bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier
Authors: Furutama Daisuke , Matsuda Shinji , Yamawaki Yosuke , Hatano Saki , Okanobu Ai , Memida Takumi , Oue Hiroshi , Fujita Tsuyoshi , Ouhara Kazuhisa , Kajiya Mikihito , Mizuno Noriyoshi , Kanematsu Takashi , Tsuga Kazuhiro , Kurihara Hidemi
Published: September 2020

Background: Periodontal disease (PD) is a risk factor for systemic diseases, including neurodegenerative diseases. The role of the local and systemic inflammation induced by PD in neuroinflammation currently remains unclear. The present study investigated the involvement of periodontal inflammation in neuroinflammation and blood–brain barrier (BBB) disruption. Methods: To induce PD in mice (c57/BL6), a ligature was placed around the second maxillary molar. Periodontal, systemic, and neuroinflammation were assessed based on the inflammatory cytokine mRNA or protein levels using qPCR and ELISA. The BBB permeability was evaluated by the mRNA levels and protein levels of tight junction-related proteins in the hippocampus using qPCR and immunofluorescence. Dextran tracing in the hippocampus was also conducted to examine the role of periodontal inflammation in BBB disruption. Results: The TNF-α, IL-1β, and IL-6 levels markedly increased in gingival tissue 1 week after ligation. The IL-6 serum levels were also increased by ligature-induced PD. In the hippocampus, the IL-1β mRNA expression levels were significantly increased by ligature-induced PD through serum IL-6. The ligature-induced PD decreased the claudin 5 expression levels in the hippocampus, and the neutralization of IL-6 restored its levels. The extravascular 3-kDa dextran levels were increased by ligature-induced PD. Conclusions: These results suggest that the periodontal inflammation-induced expression of IL-6 is related to neuroinflammation and BBB disruption in the hippocampus, ultimately leading to cognitive impairment. Periodontal therapy may protect against neurodegenerative diseases.
Comparison of Modern Highly Interactive Flicker-Free Steady State Motion Visual Evoked Potentials for Practical Brain–Computer Interfaces
Authors: Stawicki Piotr , Volosyak Ivan
Published: September 2020

Motion-based visual evoked potentials (mVEP) is a new emerging trend in the field of steady-state visual evoked potentials (SSVEP)-based brain–computer interfaces (BCI). In this paper, we introduce different movement-based stimulus patterns (steady-state motion visual evoked potentials—SSMVEP), without employing the typical flickering. The tested movement patterns for the visual stimuli included a pendulum-like movement, a flipping illusion, a checkerboard pulsation, checkerboard inverse arc pulsations, and reverse arc rotations, all with a spelling task consisting of 18 trials. In an online experiment with nine participants, the movement-based BCI systems were evaluated with an online four-target BCI-speller, in which each letter may be selected in three steps (three trials). For classification, the minimum energy combination and a filter bank approach were used. The following frequencies were utilized: 7.06 Hz, 7.50 Hz, 8.00 Hz, and 8.57 Hz, reaching an average accuracy between 97.22% and 100% and an average information transfer rate (ITR) between 15.42 bits/min and 33.92 bits/min. All participants successfully used the SSMVEP-based speller with all types of stimulation pattern. The most successful SSMVEP stimulus was the SSMVEP1 (pendulum-like movement), with the average results reaching 100% accuracy and 33.92 bits/min for the ITR.
Three-Dimensional Cell Culture Systems in Radiopharmaceutical Cancer Research
Authors: Doctor Alina , Seifert Verena , Ullrich Martin , Hauser Sandra , Pietzsch Jens
Published: September 2020

In preclinical cancer research, three-dimensional (3D) cell culture systems such as multicellular spheroids and organoids are becoming increasingly important. They provide valuable information before studies on animal models begin and, in some cases, are even suitable for reducing or replacing animal experiments. Furthermore, they recapitulate microtumors, metastases, and the tumor microenvironment much better than monolayer culture systems could. Three-dimensional models show higher structural complexity and diverse cell interactions while reflecting (patho)physiological phenomena such as oxygen and nutrient gradients in the course of their growth or development. These interactions and properties are of great importance for understanding the pathophysiological importance of stromal cells and the extracellular matrix for tumor progression, treatment response, or resistance mechanisms of solid tumors. Special emphasis is placed on co-cultivation with tumor-associated cells, which further increases the predictive value of 3D models, e.g., for drug development. The aim of this overview is to shed light on selected 3D models and their advantages and disadvantages, especially from the radiopharmacist’s point of view with focus on the suitability of 3D models for the radiopharmacological characterization of novel radiotracers and radiotherapeutics. Special attention is paid to pancreatic ductal adenocarcinoma (PDAC) as a predestined target for the development of new radionuclide-based theranostics.
Targeted Inhibition of the NUP98-NSD1 Fusion Oncogene in Acute Myeloid Leukemia
Authors: Mohanty Sagarajit , Jyotsana Nidhi , Sharma Amit , Kloos Arnold , Gabdoulline Razif , Othman Basem , Lai Courteney K. , Schottmann Renate , Mandhania Madhvi , Schmoellerl Johannes , Grebien Florian , Ramsay Euan , Thomas Anitha , Vornlocher Hans-Peter , Ganser Arnold , Thol Felicitas , Heuser Michael
Published: September 2020

