bluuebunny/crossref_metadata_2025 huggingface dataset:
Machaerium hirtum (Vell.) Stellfeld Alleviates Acute Pain and Inflammation: Potential Mechanisms of Action
Authors: Lopes Juliana Agostinho , Rodrigues Vinícius Peixoto , Tangerina Marcelo Marucci Pereira , Rocha Lucia Regina Machado da , Nishijima Catarine Massucato , Nunes Vania Vasti Alfieri , de Almeida Luiz Fernando Rolim , Vilegas Wagner , dos Santos Adair Roberto Soares , Sannomiya Miriam , Hiruma-Lima Clélia Akiko
Published: April 2020

Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as “jacaranda de espinho” or “espinheira santa nativa” is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, l-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE2) showed involvement of the COX pathway, based on observed decreases in PGE2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, β-amyrin, allantoin, apigenin-7-methoxy-6-C-β-d-glucopyranoside, and apigenin-6-C-β-d-glucopyranosyl-8-C-β-d-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE2 levels.
Y-Box Binding Proteins in mRNP Assembly, Translation, and Stability Control
Authors: Mordovkina Daria , Lyabin Dmitry N. , Smolin Egor A. , Sogorina Ekaterina M. , Ovchinnikov Lev P. , Eliseeva Irina
Published: April 2020

Y-box binding proteins (YB proteins) are DNA/RNA-binding proteins belonging to a large family of proteins with the cold shock domain. Functionally, these proteins are known to be the most diverse, although the literature hardly offers any molecular mechanisms governing their activities in the cell, tissue, or the whole organism. This review describes the involvement of YB proteins in RNA-dependent processes, such as mRNA packaging into mRNPs, mRNA translation, and mRNA stabilization. In addition, recent data on the structural peculiarities of YB proteins underlying their interactions with nucleic acids are discussed.
Gamma-Aminobutyric Acid Increases Erythropoietin by Activation of Citrate Cycle and Stimulation of Hypoxia-Inducible Factors Expression in Rats
Authors: Park Keun-Tae , Han Jong-Kwon , Kim Seong Jin , Lim Young-Hee
Published: April 2020

Erythropoietin (EPO) is the primary regulator of erythropoiesis in the mammalian fetus and adult. Deficiency of EPO induces anemia. In this study, we investigated the effect of gamma-aminobutyric acid (GABA) on serum EPO levels and erythropoiesis in rats. Expression levels of Epo-related genes were measured by quantitative real-time PCR (qPCR) and expression of Epo and Epo receptor (Epor) proteins were measured by immunohistochemistry. The gene and protein expression profiles of kidney tissue in GABA-treated rats were evaluated by ribonucleic acid (RNA) sequencing and two-dimensional electrophoresis (2-DE), respectively. GABA significantly increased serum EPO levels and expression levels of Epo and Epor. GABA increased expression levels of hypoxia-inducible factor (Hif)-1 and Hif-2. Seven proteins with expression levels showing >2-fold change were identified by 2-DE followed by MALDI-TOF MS in GABA-treated rat kidney. The top KEGG pathway from the identified proteins was the tricarboxylic acid cycle, and nicotinamide adenine dinucleotide (NADH) dehydrogenase, succinate dehydrogenase, and isocitrate dehydrogenase were identified as key proteins. GABA treatment significantly increased ATP levels and NADH dehydrogenase activity in a dose-dependent manner. In conclusion, GABA shows a new physiological role in EPO production, and it can thus can contribute to the prevention of anemia when used alone or in combination with other anemia treating drugs.
The ADAMTS/Fibrillin Connection: Insights into the Biological Functions of ADAMTS10 and ADAMTS17 and Their Respective Sister Proteases
Authors: Karoulias Stylianos Z. , Taye Nandaraj , Stanley Sarah , Hubmacher Dirk
Published: April 2020

