneration with Aging. Cells 2020, 9, 197”
Authors: Herbst Allen , Aiken Judd M. , McKenzie Debbie , Wanagat Jonathan
Published: July 2020

“The main conclusions are that the ageing atrophy begins as early as around 25 years of age and thereafter accelerates and, for this muscle, is caused mainly by a loss of fibers and to a lesser extent by a reduction in fiber size [...]
Feasibility of Mechanical Extrusion to Coat Nanoparticles with Extracellular Vesicle Membranes
Authors: Van Deun Jan , Roux Quentin , Deville Sarah , Van Acker Thibaut , Rappu Pekka , Miinalainen Ilkka , Heino Jyrki , Vanhaecke Frank , De Geest Bruno G. , De Wever Olivier , Hendrix An
Published: July 2020

Biomimetic functionalization to confer stealth and targeting properties to nanoparticles is a field of intense study. Extracellular vesicles (EV), sub-micron delivery vehicles for intercellular communication, have unique characteristics for drug delivery. We investigated the top-down functionalization of gold nanoparticles with extracellular vesicle membranes, including both lipids and associated membrane proteins, through mechanical extrusion. EV surface-exposed membrane proteins were confirmed to help avoid unwanted elimination by macrophages, while improving autologous uptake. EV membrane morphology, protein composition and orientation were found to be unaffected by mechanical extrusion. We implemented complementary EV characterization methods, including transmission- and immune-electron microscopy, and nanoparticle tracking analysis, to verify membrane coating, size and zeta potential of the EV membrane-cloaked nanoparticles. While successful EV membrane coating of the gold nanoparticles resulted in lower macrophage uptake, low yield was found to be a significant downside of the extrusion approach. Our data incentivize more research to leverage EV membrane biomimicking as a unique drug delivery approach in the near future.
Growth Factors, and Cytokines; Understanding the Role of Tyrosine Phosphatase SHP2 in Gametogenesis and Early Embryo Development
Authors: Idrees Muhammad , Oh Seon-Hwa , Muhammad Tahir , El-Sheikh Marwa , Song Seok-Hwan , Lee Kyeong-Lim , Kong Il-Keun
Published: July 2020

Growth factors and cytokines have vital roles in germ cell development, gamete maturation, and early embryo development. Cell surface receptors are present for growth factors and cytokines to integrate with and trigger protein signaling in the germ and embryo intracellular milieu. Src-homology-2-containing phosphotyrosine phosphatase (SHP2) is a ubiquitously expressed, multifunctional protein that plays a central role in the signaling pathways involved in growth factor receptors, cytokine receptors, integrins, and G protein-coupled receptors. Over recent decades, researchers have recapitulated the protein signaling networks that influence gamete progenitor specification as well as gamete differentiation and maturation. SHP2 plays an indispensable role in cellular growth, survival, proliferation, differentiation, and migration, as well as the basic events in gametogenesis and early embryo development. SHP2, a classic cytosolic protein and a key regulator of signal transduction, displays unconventional nuclear expression in the genital organs. Several observations provided shreds of evidence that this behavior is essential for fertility. The growth factor and cytokine-dependent roles of SHP2 and its nuclear/cytoplasmic presence during gamete maturation, early embryonic development and embryo implantation are fascinating and complex subjects. This review is intended to summarize the previous and recent knowledge about the SHP2 functions in gametogenesis and early embryo development.
MIP-1α Expression Induced by Co-Stimulation of Human Monocytic Cells with Palmitate and TNF-α Involves the TLR4-IRF3 Pathway and Is Amplified by Oxidative Stress
Authors: Sindhu Sardar , Akhter Nadeem , Wilson Ajit , Thomas Reeby , Arefanian Hossein , Al Madhoun Ashraf , Al-Mulla Fahd , Ahmad Rasheed
Published: July 2020