NUP98-NSD1-positive acute myeloid leukemia (AML) is a poor prognostic subgroup that is frequently diagnosed in pediatric cytogenetically normal AML. NUP98-NSD1-positive AML often carries additional mutations in genes including FLT3, NRAS, WT1, and MYC. The purpose of our study was to characterize the cooperative potential of the fusion and its associated Neuroblastoma rat sarcoma (NRAS) mutation. By constitutively expressing NUP98-NSD1 and NRASG12D in a syngeneic mouse model and using a patient-derived xenograft (PDX) model from a NUP98-NSD1-positive AML patient, we evaluated the functional role of these genes and tested a novel siRNA formulation that inhibits the oncogenic driver NUP98-NSD1. NUP98-NSD1 transformed murine bone marrow (BM) cells in vitro and induced AML in vivo. While NRASG12D expression was insufficient to transform cells alone, co-expression of NUP98-NSD1 and NRASG12D enhanced the leukemogenicity of NUP98-NSD1. We developed a NUP98-NSD1-targeting siRNA/lipid nanoparticle formulation that significantly prolonged the survival of the PDX mice. Our study demonstrates that mutated NRAS cooperates with NUP98-NSD1 and shows that direct targeting of the fusion can be exploited as a novel treatment strategy in NUP98-NSD1-positive AML patients.
Immune Checkpoint Inhibitors in Uro-Oncology: Urgent Call for Biomarkers
Authors: Pichler Renate
Published: September 2020

Bladder cancer and renal cell carcinoma (RCC) are the second and third most commonly diagnosed cancers in the field of uro-oncology [...]
Identification of Genes Whose Expression Overlaps Age Boundaries and Correlates with Risk Groups in Paediatric and Adult Acute Myeloid Leukaemia
Authors: Davis Lindsay , Mills Ken I. , Orchard Kim H. , Guinn Barbara-Ann
Published: September 2020

Few studies have compared gene expression in paediatric and adult acute myeloid leukaemia (AML). In this study, we have analysed mRNA-sequencing data from two publicly accessible databases: (1) National Cancer Institute’s Therapeutically Applicable Research to Generate Effective Treatments (NCI-TARGET), examining paediatric patients, and (2) The Cancer Genome Atlas (TCGA), examining adult patients with AML. With a particular focus on 144 known tumour antigens, we identified STEAP1, SAGE1, MORC4, SLC34A2 and CEACAM3 as significantly different in their expression between standard and low risk paediatric AML patient subgroups, as well as between poor and good, and intermediate and good risk adult AML patient subgroups. We found significant differences in event-free survival (EFS) in paediatric AML patients, when comparing standard and low risk subgroups, and quartile expression levels of BIRC5, MAGEF1, MELTF, STEAP1 and VGLL4. We found significant differences in EFS in adult AML patients when comparing intermediate and good, and poor and good risk adult AML patient subgroups and quartile expression levels of MORC4 and SAGE1, respectively. When examining Kyoto Encyclopedia of Genes and Genomes (KEGG) (2016) pathway data, we found that genes altered in AML were involved in key processes such as the evasion of apoptosis (BIRC5, WNT1) or the control of cell proliferation (SSX2IP, AML1-ETO). For the first time we have compared gene expression in paediatric AML patients with that of adult AML patients. This study provides unique insights into the differences and similarities in the gene expression that underlies AML, the genes that are significantly differently expressed between risk subgroups, and provides new insights into the molecular pathways involved in AML pathogenesis.
Cancer Predisposition Genes in Cancer-Free Families
Authors: Zheng Guoqiao , Catalano Calogerina , Bandapalli Obul Reddy , Paramasivam Nagarajan , Chattopadhyay Subhayan , Schlesner Matthias , Sijmons Rolf , Hemminki Akseli , Dymerska Dagmara , Lubinski Jan , Hemminki Kari , Försti Asta
Published: September 2020

Familial clustering, twin concordance, and identification of high- and low-penetrance cancer predisposition variants support the idea that there are families that are at a high to moderate excess risk of cancer. To what extent there may be families that are protected from cancer is unknown. We wanted to test genetically whether cancer-free families share fewer breast, colorectal, and prostate cancer risk alleles than the population at large. We addressed this question by whole-genome sequencing (WGS) of 51 elderly cancer-free individuals whose numerous (ca. 1000) family members were found to be cancer-free (‘cancer-free families’, CFFs) based on face-to-face interviews. The average coverage of the 51 samples in the WGS was 42x. We compared cancer risk allele frequencies in cancer-free individuals with those in the general population available in public databases. The CFF members had fewer loss-of-function variants in suggested cancer predisposition genes compared to the ExAC data, and for high-risk cancer predisposition genes, no pathogenic variants were found in CFFs. For common low-penetrance breast, colorectal, and prostate cancer risk alleles, the results were not conclusive. The results suggest that, in line with twin and family studies, random environmental causes are so dominant that a clear demarcation of cancer-free populations using genetic data may not be feasible.
Non-Invasive Early Detection of Oral Cancers Using Fluorescence Visualization with Optical Instruments
Authors: Morikawa Takamichi , Shibahara Takahiko , Nomura Takeshi , Katakura Akira , Takano Masayuki
Published: September 2020