Secreted a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS) proteases play crucial roles in tissue development and homeostasis. The biological and pathological functions of ADAMTS proteases are determined broadly by their respective substrates and their interactions with proteins in the pericellular and extracellular matrix. For some ADAMTS proteases, substrates have been identified and substrate cleavage has been implicated in tissue development and in disease. For other ADAMTS proteases, substrates were discovered in vitro, but the role of these proteases and the consequences of substrate cleavage in vivo remains to be established. Mutations in ADAMTS10 and ADAMTS17 cause Weill–Marchesani syndrome (WMS), a congenital syndromic disorder that affects the musculoskeletal system (short stature, pseudomuscular build, tight skin), the eyes (lens dislocation), and the heart (heart valve abnormalities). WMS can also be caused by mutations in fibrillin-1 (FBN1), which suggests that ADAMTS10 and ADAMTS17 cooperate with fibrillin-1 in a common biological pathway during tissue development and homeostasis. Here, we compare and contrast the biochemical properties of ADAMTS10 and ADAMTS17 and we summarize recent findings indicating potential biological functions in connection with fibrillin microfibrils. We also compare ADAMTS10 and ADAMTS17 with their respective sister proteases, ADAMTS6 and ADAMTS19; both were recently linked to human disorders distinct from WMS. Finally, we propose a model for the interactions and roles of these four ADAMTS proteases in the extracellular matrix.
High-Density Lipoproteins Are Bug Scavengers
Authors: Meilhac Olivier , Tanaka Sébastien , Couret David
Published: April 2020

Lipoproteins were initially defined according to their composition (lipids and proteins) and classified according to their density (from very low- to high-density lipoproteins—HDLs). Whereas their capacity to transport hydrophobic lipids in a hydrophilic environment (plasma) is not questionable, their primitive function of cholesterol transporter could be challenged. All lipoproteins are reported to bind and potentially neutralize bacterial lipopolysaccharides (LPS); this is particularly true for HDL particles. In addition, HDL levels are drastically decreased under infectious conditions such as sepsis, suggesting a potential role in the clearance of bacterial material and, particularly, LPS. Moreover, "omics" technologies have unveiled significant changes in HDL composition in different inflammatory states, ranging from acute inflammation occurring during septic shock to low-grade inflammation associated with moderate endotoxemia such as periodontal disease or obesity. In this review, we will discuss HDL modifications associated with exposure to pathogens including bacteria, viruses and parasites, with a special focus on sepsis and the potential of HDL therapy in this context. Low-grade inflammation associated with atherosclerosis, periodontitis or metabolic syndrome may also highlight the protective role of HDLs in theses pathologies by other mechanisms than the reverse transport of cholesterol.
Tussilagone Reduces Tumorigenesis by Diminishing Inflammation in Experimental Colitis-Associated Colon Cancer
Authors: Nam Sang-Hyeon , Kim Jin-Kyung
Published: April 2020

Background: Tussilagone, a major component of Tussilago farfara L., has anti-angiogenic and anti-inflammatory effects. However, the therapeutic and preventive activity of tussilagone in colitis-associated colon carcinogenesis is unknown. Methods: We intended to investigate the therapeutic effects and the potential mechanism of action underlying the pharmacological activity of tussilagone on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). We injected BALB/c mice with AOM and administered 2% DSS in drinking water. The mice were given tussilagone (2.5 and 5 mg/kg body weight) and colon tissues was collected at 72 days. We used Western blotting, immunohistochemistry and real-time RT-PCR analyses to examine the tumorigenesis and inflammatory status of the colon. Results: Tussilagone administration significantly reduced the formation of colonic tumors. In addition, tussilagone treatment markedly reduced the inflammatory mediators and increased heme oxygease-1 in protein and mRNA levels in colon tissues. Meanwhile, nuclear NF-κB-positive cells were elevated and nuclear Nrf2-positive cells were demised by tussilagone treatment in colon tissues. Tussilagone also reduced cell proliferation, induced apoptosis and decreased the β-catenin expression. Conclusions: Tussilagone administration decreases the inflammation and proliferation induced by AOM/DSS and induced apoptosis in colon tissue. Overall, this study indicates the potential value of tussilagone in suppressing colon tumorigenesis.
Integrated Electrochemical Biosensors for Detection of Waterborne Pathogens in Low-Resource Settings
Authors: Rainbow Joshua , Sedlackova Eliska , Jiang Shu , Maxted Grace , Moschou Despina , Richtera Lukas , Estrela Pedro
Published: April 2020

More than 783 million people worldwide are currently without access to clean and safe water. Approximately 1 in 5 cases of mortality due to waterborne diseases involve children, and over 1.5 million cases of waterborne disease occur every year. In the developing world, this makes waterborne diseases the second highest cause of mortality. Such cases of waterborne disease are thought to be caused by poor sanitation, water infrastructure, public knowledge, and lack of suitable water monitoring systems. Conventional laboratory-based techniques are inadequate for effective on-site water quality monitoring purposes. This is due to their need for excessive equipment, operational complexity, lack of affordability, and long sample collection to data analysis times. In this review, we discuss the conventional techniques used in modern-day water quality testing. We discuss the future challenges of water quality testing in the developing world and how conventional techniques fall short of these challenges. Finally, we discuss the development of electrochemical biosensors and current research on the integration of these devices with microfluidic components to develop truly integrated, portable, simple to use and cost-effective devices for use by local environmental agencies, NGOs, and local communities in low-resource settings.
Does Insomnia Exist without Hyperarousal? What Else Can There Be?
Authors: Bastien Célyne
Published: April 2020