Metabolic inflammation is associated with increased expression of saturated free fatty acids, proinflammatory cytokines, chemokines, and adipose oxidative stress. Macrophage inflammatory protein (MIP)-1α recruits the inflammatory cells such as monocytes, macrophages, and neutrophils in the adipose tissue; however, the mechanisms promoting the MIP-1α expression remain unclear. We hypothesized that MIP-1α co-induced by palmitate and tumor necrosis factor (TNF)-α in monocytic cells/macrophages could be further enhanced in the presence of reactive oxygen species (ROS)-mediated oxidative stress. To investigate this, THP-1 monocytic cells and primary human macrophages were co-stimulated with palmitate and TNF-α and mRNA and protein levels of MIP-1α were measured by using quantitative reverse transcription, polymerase chain reaction (qRT-PCR) and commercial enzyme-linked immunosorbent assays (ELISA), respectively. The cognate receptor of palmitate, toll-like receptor (TLR)-4, was blunted by genetic ablation, neutralization, and chemical inhibition. The involvement of TLR4-downstream pathways, interferon regulatory factor (IRF)-3 or myeloid differentiation (MyD)-88 factor, was determined using IRF3-siRNA or MyD88-deficient cells. Oxidative stress was induced in cells by hydrogen peroxide (H2O2) treatment and ROS induction was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. The data show that MIP-1α gene/protein expression was upregulated in cells co-stimulated with palmitate/TNF-α compared to those stimulated with either palmitate or TNF-α (P < 0.05). Further, TLR4-IRF3 pathway was implicated in the cooperative induction of MIP-1α in THP-1 cells, and this cooperativity between palmitate and TNF-α was clathrin-dependent and also required signaling through c-Jun and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Notably, ROS itself induced MIP-1α and could further promote MIP-1α secretion together with palmitate and TNF-α. In conclusion, palmitate and TNF-α co-induce MIP-1α in human monocytic cells via the TLR4-IRF3 pathway and signaling involving c-Jun/NF-κB. Importantly, oxidative stress leads to ROS-driven MIP-1α amplification, which may have significance for metabolic inflammation.
PKHhigh/CD133+/CD24− Renal Stem-Like Cells Isolated from Human Nephrospheres Exhibit In Vitro Multipotency
Authors: Bombelli Silvia , Meregalli Chiara , Grasselli Chiara , Bolognesi Maddalena M. , Bruno Antonino , Eriani Stefano , Torsello Barbara , De Marco Sofia , Bernasconi Davide P. , Zucchini Nicola , Mazzola Paolo , Bianchi Cristina , Grasso Marco , Albini Adriana , Cattoretti Giorgio , Perego Roberto A.
Published: July 2020

The mechanism upon which human kidneys undergo regeneration is debated, though different lineage-tracing mouse models have tried to explain the cellular types and the mechanisms involved. Different sources of human renal progenitors have been proposed, but it is difficult to argue whether these populations have the same capacities that have been described in mice. Using the nephrosphere (NS) model, we isolated the quiescent population of adult human renal stem-like PKHhigh/CD133+/CD24− cells (RSC). The aim of this study was to deepen the RSC in vitro multipotency capacity. RSC, not expressing endothelial markers, generated secondary nephrospheres containing CD31+/vWf+ cells and cytokeratin positive cells, indicating the coexistence of endothelial and epithelial commitment. RSC cultured on decellularized human renal scaffolds generated endothelial structures together with the proximal and distal tubular structures. CD31+ endothelial committed progenitors sorted from nephrospheres generated spheroids with endothelial-like sprouts in Matrigel. We also demonstrated the double commitment toward endothelial and epithelial lineages of single RSC. The ability of the plastic RSC population to recapitulate the development of tubular epithelial and endothelial renal lineages makes these cells a good tool for the creation of organoids with translational relevance for studying the parenchymal and endothelial cell interactions and developing new therapeutic strategies.
Fyn Tyrosine Kinase Elicits Amyloid Precursor Protein Tyr682 Phosphorylation in Neurons from Alzheimer’s Disease Patients
Authors: Iannuzzi Filomena , Sirabella Rossana , Canu Nadia , Maier Thorsten J. , Annunziato Lucio , Matrone Carmela
Published: July 2020

Alzheimer’s disease (AD) is an incurable neurodegenerative disorder with a few early detection strategies. We previously proposed the amyloid precursor protein (APP) tyrosine 682 (Tyr682) residue as a valuable target for the development of new innovative pharmacologic or diagnostic interventions in AD. Indeed, when APP is phosphorylated at Tyr682, it is forced into acidic neuronal compartments where it is processed to generate neurotoxic amyloid β peptides. Of interest, Fyn tyrosine kinase (TK) interaction with APP Tyr682 residue increases in AD neurons. Here we proved that when Fyn TK was overexpressed it elicited APP Tyr682 phosphorylation in neurons from healthy donors and promoted the amyloidogenic APP processing with Aβ peptides accumulation and neuronal death. Phosphorylation of APP at Tyr (pAPP-Tyr) increased in neurons of AD patients and AD neurons that exhibited high pAPP-Tyr also had higher Fyn TK activity. Fyn TK inhibition abolished the pAPP-Tyr and reduced Aβ42 secretion in AD neurons. In addition, the multidomain adaptor protein Fe65 controlled the Fyn-mediated pAPP-Tyr, warranting the possibility of targeting the Fe65-APP-Fyn pathway to develop innovative strategies in AD. Altogether, these results strongly emphasize the relevance of focusing on pAPP Tyr682 either for diagnostic purposes, as an early biomarker of the disease, or for pharmacological targeting, using Fyn TKI.
Nanotechnology as an Alternative to Reduce the Spread of COVID-19
Authors: Vazquez-Munoz Roberto , Lopez-Ribot Jose L.
Published: July 2020