Background: Oral cancer screening is important for early detection and early treatment, which help improve survival rates. Biopsy is the gold standard for a definitive diagnosis but is invasive and painful, while fluorescence visualization is non-invasive, convenient, and real-time, and examinations can be repeated using optical instruments. The purpose of this study was to clarify the usefulness of fluorescence visualization in oral cancer screening. Methods: A total of 502 patients, who were examined using fluorescence visualization with optical instruments in our hospitals between 2014 and 2019, were enrolled in this study. The final diagnosis was performed by pathological examination. Fluorescence visualization was analyzed using subjective and objective evaluations. Results: Subjective evaluations for detecting oral cancer offered 96.8% sensitivity and 48.4% specificity. Regarding the objective evaluations, sensitivity and specificity were 43.7% and 84.6% for mean green value, 55.2% and 67.0% for median green value, 82.0% and 44.2% for coefficient of variation of value, 59.6% and 45.3% for skewness, and 85.1% and 75.8% for value ratio. For the sub-analysis of oral cancer, all factors on objective and subjective evaluation showed no significant difference. Conclusions: Fluorescence visualization with subjective and objective evaluation is useful for oral cancer screening.
tRNA-Derived Small RNAs: Novel Epigenetic Regulators
Authors: Park Joonhyeong , Ahn Se Hee , Shin Myung Geun , Kim Hak Kyun , Chang Suhwan
Published: September 2020

An epigenetic change is a heritable genetic alteration that does not involve any nucleotide changes. While the methylation of specific DNA regions such as CpG islands or histone modifications, including acetylation or methylation, have been investigated in detail, the role of small RNAs in epigenetic regulation is largely unknown. Among the many types of small RNAs, tRNA-derived small RNAs (tsRNAs) represent a class of noncoding small RNAs with multiple roles in diverse physiological processes, including neovascularization, sperm maturation, immune modulation, and stress response. Regarding these roles, several pioneering studies have revealed that dysregulated tsRNAs are associated with human diseases, such as systemic lupus, neurological disorder, metabolic disorder, and cancer. Moreover, recent findings suggest that tsRNAs regulate the expression of critical genes linked with these diseases by a variety of mechanisms, including epigenetic regulation. In this review, we will describe different classes of tsRNAs based on their biogenesis and will focus on their role in epigenetic regulation.
Hepatocellular Carcinoma and Non-Alcoholic Fatty Liver Disease: A Step Forward for Better Evaluation Using Ultrasound Elastography
Authors: Lupsor-Platon Monica , Serban Teodora , Silion Alexandra-Iulia , Tirpe Alexandru , Florea Mira
Published: September 2020

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population prompts for a quick response from physicians. As NAFLD can progress to liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC), new non-invasive, rapid, cost-effective diagnostic methods are needed. In this review, we explore the diagnostic performance of ultrasound elastography for non-invasive assessment of NAFLD and NAFLD-related HCC. Elastography provides a new dimension to the conventional ultrasound examination, by adding the liver stiffness quantification in the diagnostic algorithm. Whilst the most efficient elastographic techniques in staging liver fibrosis in NAFLD are vibration controlled transient elastography (VCTE) and 2D-Shear wave elastography (2D-SWE), VCTE presents the upside of assessing steatosis through the controlled attenuation parameter (CAP). Hereby, we have also critically reviewed the most important elastographic techniques for the quantitative characterization of focal liver lesions (FLLs), focusing on HCC: Point shear wave elastography (pSWE) and 2D-SWE. As our paper shows, elastography should not be considered as a substitute for FLL biopsy because of the stiffness values overlap. Furthermore, by using non-invasive, disease-specific surveillance tools, such as US elastography, a subset of the non-cirrhotic NAFLD patients at risk for developing HCC can be detected early, leading to a better outcome. A recent ultrasomics study exemplified the wide potential of 2D-SWE to differentiate benign FLLs from malignant ones, guiding the clinician towards the next steps of diagnosis and contributing to better long-term disease surveillance.
Geriatric Nutritional Risk Index Less Than 92 Is a Predictor for Late Postpancreatectomy Hemorrhage Following Pancreatoduodenectomy: A Retrospective Cohort Study
Authors: Funamizu Naotake , Omura Kenji , Takada Yasutsugu , Ozaki Takahiro , Mishima Kohei , Igarashi Kazuharu , Wakabayashi Go
Published: September 2020

Postpancreatectomy hemorrhage (PPH) is the most lethal complication of pancreatoduodenectomy (PD). The main risk factor for PPH is the development of a postoperative pancreatic fistula (POPF). Recent evidence shows that the geriatric nutritional risk index (GNRI) may be predictive indicator for POPF. In this study, we aimed to evaluate whether GNRI is a reliable predictive marker for PPH following PD. The present study retrospectively evaluated 121 patients treated with PD at Ageo Central General Hospital in Japan between January 2015 and March 2020. We investigated the potential of age, gender, body mass index, serum albumin, American Society of Anesthesiologists classification (ASA), diabetes mellitus and smoking status, time taken for the operation, estimated blood loss, and postoperative complications (POPF, bile leak, and surgical site infections) to predict the risk of PPH following PD using univariate and multivariate analyses. Ten patients had developed PPH with an incidence of 8.3%. Among them, the patients were divided into bleeding group (n = 10) and non-bleeding group (n = 111). The bleeding group had significantly lower GNRI values than those in the non-bleeding group (p = 0.001). We determined that the cut-off value of GNRI was 92 accounting for a sensitivity 80.0%, specificity 82.9%, and likelihood ratio of 4.6 using receiver operating characteristic curve analysis. A GNRI of <92 was statistically associated with PPH in both univariate (p < 0.001) and multivariate analysis (p = 0.01). Therefore, we could identify that a GNRI < 92 was an independently potential predictor of PPH risk following PD. We should alert surgeons if patients have low level GNRI before PD.
Cold Atmospheric Plasma Treatment for Pancreatic Cancer–The Importance of Pancreatic Stellate Cells
Authors: Verloy Ruben , Privat-Maldonado Angela , Smits Evelien , Bogaerts Annemie
Published: September 2020