While in ancient Greece, incubation rooms were dedicated to the interpretation of dreams, sleep was also studied by famous philosophers such as Aristotle [...]
Optimal Interplay between Synaptic Strengths and Network Structure Enhances Activity Fluctuations and Information Propagation in Hierarchical Modular Networks
Authors: Pena Rodrigo F. O. , Lima Vinicius , O. Shimoura Renan , Paulo Novato João , Roque Antonio C.
Published: April 2020

In network models of spiking neurons, the joint impact of network structure and synaptic parameters on activity propagation is still an open problem. Here, we use an information-theoretical approach to investigate activity propagation in spiking networks with a hierarchical modular topology. We observe that optimized pairwise information propagation emerges due to the increase of either (i) the global synaptic strength parameter or (ii) the number of modules in the network, while the network size remains constant. At the population level, information propagation of activity among adjacent modules is enhanced as the number of modules increases until a maximum value is reached and then decreases, showing that there is an optimal interplay between synaptic strength and modularity for population information flow. This is in contrast to information propagation evaluated among pairs of neurons, which attains maximum value at the maximum values of these two parameter ranges. By examining the network behavior under the increase of synaptic strength and the number of modules, we find that these increases are associated with two different effects: (i) the increase of autocorrelations among individual neurons and (ii) the increase of cross-correlations among pairs of neurons. The second effect is associated with better information propagation in the network. Our results suggest roles that link topological features and synaptic strength levels to the transmission of information in cortical networks.
Diffuse Axonal Injury in the Rat Brain: Axonal Injury and Oligodendrocyte Activity Following Rotational Injury
Authors: Losurdo Michela , Davidsson Johan , Sköld Mattias K.
Published: April 2020

Traumatic brain injury (TBI) commonly results in primary diffuse axonal injury (DAI) and associated secondary injuries that evolve through a cascade of pathological mechanisms. We aim at assessing how myelin and oligodendrocytes react to head angular-acceleration-induced TBI in a previously described model. This model induces axonal injuries visible by amyloid precursor protein (APP) expression, predominantly in the corpus callosum and its borders. Brain tissue from a total of 27 adult rats was collected at 24 h, 72 h and 7 d post-injury. Coronal sections were prepared for immunohistochemistry and RNAscope® to investigate DAI and myelin changes (APP, MBP, Rip), oligodendrocyte lineage cell loss (Olig2), oligodendrocyte progenitor cells (OPCs) (NG2, PDGFRa) and neuronal stress (HSP70, ATF3). Oligodendrocytes and OPCs numbers (expressed as percentage of positive cells out of total number of cells) were measured in areas with high APP expression. Results showed non-statistically significant trends with a decrease in oligodendrocyte lineage cells and an increase in OPCs. Levels of myelination were mostly unaltered, although Rip expression differed significantly between sham and injured animals in the frontal brain. Neuronal stress markers were induced at the dorsal cortex and habenular nuclei. We conclude that rotational injury induces DAI and neuronal stress in specific areas. We noticed indications of oligodendrocyte death and regeneration without statistically significant changes at the timepoints measured, despite indications of axonal injuries and neuronal stress. This might suggest that oligodendrocytes are robust enough to withstand this kind of trauma, knowledge important for the understanding of thresholds for cell injury and post-traumatic recovery potential.
How Children with Autism Spectrum Disorder, Developmental Language Disorder, and Typical Language Learn to Produce Global and Local Semantic Features
Authors: Gladfelter Allison , Barron Kacy L.
Published: April 2020