The current emerging COVID-19 pandemic has caused a global impact on every major aspect of our societies. It is known that SARS-Cov-2 can endure harsh environmental conditions for up to 72 h, which may contribute to its rapid spread. Therefore, effective containment strategies, such as sanitizing, are critical. Nanotechnology can represent an alternative to reduce the COVID-19 spread, particularly in critical areas, such as healthcare facilities and public places. Nanotechnology-based products are effective at inhibiting different pathogens, including viruses, regardless of their drug-resistant profile, biological structure, or physiology. Although there are several approved nanotechnology-based antiviral products, this work aims to highlight the use of nanomaterials as sanitizers for the prevention of the spread of mainly SARS-Cov-2. It has been widely demonstrated that nanomaterials are an alternative for sanitizing surfaces to inactivate the virus. Also, antimicrobial nanomaterials can reduce the risk of secondary microbial infections on COVID-19 patients, as they inhibit the bacteria and fungi that can contaminate healthcare-related facilities. Finally, cost-effective, easy-to-synthesize antiviral nanomaterials could reduce the burden of the COVID-19 on challenging environments and in developing countries.
Upper Extremity Fractures in Children—Comparison between Worldwide, Romanian and Western Romanian Region Incidence
Authors: Adam Ovidiu , Horhat Florin George , Amaricai Elena , David Vlad-Laurentiu , Derzsi Zoltán , Boia Eugen Sorin
Published: July 2020

(1) Background: Fractures represent a significant part of all pediatric injuries, with distal forearm fracture being the most common fracture type in children. (2) Methods: In this comparative, epidemiological study we collected fracture incidence data from the scientific literature and compared it to real-world data extracted from the Romanian national and regional hospital database. In order to collect information on the epidemiology of upper extremity fractures in children, we conducted a systematic literature review on Medline, via PubMed. Extracted incidence data were stratified by fracture location, age or age interval and gender. Nationwide and Western Region incidence values were calculated for different fracture locations of the upper extremity using data extracted from a centralized hospital database. Incidence values were calculated using the mid-2018 census data. The search was restricted to the pediatric population. (3) Results: Incidence values for upper arm fractures nationwide and for Western Region were 54.83/100,000 person-years and 64.79/100,000 person-years, respectively. Forearm fractures had an incidence of 139.77/100,000 person-years and 139.56/100,000 person-years, respectively. The overall incidence of upper extremity fractures nationwide and for the Romanian Western Region were 206.02/100,000 person-years and 220.14/100,000 person-years, respectively. (4) Conclusions: Incidence of upper extremity fractures in the pediatric population varies according to the analyzed data. The calculated incidence depends on the site of fractures, assessed population (worldwide, Romanian population or regional-Western part of Romania) or patients’ age.
Preparation and Characterization of Self-Dispersing Phthalocyanine Blue 15:4 Pigment for Dyeing of Wool Textiles
Authors: Nie Lun , Chang Guangtao , Li Ruoxin
Published: July 2020

A self-dispersing pigment was produced by a diazonium coupling reaction; the pigment reacted with aromatic diazonium salts which were generated by the reaction of p-aminobenzene sulfonic acid and sodium nitrite. The surface of the pigment particles was negatively charged due to sulfonic acid groups on the pigment surface. The pigment particle size and zeta potential were, respectively, 134.5 nm and −45.4 mV at neutral pH. The wool surface was positively charged by adjusting the pH; then the anionic self-dispersing pigment dyed the cationic wool. The results show that self-dispersing pigment can adhere well without a binder, and that the K/S value is closely related to pH, dyeing time, and the amount of pigment. The color fastness of the wool was good and the light fastness of the wool was grade 5, which is better than acid dyes. Self-dispersing pigments are potential candidates for dyeing high-weather-resistance textiles.
Wear Behaviors of TiN/WS2 + hBN/NiCrBSi Self-Lubricating Composite Coatings on TC4 Alloy by Laser Cladding
Authors: Liu Kaiwei , Yan Hua , Zhang Peilei , Zhao Jian , Yu Zhishui , Lu Qinghua
Published: July 2020