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with low five-year survival rates of 8% by conventional treatment methods, e.g., chemotherapy, radiotherapy, and surgery. PDAC shows high resistance towards chemo- and radiotherapy and only 15–20% of all patients can have surgery. This disease is predicted to become the third global leading cause of cancer death due to its significant rise in incidence. Therefore, the development of an alternative or combinational method is necessary to improve current approaches. Cold atmospheric plasma (CAP) treatments could offer multiple advantages to this emerging situation. The plasma-derived reactive species can induce oxidative damage and a cascade of intracellular signaling pathways, which could lead to cell death. Previous reports have shown that CAP treatment also influences cells in the tumor microenvironment, such as the pancreatic stellate cells (PSCs). These PSCs, when activated, play a crucial role in the propagation, growth and survival of PDAC tumors. However, the effect of CAP on PSCs is not yet fully understood. This review focuses on the application of CAP for PDAC treatment and the importance of PSCs in the response to treatment.
Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies
Authors: Wei Qi-Yao , Xu Yan-Ming , Lau Andy T. Y.
Published: September 2020

Conventional chemotherapy is still an important option of cancer treatment, but it has poor cell selectivity, severe side effects, and drug resistance. Utilizing nanoparticles (NPs) to improve the therapeutic effect of chemotherapeutic drugs has been highlighted in recent years. Nanotechnology dramatically changed the face of oncology by high loading capacity, less toxicity, targeted delivery of drugs, increased uptake to target sites, and optimized pharmacokinetic patterns of traditional drugs. At present, research is being envisaged in the field of novel nano-pharmaceutical design, such as liposome, polymer NPs, bio-NPs, and inorganic NPs, so as to make chemotherapy effective and long-lasting. Till now, a number of studies have been conducted using a wide range of nanocarriers for the treatment of solid tumors including lung, breast, pancreas, brain, and liver. To provide a reference for the further application of chemodrug-loaded nanoformulations, this review gives an overview of the recent development of nanocarriers, and the updated status of their use in the treatment of several solid tumors.
Efficient Propagation of Circulating Tumor Cells: A First Step for Probing Tumor Metastasis
Authors: Xiao Jerry , McGill Joseph R. , Stanton Kelly , Kassner Joshua D. , Choudhury Sujata , Schlegel Richard , Sauna Zuben E. , Pohlmann Paula R. , Agarwal Seema
Published: September 2020

Circulating tumor cells (CTCs) represent a unique population of cells that can be used to investigate the mechanistic underpinnings of metastasis. Unfortunately, current technologies designed for the isolation and capture of CTCs are inefficient. Existing literature for in vitro CTC cultures report low (6−20%) success rates. Here, we describe a new method for the isolation and culture of CTCs. Once optimized, we employed the method on 12 individual metastatic breast cancer patients and successfully established CTC cultures from all 12 samples. We demonstrate that cells propagated were of breast and epithelial origin. RNA-sequencing and pathway analysis demonstrated that CTC cultures were distinct from cells obtained from healthy donors. Finally, we observed that CTC cultures that were associated with CD45+ leukocytes demonstrated higher viability. The presence of CD45+ leukocytes significantly enhanced culture survival and suggests a re-evaluation of the methods for CTC isolation and propagation. Routine access to CTCs is a valuable resource for identifying genetic and molecular markers of metastasis, personalizing the treatment of metastatic cancer patients and developing new therapeutics to selectively target metastatic cells.
β-Cyclodextrin-Silica Hybrid: A Spatially Controllable Anchoring Strategy for Cu(II)/Cu(I) Complex Immobilization
Authors: Calsolaro Federica , Martina Katia , Borfecchia Elisa , Chávez-Rivas Fernando , Cravotto Giancarlo , Berlier Gloria
Published: September 2020

The development of new strategies for spatially controllable immobilization has encouraged the preparation of novel catalysts based on the organic-inorganic hybrid concept. In the present paper, a Cu-based multi-structured silica catalyst has been prepared and fully characterized. The inclusion of Cu(II) in β-cyclodextrins has been exploited with the double aim to stabilize the metal and to act as a source of Cu(I) catalytic sites. Multi-technique characterization by infrared, UV-visible, electron microscopy and X-ray absorption spectroscopies of the fresh and exhaust catalysts provided information on the local structure, redox properties and stability of the investigated hybrid systems. The catalytic system showed that copper nanospecies were dispersed on the support and hardly affected by the catalytic tests, confirming the stabilizing effect of β-CD, and likely of the N1-(3-Trimethoxysilylpropyl) diethylenetriamine spacer, as deduced by X-ray absorption spectroscopy analysis. Overall, we demonstrate a feasible approach to efficiently anchor Cu(II) species and to obtain a reusable single-site hybrid catalyst well suited for Cu(I)-catalyzed alkyne-azide cycloaddition.
Doping of Graphitic Carbon Nitride with Non-Metal Elements and Its Applications in Photocatalysis
Authors: Starukh Halyna , Praus Petr
Published: September 2020