A local processing bias, often considered a cognitive style unique to autism spectrum disorder (ASD), may influence the types of semantic features acquired by children with ASD and could contribute to weaknesses in word learning. Children with developmental language disorder (DLD) also struggle to learn semantic aspects of words, but this cognitive style has not been ascribed to children with DLD. The purpose of this study was to explore whether global–local processing differences influence the type of semantic features children with ASD, DLD, and their neurotypical peers learn to produce when learning new words. Novel word definitions produced by 36 school-aged children (12 with ASD, 12 with DLD, and 12 with typical language) who participated in an extended word-learning paradigm were used to extract newly learned semantic features. These semantic features were then coded for global and local attributes and analyzed to detect whether there were differences between groups. Results indicated that the children with ASD and DLD produced more global, rather than local, semantic features in their definitions than the children with typical language. An over-reliance on global, rather than local, features in children with ASD and DLD may reflect deficits in depth of word knowledge.
Review on Activated Carbons by Chemical Activation with FeCl3
Authors: Bedia Jorge , Peñas-Garzón Manuel , Gómez-Avilés Almudena , Rodriguez Juan J. , Belver Carolina
Published: April 2020

This study reviews the most relevant results on the synthesis, characterization, and applications of activated carbons obtained by novel chemical activation with FeCl3. The text includes a description of the activation mechanism, which compromises three different stages: (1) intense de-polymerization of the carbon precursor (up to 300 °C), (2) devolatilization and formation of the inner porosity (between 300 and 700 °C), and (3) dehydrogenation of the fixed carbon structure (>700 °C). Among the different synthesis conditions, the activation temperature, and, to a lesser extent, the impregnation ratio (i.e., mass ratio of FeCl3 to carbon precursor), are the most relevant parameters controlling the final properties of the resulting activated carbons. The characteristics of the carbons in terms of porosity, surface chemistry, and magnetic properties are analyzed in detail. These carbons showed a well-developed porous texture mainly in the micropore size range, an acidic surface with an abundance of oxygen surface groups, and a superparamagnetic character due to the presence of well-distributed iron species. These properties convert these carbons into promising candidates for different applications. They are widely analyzed as adsorbents in aqueous phase applications due to their porosity, surface acidity, and ease of separation. The presence of stable and well-distributed iron species on the carbons’ surface makes them promising catalysts for different applications. Finally, the presence of iron compounds has been shown to improve the graphitization degree and conductivity of the carbons; these are consequently being analyzed in energy storage applications.
Future Challenges in Cancer Resistance to Immunotherapy
Authors: van Elsas Marit J. , van Hall Thorbald , van der Burg Sjoerd H.
Published: April 2020

Cancer immunotherapies, including checkpoint inhibitors, adoptive T cell transfer and therapeutic cancer vaccines, have shown promising response rates in clinical trials. Unfortunately, there is an increasing number of patients in which initially regressing tumors start to regrow due to an immunotherapy-driven acquired resistance. Studies on the underlying mechanisms reveal that these can be similar to well-known tumor intrinsic and extrinsic primary resistance factors that precluded the majority of patients from responding to immunotherapy in the first place. Here, we discuss primary and secondary immune resistance and point at strategies to identify potential new mechanisms of immune evasion. Ultimately, this may lead to improved immunotherapy strategies with improved clinical outcomes.
Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments
Authors: Rajaratnam Vilashini , Islam Mohammad , Yang Maixee , Slaby Rachel , Ramirez Hilda , Mirza Shama
Published: April 2020

Glioblastoma is one of the most common and detrimental forms of solid brain tumor, with over 10,000 new cases reported every year in the United States. Despite aggressive multimodal treatment approaches, the overall survival period is reported to be less than 15 months after diagnosis. A widely used approach for the treatment of glioblastoma is surgical removal of the tumor, followed by radiotherapy and chemotherapy. While there are several drugs available that are approved by the Food and Drug Administration (FDA), significant efforts have been made in recent years to develop new chemotherapeutic agents for the treatment of glioblastoma. This review describes the molecular targets and pathogenesis as well as the current progress in chemotherapeutic development and other novel therapies in the clinical setting for the treatment of glioblastoma.
Efficacy of the EDP-M Scheme Plus Adjunctive Surgery in the Management of Patients with Advanced Adrenocortical Carcinoma: The Brescia Experience
Authors: Laganà Marta , Grisanti Salvatore , Cosentini Deborah , Ferrari Vittorio Domenico , Lazzari Barbara , Ambrosini Roberta , Sardini Chiara , Dalla Volta Alberto , Palumbo Carlotta , Poliani Pietro Luigi , Terzolo Massimo , Sigala Sandra , Tiberio Guido Alberto Massimo , Berruti Alfredo
Published: April 2020