TiN and WS2 + hBN reinforced Ni-based alloy self-lubricating composite coatings were fabricated on TC4 alloy by laser cladding using TiN, NiCrBSi, WS2, and hBN powder mixtures. Energy-dispersive spectroscopy (EDS), scanning electron microscopy (SEM), X-ray diffractometry (XRD), and optical microscopy (OM) were adopted to investigate the microstructure. The wear behaviors of the self-lubricating composite coatings were evaluated under large contact load in room temperature, dry-sliding wear-test conditions. Results indicated that the phases of the coatings mainly include γ-Ni, TiN, TiNi, TiW, WS2, and TiS mixtures. The average microhardness of the composite coating is 2.3–2.7 times that of the TC4 matrix. Laser cladding TiN/WS2 + hBN/NiCrBSi self-lubricating composite coatings revealed a higher wear resistance and lower friction coefficient than those of the TC4 alloy substrate. The friction coefficient (COF) of the coatings was oscillating around approximately 0.3458 due to the addition of self-lubricant WS2 + hBN and hard reinforcement TiN. The wear behaviors testing showed that the wear resistance of the as-received TC4 was significantly improved by a laser cladding TiN/WS2 + hBN/NiCrBSi self-lubricating composite coating.
Optimized CSIDH Implementation Using a 2-Torsion Point
Authors: Heo Donghoe , Kim Suhri , Yoon Kisoon , Park Young-Ho , Hong Seokhie
Published: July 2020

The implementation of isogeny-based cryptography mainly use Montgomery curves, as they offer fast elliptic curve arithmetic and isogeny computation. However, although Montgomery curves have efficient 3- and 4-isogeny formula, it becomes inefficient when recovering the coefficient of the image curve for large degree isogenies. Because the Commutative Supersingular Isogeny Diffie-Hellman (CSIDH) requires odd-degree isogenies up to at least 587, this inefficiency is the main bottleneck of using a Montgomery curve for CSIDH. In this paper, we present a new optimization method for faster CSIDH protocols entirely on Montgomery curves. To this end, we present a new parameter for CSIDH, in which the three rational two-torsion points exist. By using the proposed parameters, the CSIDH moves around the surface. The curve coefficient of the image curve can be recovered by a two-torsion point. We also proved that the CSIDH while using the proposed parameter guarantees a free and transitive group action. Additionally, we present the implementation result using our method. We demonstrated that our method is 6.4% faster than the original CSIDH. Our works show that quite higher performance of CSIDH is achieved while only using Montgomery curves.
Antiferroelectric Bent-Core Liquid Crystal for Possible High-Power Capacitors and Electrocaloric Devices
Authors: Saha Rony , Feng Chenrun , Eremin Alexey , Jákli Antal
Published: July 2020

We present small-angle X-ray scattering, polarized optical microscopy and electric current measurements of a sulfur-containing bent-core liquid crystal material for characterization of the layer and director structures, thermally and electrically driven transitions between antiferroelectric and ferroelectric structures and switching properties. It was found that the material has polarization-modulated homochiral synclinic ferroelectric (SmCsPFmod), homochiral anticlinic antiferroelectric (SmCaPA) and racemic synclininc antiferroelectric (SmCsPA) structures that can be reversibly switched between each other either thermally and/or electrically. High switching polarization combined with softness of the liquid crystalline structure makes this compound a good candidate for applications in high-power capacitors and electrocaloric devices.
Novel Molecular Resources to Facilitate Future Genetics Research on Freshwater Mussels (Bivalvia: Unionidae)
Authors: Johnson Nathan A. , Smith Chase H.
Published: July 2020