This review outlines the latest research into the design of graphitic carbon nitride (g-C3N4) with non-metal elements. The emphasis is put on modulation of composition and morphology of g-C3N4 doped with oxygen, sulfur, phosphor, nitrogen, carbon as well as nitrogen and carbon vacancies. Typically, the various methods of non-metal elements introducing in g-C3N4 have been explored to simultaneously tune the textural and electronic properties of g-C3N4 for improving its response to the entire visible light range, facilitating a charge separation, and prolonging a charge carrier lifetime. The application fields of such doped graphitic carbon nitride are summarized into three categories: CO2 reduction, H2-evolution, and organic contaminants degradation. This review shows some main directions and affords to design the g-C3N4 doping with non-metal elements for real photocatalytic applications.
Astrocytic Factors Controlling Synaptogenesis: A Team Play
Authors: Fossati Giuliana , Matteoli Michela , Menna Elisabetta
Published: September 2020

Astrocytes are essential players in brain circuit development and homeostasis, controlling many aspects of synapse formation, function, plasticity and elimination both during development and adulthood. Accordingly, alterations in astrocyte morphogenesis and physiology may severely affect proper brain development, causing neurological or neuropsychiatric conditions. Recent findings revealed a huge astrocyte heterogeneity among different brain areas, which is likely at the foundation of the different synaptogenic potential of these cells in selected brain regions. This review highlights recent findings on novel mechanisms that regulate astrocyte-mediated synaptogenesis during development, and the control of synapse number in the critical period or upon synaptic plasticity.
Integrated Transcriptome and Proteome Analyses Reveal the Regulatory Role of miR-146a in Human Limbal Epithelium via Notch Signaling
Authors: Poe Adam J. , Kulkarni Mangesh , Leszczynska Aleksandra , Tang Jie , Shah Ruchi , Jami-Alahmadi Yasaman , Wang Jason , Kramerov Andrei A. , Wohlschlegel James , Punj Vasu , Ljubimov Alexander V. , Saghizadeh Mehrnoosh
Published: September 2020

MiR-146a is upregulated in the stem cell-enriched limbal region vs. central human cornea and can mediate corneal epithelial wound healing. The aim of this study was to identify miR-146a targets in human primary limbal epithelial cells (LECs) using genomic and proteomic analyses. RNA-seq combined with quantitative proteomics based on multiplexed isobaric tandem mass tag labeling was performed in LECs transfected with miR-146a mimic vs. mimic control. Western blot and immunostaining were used to confirm the expression of some targeted genes/proteins. A total of 251 differentially expressed mRNAs and 163 proteins were identified. We found that miR-146a regulates the expression of multiple genes in different pathways, such as the Notch system. In LECs and organ-cultured corneas, miR-146a increased Notch-1 expression possibly by downregulating its inhibitor Numb, but decreased Notch-2. Integrated transcriptome and proteome analyses revealed the regulatory role of miR-146a in several other processes, including anchoring junctions, TNF-α, Hedgehog signaling, adherens junctions, TGF-β, mTORC2, and epidermal growth factor receptor (EGFR) signaling, which mediate wound healing, inflammation, and stem cell maintenance and differentiation. Our results provide insights into the regulatory network of miR-146a and its role in fine-tuning of Notch-1 and Notch-2 expressions in limbal epithelium, which could be a balancing factor in stem cell maintenance and differentiation.
Neuron-Glia Interactions in Neurodevelopmental Disorders
Authors: Kim Yoo Sung , Choi Juwon , Yoon Bo-Eun
Published: September 2020

Recent studies have revealed synaptic dysfunction to be a hallmark of various psychiatric diseases, and that glial cells participate in synapse formation, development, and plasticity. Glial cells contribute to neuroinflammation and synaptic homeostasis, the latter being essential for maintaining the physiological function of the central nervous system (CNS). In particular, glial cells undergo gliotransmission and regulate neuronal activity in tripartite synapses via ion channels (gap junction hemichannel, volume regulated anion channel, and bestrophin-1), receptors (for neurotransmitters and cytokines), or transporters (GLT-1, GLAST, and GATs) that are expressed on glial cell membranes. In this review, we propose that dysfunction in neuron-glia interactions may contribute to the pathogenesis of neurodevelopmental disorders. Understanding the mechanisms of neuron-glia interaction for synapse formation and maturation will contribute to the development of novel therapeutic targets of neurodevelopmental disorders.
GPR91 Receptor Mediates Protection against Doxorubicin-Induced Cardiotoxicity without Altering Its Anticancer Efficacy. An In Vitro Study on H9C2 Cardiomyoblasts and Breast Cancer-Derived MCF-7 Cells
Authors: Dallons Matthieu , Alpan Esma , Schepkens Corentin , Tagliatti Vanessa , Colet Jean-Marie
Published: September 2020