Etoposide, doxorubicin and cisplatin plus oral mitotane (EDP-M) comprise the reference regimen in the management of patients with adrenocortical carcinoma (ACC). In this paper, we described the outcome of 58 patients with advanced/metastatic ACC consecutively treated with EDP-M in a reference center for this rare disease in Italy. In this series, EDP-M obtained a partial response in 50% of patients; median progression free survival (PFS) and overall survival were 10.1 months (95% Confidence Interval [CI 95%] 8.1–12.8) and 18.7 months (95% CI: 14.6–22.8), respectively. EDP-M was not interrupted in five patients showing disease progression after two cycles without the appearance of new lesions and mitotane levels below the therapeutic range. In two of them, the disease remained stable at further imaging evaluations and the other three obtained a partial response. Twenty-six responding patients underwent surgery of residual disease and 13 of them became disease free. Surgery identified a pathological complete response (pCR) in four patients (7%) and Ki67 expression in post-chemotherapy tumor specimens, inferior to 15% (median value), was associated with better PFS and survival. In the present study, the EDP-M regimen is confirmed to have a limited efficacy. Early disease progression does not mean treatment inefficacy. Surgery of residual disease in partially responding patients allows for the detection of pCR in few of them and this condition is predictive of long-term survival. Ki67 expression of post-chemotherapy residual disease could be an additional prognostic factor that deserves to be studied further.
Genomic Profiling of Circulating Tumor DNA Predicts Outcome and Demonstrates Tumor Evolution in ALK-Positive Non-Small Cell Lung Cancer Patients
Authors: Madsen Anne Tranberg , Winther-Larsen Anne , McCulloch Tine , Meldgaard Peter , Sorensen Boe Sandahl
Published: April 2020

With the rapid development of targeted therapies for the treatment of cancer, methods for predicting response and outcome are in high demand. Non-small cell lung cancer driven by genomic rearrangements of the anaplastic lymphoma kinase (ALK) gene can be successfully treated with ALK-targeted therapy. Unfortunately, a subset of patients does not respond, and all patients ultimately acquire resistance, highlighting the need for better clinical tools to manage these patients. Here, we performed targeted next-generation sequencing on plasma circulating tumor DNA (ctDNA) from 24 patients to assess the clinical utility of ctDNA genomic profiling. Patients with detectable ctDNA prior to treatment had worse progression-free survival (PFS) than those without (median 8.7 vs. 15.2 months, p = 0.028). In addition, the presence of ctDNA within two months after treatment initiation predicted inferior PFS (median 4.6 vs. 14.5 months, p = 0.028). Longitudinal monitoring of ctDNA with droplet digital PCR during treatment reflected the radiological response and revealed potential acquired resistance mutations. Interestingly, an increase in the ctDNA concentration was evident prior to the determination of progressive disease by conventional radiological imaging, with a median lead time of 69 days (range 30–113). Genomic profiling of ctDNA is a promising tool for predicting outcome and monitoring response to targeted therapy.
EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways
Authors: Farooqi Ammad Ahmad , Pinheiro Marina , Granja Andreia , Farabegoli Fulvia , Reis Salette , Attar Rukset , Sabitaliyevich Uteuliyev Yerzhan , Xu Baojun , Ahmad Aamir
Published: April 2020

Decades of research have enabled us to develop a better and sharper understanding of multifaceted nature of cancer. Next-generation sequencing technologies have leveraged our existing knowledge related to intra- and inter-tumor heterogeneity to the next level. Functional genomics have opened new horizons to explore deregulated signaling pathways in different cancers. Therapeutic targeting of deregulated oncogenic signaling cascades by products obtained from natural sources has shown promising results. Epigallocatechin-3-gallate (EGCG) has emerged as a distinguished chemopreventive product because of its ability to regulate a myriad of oncogenic signaling pathways. Based on its scientifically approved anticancer activity and encouraging results obtained from preclinical trials, it is also being tested in various phases of clinical trials. A series of clinical trials associated with green tea extracts and EGCG are providing clues about significant potential of EGCG to mechanistically modulate wide ranging signal transduction cascades. In this review, we comprehensively analyzed regulation of JAK/STAT, Wnt/β-catenin, TGF/SMAD, SHH/GLI, NOTCH pathways by EGCG. We also discussed most recent evidence related to the ability of EGCG to modulate non-coding RNAs in different cancers. Methylation of the genome is also a widely studied mechanism and EGCG has been shown to modulate DNA methyltransferases (DNMTs) and protein enhancer of zeste-2 (EZH2) in multiple cancers. Moreover, the use of nanoformulations to increase the bioavailability and thus efficacy of EGCG will be also addressed. Better understanding of the pleiotropic abilities of EGCG to modulate intracellular pathways along with the development of effective EGCG delivery vehicles will be helpful in getting a step closer to individualized medicines.
High Galectin-7 and Low Galectin-8 Expression and the Combination of both are Negative Prognosticators for Breast Cancer Patients
Authors: Trebo Anna , Ditsch Nina , Kuhn Christina , Heidegger Helene Hildegard , Zeder-Goess Christine , Kolben Thomas , Czogalla Bastian , Schmoeckel Elisa , Mahner Sven , Jeschke Udo , Hester Anna
Published: April 2020