Molecular data have been an integral tool in the resolution of the evolutionary relationships and systematics of freshwater mussels, despite the limited number of nuclear markers available for Sanger sequencing. To facilitate future studies, we evaluated the phylogenetic informativeness of loci from the recently published anchored hybrid enrichment (AHE) probe set Unioverse and developed novel Sanger primer sets to amplify two protein-coding nuclear loci with high net phylogenetic informativeness scores: fem-1 homolog C (FEM1) and UbiA prenyltransferase domain-containing protein 1 (UbiA). We report the methods used for marker development, along with the primer sequences and optimized PCR and thermal cycling conditions. To demonstrate the utility of these markers, we provide haplotype networks, DNA alignments, and summary statistics regarding the sequence variation for the two protein-coding nuclear loci (FEM1 and UbiA). Additionally, we compare the DNA sequence variation of FEM1 and UbiA to three loci commonly used in freshwater mussel genetic studies: the mitochondrial genes cytochrome c oxidase subunit 1 (CO1) and NADH dehydrogenase subunit 1 (ND1), and the nuclear internal transcribed spacer 1 (ITS1). All five loci distinguish among the three focal species (Potamilus fragilis, Potamilus inflatus, and Potamilus purpuratus), and the sequence variation was highest for ND1, followed by CO1, ITS1, UbiA, and FEM1, respectively. The newly developed Sanger PCR primers and methodologies for extracting additional loci from AHE probe sets have great potential to facilitate molecular investigations targeting supraspecific relationships in freshwater mussels, but may be of limited utility at shallow taxonomic scales.
Early Onset Preeclampsia Diagnosis Prior to the 20th Week of Gestation in a Twin Pregnancy Managed via Selective Reduction of an Intrauterine Growth Restriction Fetus: A Case Report and Literature Review
Authors: Konstantopoulos Anastasios , Sfakianoudis Konstantinos , Simopoulou Mara , Kontogeorgi Adamantia , Rapani Anna , Grigoriadis Sokratis , Pantou Agni , Bathrellos Nikolaos , Grammatis Alexandros , Pantos Konstantinos
Published: July 2020

A single, healthy, 44-year-old perimenopausal woman pursuing a pregnancy, employed donor embryos, resulting to a dichorionic diamniotic twin pregnancy. In the 18th week of gestation severe symptoms indicated early onset preeclampsia reporting severe hypertension (BP 180/90 mmHg), intense headaches and nausea as well as elevated 24-h urine protein levels (1.5 g/day). Concurrently diagnosis of an IUGR fetus was concluded. Standard pharmaceutical administration for treating preeclampsia was ordered. Persistence of symptoms indicated recommendation for pregnancy termination, however the patient opted against this. Selective embryo reduction was performed as the last resort prior to pregnancy termination. Following selective reduction the headaches and nausea were successfully subdued and the patient’s blood pressure was adjusted (mean BP 130/80 mmHg). This enabled further progression of pregnancy for an impressive 11 week-period, and a live birth on the 30th week. To conclude, only a few rare cases have been reported with diagnosis of early onset preeclampsia prior to the 20th week mark and none report live births. Albeit termination of pregnancy was recommended, the management of selective reduction of the IUGR fetus enabled successful treatment of preeclampsia coupled by a live birth of a healthy infant without any perinatal or postnatal complications reported.
The Role of Imaging Biomarkers in the Assessment of Sarcopenia
Authors: Sanz-Requena Roberto , Martínez-Arnau Francisco Miguel , Pablos-Monzó Ana , Flor-Rufino Cristina , Barrachina-Igual Joaquín , García-Martí Gracián , Martí-Bonmatí Luis , Pérez-Ros Pilar
Published: July 2020

Background: The diagnosis of sarcopenia through clinical assessment has some limitations. The literature advises studies that include objective markers along with clinical assessment in order to improve the sensitivity and specificity of current diagnostic criteria. The decrease of muscle quality precedes the loss of quantity, so we studied the role magnetic resonance imaging biomarkers as indicators of the quantity and quality of muscle in sarcopenia patients. Methods: a cross-sectional analysis was performed to analyze what MR-derived imaging parameters correlate better with sarcopenia diagnostic criteria in women of 70 years of age and over (independent walking and community-dwelling women who were sarcopenic in accordance with EWGSOP criteria with muscle mass adjusted to Spanish population were chosen). Results: The study included 26 women; 81 ± 8 years old. A strong correlation was obtained between cineanthropometric variables (BMI; thigh perimeter and fat mass) and imaging biomarkers (muscle/fat ratio, fatty infiltration, muscle T2*, water diffusion coefficient, and proton density fat fraction) with coefficients around 0.7 (absolute value). Conclusions: Knowing the correlation of clinical parameters and imaging-derived muscle quality indicators can help to identify older women at risk of developing sarcopenia at an early stage. This may allow taking preventive actions to decrease disability, morbidity, and mortality in sarcopenia patients.