Doxorubicin (DOX) is an anticancer drug widely used in oncology, especially for breast cancer. The main limitation of DOX treatment is its cardiotoxicity due to the cumulative dose. Clinically, DOX-induced cardiomyopathy develops as a progressive heart failure caused by a progressive cardiomyocyte’s death. For long, the oxidative stress induced by DOX was considered as the main toxic mechanism responsible for heart damage, but it is now controverted, and other processes are investigated to develop cardioprotective strategies. Previously, we studied DOX-induced cardiotoxicity and dexrazoxane (DEX), the only cardioprotective compound authorized by the FDA, by 1H-NMR metabonomics in H9C2 cells. We observed an increased succinate secretion in the extracellular fluid of DEX-exposed cardiomyocytes, a finding that led us to the hypothesis of a possible protective role of this agonist of the GPR91 receptor. The objective of the present work was to study the effect of succinate (SUC) and cis-epoxysuccinate (cis-ES), two agonists of the GPR91 receptor, on DOX-induced cardiotoxicity to H9C2 cells. To this purpose, several toxicity parameters, including cell viability, oxidative stress and apoptosis, as well as the GPR91 expression, were measured to assess the effects of DEX, SUC and cis-ES either alone or in combination with DOX in H9C2 cells. A 1H-NMR-based metabonomic study was carried out on cellular fluids collected after 24 h to highlight the metabolic changes induced by those protective compounds. Moreover, the effects of each agonist given either alone or in combination with DOX were evaluated on MCF-7 breast cancer cells. GPR91 expression was confirmed in H9C2 cells, while no expression was found in MCF-7 cells. Under such experimental conditions, both SUC and cis-ES decreased partially the cellular mortality, the oxidative stress and the apoptosis induced by DOX. The SUC protective effect was similar to the DEX effect, but the protective effect of cis-ES was higher on oxidative stress and apoptosis. In addition, the metabonomics findings pointed out several metabolic pathways involved in the cardioprotective effects of both GPR91 agonists: the stimulation of aerobic metabolism with glucose as the main fuel, redox balance and phospholipids synthesis. Finally, none of the GPR91 agonists jeopardized the pharmacological effects of DOX on MCF-7 breast cancer cells.
Serum Levels of Bone Morphogenetic Proteins 2 and 4 in Patients with Acute Myocardial Infarction
Authors: Kercheva Maria , Gusakova Anna M. , Ryabova Tamara R. , Suslova Tatiana E. , Kzhyshkowska Julia , Ryabov Vyacheslav V.
Published: September 2020

Background: Bone morphogenetic proteins-2 and -4 (BMPs) have been implicated in left ventricular remodeling (LVR) processes such as an inflammation and fibrogenesis. We hypothesized that this knowledge could be translated into clinics. Methods: We studied the dynamics of serum levels of BMPs, its correlation with markers of LVR and with parameters of echocardiography in patients (n = 31) during the six-month follow-up period after myocardial infarction (MI). Results: Elevated serum levels of BMPs decreased by the six-month follow-up period. BMP-2 decreased from the first day after MI, and BMP-4 decreased from the Day 14. The elevated level of BMP-2 at Day 1 was associated with a lower level of troponin I, reperfusion time and better left ventricular ejection fraction (LV EF) at the six-month follow-up. Elevated serum level of BMP-4 at Day 1 was associated with a lower level of a soluble isoform of suppression of tumorigenicity 2 (sST2), age and reperfusion time. An elevated level of BMP-2 at the six-month follow-up was associated with higher levels of BMP-4, high-sensitivity C-reactive protein (hCRP) and sST2. High serum level of BMP-2 correlated with high levels of hCRP and matrix metalloproteinase (MMP)-9 on Day 7. High serum level of BMP-4 correlated with low levels of hCRP, MMP-9 at Day 3, sST2 at Day 1 and with decreased LV EF on Day 7. The findings of multivariate analysis support the involvement of BMP-2 in the development of post-infarction LVR. Conclusions: Our research translates experimental data about the BMPs in the development of adverse LVR into the clinic. Elevated serum levels of BMPs decreased by the end of the six-month period after MI. BMP-2 decreased from the first day and BMP-4 decreased from Day 14. BMP-2 and BMP-4 were associated with the development of LVR. Their correlations with markers of inflammation, degradation of the extracellular matrix, hemodynamic stress and markers of myocardial damage further support our hypothesis. Diagnostic and predictive values of these BMPs at the development of post-infarction LVR in vivo should be investigated further.
Control of Cell Identity by the Nuclear Receptor HNF4 in Organ Pathophysiology
Authors: Dubois Vanessa , Staels Bart , Lefebvre Philippe , Verzi Michael , Eeckhoute Jérôme
Published: September 2020

Hepatocyte Nuclear Factor 4 (HNF4) is a transcription factor (TF) belonging to the nuclear receptor family whose expression and activities are restricted to a limited number of organs including the liver and gastrointestinal tract. In this review, we present robust evidence pointing to HNF4 as a master regulator of cellular differentiation during development and a safekeeper of acquired cell identity in adult organs. Importantly, we discuss that transient loss of HNF4 may represent a protective mechanism upon acute organ injury, while prolonged impairment of HNF4 activities could contribute to organ dysfunction. In this context, we describe in detail mechanisms involved in the pathophysiological control of cell identity by HNF4, including how HNF4 works as part of cell-specific TF networks and how its expression/activities are disrupted in injured organs.
Role of Vitamin K-Dependent Factors Protein S and GAS6 and TAM Receptors in SARS-CoV-2 Infection and COVID-19-Associated Immunothrombosis
Authors: Tutusaus Anna , Marí Montserrat , Ortiz-Pérez José T. , Nicolaes Gerry A. F. , Morales Albert , García de Frutos Pablo
Published: September 2020