Galectins are commonly overexpressed in cancer cells and their expression pattern is often associated with the aggressiveness and metastatic phenotype of the tumor. This study investigates the prognostic influence of the expression of galectin-7 (Gal-7) and galectin-8 (Gal-8) in tumor cell cytoplasm, nucleus and on surrounding immune cells. Primary breast cancer tissue of 235 patients was analyzed for the expression of Gal-7 and Gal-8 and correlated with clinical and pathological data and the outcome. To identify immune cell subpopulations, immunofluorescence double staining was performed. Significant correlations of Gal-7 expression in the cytoplasm with HER2-status, PR status, patient age and grading, and of Gal-8 expression in the cytoplasm with HER2-status and patient age and of both galectins between each other were found. A high Gal-7 expression in the cytoplasm was a significant independent prognosticator for an impaired progression free survival (PFS) (p = 0.017) and distant disease-free survival (DDFS) (p = 0.030). Gal-7 was also expressed by tumor-infiltrating macrophages. High Gal-8 expression in the cytoplasm was associated with a significantly improved overall survival (OS) (p = 0.032). Clinical outcome in patients showing both high Gal-7 and with low Gal-8 expression was very poor. Further understanding of the role of galectins in the regulation and interaction of tumor cells and macrophages is essential for finding new therapeutic targets.
Enhancement of Photocatalytic Oxidation of Glucose to Value-Added Chemicals on TiO2 Photocatalysts by A Zeolite (Type Y) Support and Metal Loading
Authors: Roongraung Kamonchanok , Chuangchote Surawut , Laosiripojana Navadol
Published: April 2020

TiO2-based photocatalysts synthesized by the microwave-assisted sol-gel method was tested in the photocatalytic glucose conversion. Modifications of TiO2 with type-Y zeolite (ZeY) and metals (Ag, Cu, and Ag-Cu) were developed for increasing the dispersion of TiO2 nanoparticles and increasing the photocatalytic activity. Effects of the TiO2 dosage to zeolite ratio (i.e., TiO2/ZeY of 10, 20, 40, and 50 mol %) and the silica to alumina ratio in ZeY (i.e., SiO2:Al2O3 of 10, 100, and 500) were firstly studied. It was found that the specific surface area of TiO2/ZeY was 400–590 m2g−1, which was higher than that of pristine TiO2 (34.38 m2g−1). The good properties of 20%TiO2/ZeY photocatalyst, including smaller particles (13.27 nm) and high surface area, could achieve the highest photocatalytic glucose conversion (75%). Yields of gluconic acid, arabinose, xylitol, and formic acid obtained from 20%TiO2/ZeY were 9%, 26%, 4%, and 35%, respectively. For the effect of the silica to alumina ratio, the highest glucose conversion was obtained from SiO2:Al2O3 ratio of 100. Interestingly, it was found that the SiO2:Al2O3 ratio affected the selectivity of carboxylic products (gluconic acid and formic acid). At a low ratio of silica to alumina (SiO2:Al2O3 = 10), higher selectivity of the carboxylic products (gluconic acid = 29% and formic acid = 32%) was obtained (compared with other higher ratios). TiO2/ZeY was further loaded by metals using the microwave-assisted incipient wetness impregnation technique. The highest glucose conversion of 96.9 % was obtained from 1 wt. % Ag-TiO2 (40%)/ZeY. Furthermore, the bimetallic Ag-Cu-loaded TiO2/ZeY presented the highest xylitol yield of 12.93%.
Inflammatory Conditions Disrupt Constitutive Endothelial Cell Barrier Stabilization by Alleviating Autonomous Secretion of Sphingosine 1-Phosphate
Authors: Jeya Paul Jefri , Weigel Cynthia , Müller Tina , Heller Regine , Spiegel Sarah , Gräler Markus H.
Published: April 2020

The breakdown of the endothelial cell (EC) barrier contributes significantly to sepsis mortality. Sphingosine 1-phosphate (S1P) is one of the most effective EC barrier-stabilizing signaling molecules. Stabilization is mainly transduced via the S1P receptor type 1 (S1PR1). Here, we demonstrate that S1P was autonomously produced by ECs. S1P secretion was significantly higher in primary human umbilical vein endothelial cells (HUVEC) compared to the endothelial cell line EA.hy926. Constitutive barrier stability of HUVEC, but not EA.hy926, was significantly compromised by the S1PR1 antagonist W146 and by the anti-S1P antibody Sphingomab. HUVEC and EA.hy926 differed in the expression of the S1P-transporter Spns2, which allowed HUVEC, but not EA.hy926, to secrete S1P into the extracellular space. Spns2 deficient mice showed increased serum albumin leakage in bronchoalveolar lavage fluid (BALF). Lung ECs isolated from Spns2 deficient mice revealed increased leakage of fluorescein isothiocyanate (FITC) labeled dextran and decreased resistance in electric cell-substrate impedance sensing (ECIS) measurements. Spns2 was down-regulated in HUVEC after stimulation with pro-inflammatory cytokines and lipopolysaccharides (LPS), which contributed to destabilization of the EC barrier. Our work suggests a new mechanism for barrier integrity maintenance. Secretion of S1P by EC via Spns2 contributed to constitutive EC barrier maintenance, which was disrupted under inflammatory conditions via the down-regulation of the S1P-transporter Spns2.
Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent
Authors: Scagliarini Alessandra , Mathey Aline , Aires Virginie , Delmas Dominique
Published: April 2020

In spite of chemotherapy and systematic screening for people at risk, the mortality rate of colorectal cancer (CRC) remains consistently high, with 600,000 deaths per year. This low success rate in the treatment of CRC results from many failures associated with high resistance and the risk of metastasis. Therefore, in response to these therapeutic failures, new strategies have been under development for several years aimed at increasing the effect of anticancer compounds and/or at reducing their secondary effects on normal cells, thus enabling the host to better withstand chemotherapy. This study highlights that xanthohumol (Xn) concentrations under the IC50 values were able to induce apoptosis and to enhance the DNA-damage response (DDR). We demonstrate for the first time that Xn exerts its anticancer activity in models of colon cancer through activation of the ataxia telangiectasia mutated (ATM) pathway. Subsequently, the ability of Xn to restore DNA damage in CRC cells can sensitize them to anticancer agents such as SN38 (7-ethyl-10-hydroxycamptothecin) used in chemotherapy.
hnRNP A1 Regulates Alternative Splicing of Tau Exon 10 by Targeting 3′ Splice Sites
Authors: Liu Yongchao , Kim Donggun , Choi Namjeong , Oh Jagyeong , Ha Jiyeon , Zhou Jianhua , Zheng Xuexiu , Shen Haihong
Published: April 2020

The ratio control of 4R-Tau/3R-Tau by alternative splicing of Tau exon 10 is important for maintaining brain functions. In this study, we show that hnRNP A1 knockdown induces inclusion of endogenous Tau exon 10, conversely, overexpression of hnRNP A1 promotes exon 10 skipping of Tau. In addition, hnRNP A1 inhibits splicing of intron 9, but not intron 10. Furthermore, hnRNP A1 directly interacts with the 3′ splice site of exon 10 to regulate its functions in alternative splicing. Finally, gene ontology analysis demonstrates that hnRNP A1-induced splicing and gene expression targets a subset of genes with neuronal function.
Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade
Authors: Rossi Alessandra , Lucarini Valeria , Macchia Iole , Sestili Paola , Buccione Carla , Donati Simona , Ciccolella Maria , Sistigu Antonella , D’Urso Maria Teresa , Pacca Anna Maria , Cardarelli Enrico , Mattei Fabrizio , Proietti Enrico , Schiavoni Giovanna , Bracci Laura
Published: April 2020

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment providing unprecedented clinical benefits. However, many patients do not respond to ICIs as monotherapy or develop resistance. Combining ICI-based immunotherapy with chemotherapy is a promising strategy to increase response rates, but few rationale-driven chemo-immunotherapy combinations have reached the clinical arena thus far. In the present study, we show that combined anti-PDL1 and anti-PDL2 antibodies optimally synergize with cyclophosphamide but not with cisplatin, and that the magnitude and duration of the therapeutic response is dependent on the immunogenic potential of the drug and of the tumor itself. Hallmarks of successful therapeutic outcomes were the enhanced infiltration by myeloid (mainly cross-presenting dendritic cells, eosinophils, and monocytic myeloid cells) and T lymphocytes into the tumor tissue and the expansion of circulating memory pools. Overall, our results suggest that immunomodulating chemotherapy can be exploited to increase the efficacy of PD1/PDL axis inhibitors in vivo, and that the magnitude of the synergic therapeutic response is affected by tumor-intrinsic immunogenicity.
Integration of Microalgae Cultivation in a Biogas Production Process from Organic Municipal Solid Waste: From Laboratory to Pilot Scale
Authors: Barreiro-Vescovo Santiago , Barbera Elena , Bertucco Alberto , Sforza Eleonora
Published: April 2020