The vitamin K-dependent factors protein S (PROS1) and growth-arrest-specific gene 6 (GAS6) and their tyrosine kinase receptors TYRO3, AXL, and MERTK, the TAM subfamily of receptor tyrosine kinases (RTK), are key regulators of inflammation and vascular response to damage. TAM signaling, which has largely studied in the immune system and in cancer, has been involved in coagulation-related pathologies. Because of these established biological functions, the GAS6-PROS1/TAM system is postulated to play an important role in SARS-CoV-2 infection and progression complications. The participation of the TAM system in vascular function and pathology has been previously reported. However, in the context of COVID-19, the role of TAMs could provide new clues in virus-host interplay with important consequences in the way that we understand this pathology. From the viral mimicry used by SARS-CoV-2 to infect cells, to the immunothrombosis that is associated with respiratory failure in COVID-19 patients, TAM signaling seems to be involved at different stages of the disease. TAM targeting is becoming an interesting biomedical strategy, which is useful for COVID-19 treatment now, but also for other viral and inflammatory diseases in the future.
A Review of Green Scale Inhibitors: Process, Types, Mechanism and Properties
Authors: Jafar Mazumder Mohammad A.
Published: September 2020

In the present time, more often, it has been seen that scaling has grown as widely and caused problems in the oilfield industry. Scaling is the deposition of various salts of inorganic/organic materials due to the supersaturation of salt-water mixtures. Many works have been proposed by researchers using different methods to solve the problem, of which scale inhibition is one of them. The scale inhibitors, particularly for antiscaling, have derived from natural and synthetic polymers. Among different polymers, inorganic and organic compounds (polyphosphates, carboxylic acid, ethylenediaminetetraacetic acid (EDTA), etc.) can effectively manage the oilfield scales of which many are toxic and expansive. Scale inhibitors of alkaline earth metal carbonate and sulfates and transition metal sulfide are commonly used in oilfield applications. Scale inhibition of metallic surfaces is an essential activity in technical, environmental, economic, and safety purposes. Scale inhibitors containing phosphorus appear to have significant achievements in the inhibition process despite its toxicity. However, phosphorus-based inhibitors can serve as supplements prompting eutrification difficulties. Besides these increasing environmental concerns, green scale inhibitors are renewable, biodegradable, and ecologically acceptable that has been used to prevent, control, and retard the formation of scale. Considering the facts, this review article summarized the concept of scale, various green scale inhibitors, types, mechanisms, comparative performance, significance, and future aspects of green scale inhibitors, which will shed light and be helpful for the professionals working in the oil and gas industries.
Assessing the Sustainability and Acceptance Rate of Cost-Effective Household Water Treatment Systems in Rural Communities of Makwane Village, South Africa
Authors: Moropeng Resoketswe Charlotte , Momba Maggy Ndombo Benteke
Published: September 2020

The current study investigated the acceptance rate and long-term effectiveness of cost-effective household water treatment systems deployed in Makwane Village. A structured questionnaire was used prior to implementation to collect information such as level of education, level of employment, and knowledge about point-of-use water treatment systems in the target area. The long-term effectiveness was determined by factors such as the Escherichia coli removal efficiency, turbidity reduction, silver leached, and flow rate of the household water treatment devices. The results of the survey prior to deployment revealed that only 4.3% of the community had a tertiary qualification. Moreover, 54.3% of the community were unemployed. The results further revealed that 65.9% of the community were knowledgeable about other point-of-use water treatment methods. The acceptance rate, which was found to be initially higher (100%), reduced after three months of implantation (biosand filter with zeolite-silver clay granular—82.9%; silver-impregnated porous pot filters—97.1%). Moreover, the long-term effectiveness was determined, taking into consideration the adoption rate, and it was found that silver-impregnated porous pot filters have a long life compared to biosand filter with zeolite-silver clay granular. Although household water treatment systems can effectively reduce the burden of waterborne diseases in impoverished communities, the success of adoption is dependent on the targeted group. This study highlights the significance of involving community members when making the decision to scale up household water treatment devices in rural areas for successful adoption.
Cationically Modified Nanocrystalline Cellulose/Carboxyl-Functionalized Graphene Quantum Dots Nanocomposite Thin Film: Characterization and Potential Sensing Application
Authors: Rosddi Najwa Norimanina Muhammad , Fen Yap Wing , Anas Nur Ain Asyiqin , Omar Nur Alia Sheh , Ramdzan Nur Syahira Md , Daniyal Wan Mohd Ebtisyam Mustaqim Mohd
Published: September 2020

In this study, highly functional cationically modified nanocrystalline cellulose (NCC)/carboxyl-functionalized graphene quantum dots (CGQD) has been described. The surface of NCC was first modified with hexadecyltrimethylammonium bromide (CTA) before combining with CGQD. The CGQD, CTA-NCC and CTA-NCC/CGQD nanocomposites thin films were prepared using spin coating technique. The obtained nanocomposite thin films were then characterized by using the Fourier transform infrared spectroscopy (FTIR) which confirmed the existence of hydroxyl groups, carboxyl groups and alkyl groups in CTA-NCC/CGQD. The optical properties of the thin films were characterized using UV–Vis spectroscopy. The absorption of CTA-NCC/CGQD was high with an optical band gap of 4.127 eV. On the other hand, the CTA-NCC/CGQD nanocomposite thin film showed positive responses towards glucose solution of different concentration using an optical method based on surface plasmon resonance phenomenon. This work suggests that the novel nanocomposite thin film has potential for a sensing application in glucose detection.
Artificial Wetlands as Breeding Habitats for Colonial Waterbirds within Central Romania
Authors: Ionescu Dan Traian , Hodor Călin Vasile , Petritan Ion Cătălin
Published: September 2020

The historical loss of natural wetlands in Romania is significant. The building of lakes, ponds, and dams has compensated for some of these losses, as was the case in the study area, the artificial wetlands designated as the Natura 2000 (special protection area, SPA) and Ramsar sites. In this context, to evaluate the conservation status of colonial waterbirds (cormorants, herons, and egrets), we analyzed actual distributions, habitat selection, features, and population sizes. Standardized counting of colonial species was used, supplemented by nest counting and colony-area estimation during winter, and drone footage. All species and their colonies were built in artificial or anthropically influenced habitats. Concerning distribution and population sizes, Phalacrocorax carbo and Microcarbo pygmeus were found to nest only in central Romania. The pair numbers of Ardea alba, Ardea purpurea, Ardea cinerea, and Nycticorax nycticorax in the area exceeded 1% of the national minimum breeding population. There was a statistically significant positive trend of breeding populations for Ardea alba, Nycticorax nycticorax, and Egretta garzetta. In conclusion, these artificial wetlands offer optimal breeding conditions for a relatively large diversity of colonial bird species over areas that are not very large.
Effects of Temperature and pH on the Egg Production and Hatching Success of a Common Korean Copepod
Authors: Lee Eun Hye , Choi Seo Yeol , Seo Min Ho , Lee Seok Ju , Soh Ho Young
Published: September 2020

The recent accelerated ocean acidification and global warming caused by increased atmospheric carbon dioxide may have an impact on the physiology and ecology of marine animals. This study was conducted to determine the egg production rate (EPR) and hatching success (EHS) of Acartia ohtsukai in response to the combined effects of an increase in temperature and a lower pH. Acartiaohtsukai with fresh surface seawater were collected in the northwestern Yeoja Bay of Korea in September 2017. The temperature and pH conditions applied included two different pH levels (representing the present: 7.9 and the future: 7.6) and three temperature values (26 °C, 28 °C, and 30 °C). In the pH 7.9, EPR significantly increased with increased temperature, but in pH 7.6, it significantly decreased as the temperature increased. EHS was lower in pH 7.6 than in pH 7.9. These results suggest that changes in the marine environment due to global warming and ocean acidification may affect Acartia populations and cause overall fluctuations in copepods of the genus Acartia.
Harvesting Criteria Application as a Technical and Financial Alternative for Management of Degraded Tropical Forests: A Case Study from Brazilian Amazon
Authors: Siviero Marco A. , Ruschel Ademir R. , Yared Jorge A. G. , de Aguiar Osmar J. R. , Pereira Paulo C. G. , Vieira Sabrina B. , Sales Agust
Published: September 2020

This article addresses a case study on the application of criteria for harvesting, aiming at restoration and profitability in a degraded tropical forest in the Amazon. The objective is to provide technical and economic information to promote a truly sustainable silvicultural management system in forests with this profile and turn them into a desirable financial asset for conservation and social development. In the forest census, 85.907 trees ha−1 (100.8566 m3 ha−1) were inventoried with diameter at breast height (dbh) ≥ 25 cm, belonging to 106 commercial species. When applying the harvest criteria, 19.923 trees ha−1 (29.99 m3 ha−1), referring to 53 species, were destined for harvest. Some trees were selected by more than one criterion, totalizing 17.985 trees ha−1 by density, 1.831 trees ha−1 by compromised health, 0.212 trees ha−1 by maximum dbh, 18.933 trees ha−1 by minimum dbh, 1.385 trees ha−1 by tree stem (quality 3), and 0.080 trees ha−1 by species conservation. In all scenarios, the application of criteria for harvesting proved to be profitable with excellent cost–benefit ratios. The selection of trees with a minimum cutting diameter of 25 cm in shorter cycles tends to allow the promotion of new commercial species. The set of actions presented has the potential to favor the maintenance of biodiversity and expansion of low-density populations, health and the potential increment of the forest productivity. In addition, it is more feasible for the supply of forest products in a shorter time than provided for in Brazilian regulations; however, they must respect the specificities of the species and also of the site.
Image Quality and Interpretation of [18F]-FES-PET: Is There any Effect of Food Intake?
Authors: Boers Jorianne , Giatagana Katerina , Schröder Carolina P. , Hospers Geke A.P. , de Vries Erik F.J. , Glaudemans Andor W.J.M.
Published: September 2020

Background: High physiological 16α-[18F]-fluoro-17β-estradiol ([18F]-FES) uptake in the abdomen is a limitation of this positron emission tomography (PET) tracer. Therefore, we investigated the effect of food intake prior to PET acquisition on abdominal background activity in [18F]-FES-PET scans. Methods: Breast cancer patients referred for [18F]-FES-PET were included. Three groups were designed: (1) patients who consumed a chocolate bar (fatty meal) between tracer injection and imaging (n = 20), (2) patients who fasted before imaging (n = 20), and (3) patients without diet restrictions (control group, n = 20). We compared the physiological [18F]-FES uptake, expressed as mean standardized uptake value (SUVmean), in the abdomen between groups. Results: A significant difference in [18F]-FES uptake in the gall bladder and stomach lumen was observed between groups, with the lowest values for the chocolate group and highest for the fasting group (p = 0.015 and p = 0.011, respectively). Post hoc analysis showed significant differences in the SUVmean of these organs between the chocolate and fasting groups, but not between the chocolate and control groups. Conclusion: This exploratory study showed that, compared to fasting, eating chocolate decreases physiological gall bladder and stomach [18F]-FES uptake; further reduction through a normal diet was not seen. A prospective study is warranted to confirm this finding.