In this study, the feasibility of integrating microalgae cultivation in a biogas production process that treats the organic fraction of municipal solid waste (OFMSW) was investigated. In particular, the biomass growth performances in the liquid fraction of the digestate, characterized by high ammonia concentrations and turbidity, were assessed together with the nutrient removal efficiency. Preliminary laboratory-scale experiments were first carried out in photobioreactors operating in a continuous mode (Continuous-flow Stirred-Tank Reactor, CSTR), to gain preliminary data aimed at aiding the subsequent scaling up to a pilot scale facility. An outdoor experimental campaign, operated from July to October 2019, was then performed in a pilot scale raceway pond (4.5 m2), located in Arzignano (VI), Italy, to assess the performances under real environmental conditions. The results show that microalgae could grow well in this complex substrate, although dilution was necessary to enhance light penetration in the culture. In outdoor conditions, nitrification by autotrophic bacteria appeared to be significant, while the photosynthetic nitrogen removal was around 12% with respect to the inlet. On the other hand, phosphorus was almost completely removed from the medium under all the conditions tested, and a biomass production between 2–7 g m−2 d−1 was obtained.
The Author’s Contributions to Echocardiography Literature (Part I—1978–1990)
Authors: Rao P. Syamasundar
Published: April 2020

The author has undertaken multiple echocardiographic studies during his academic career; most of these were published in peer-reviewed journals. These studies include an evaluation of the role of echocardiography in the estimation of left-to-right shunt in isolated ventricular septal defects, an examination of the utility of contrast echocardiography in the diagnosis of anomalous connection of the right superior vena cava to the left atrium, a description of pitfalls in M-mode echocardiographic assessment of the aortic root in left ventricular hypoplasia syndromes, reviews of echocardiographic evaluation of left ventricular function, study of the role of contrast echocardiography in the evaluation of hypoxemia following open heart surgery, a quantification of left ventricular muscle mass by m-mode echocardiography in children, an examination of race and sex related differences in echocardiographic measurements in children, study of cardiac size and function in patients with sickle cell disease, an examination of afterload reduction in the management of primary myocardial disease, study of the utility of echo-Doppler studies in the evaluation of the results of balloon pulmonary valvuloplasty, study of the usefulness of Doppler in the prediction of pressure gradients in valvar pulmonary stenosis, a review of Doppler echocardiography in noninvasive diagnoses of heart disease, echo-Doppler studies of the evaluation of the results of balloon angioplasty of aortic coarctation, study of the value of Doppler in the prediction of pressure gradients across coarctation of the aorta, and a characterization of foramen ovale and transatrial Doppler velocity patterns in the normal fetus.
Analysis of Anomalies and Trends of Climate Change Indices in Zacatecas, Mexico
Authors: Pita-Díaz Oscar , Ortega-Gaucin David
Published: April 2020

Sufficient evidence is currently available to demonstrate the reality of the warming of our planet’s climate system. Global warming has different effects on climate at the regional and local levels. The detection of changes in extreme events using instrumental data provides further evidence of such warming and allows for the characterization of its local manifestations. The present study analyzes changes in temperature and precipitation extremes in the Mexican state of Zacatecas using climate change indices developed by the Expert Team on Climate Change Detection and Indices (ETCCDI). We studied a 40-year period (1976–2015) using annual and seasonal time series. Maximum and minimum temperature data were used, as well as precipitation statistics from the Mexican climatology database (CLICOM) provided by the Mexican Meteorological Service. Weather stations with at least 80% of data availability for the selected study period were selected; these databases were subjected to quality control, homogenization, and data filling using Climatol, which runs in the R programming language. These homogenized series were used to obtain daily grids of the three variables at a resolution of 1.3 km. Results reveal important changes in temperature-related indices, such as the increase in maximum temperature and the decrease in minimum temperature. Irregular variability was observed in the case of precipitation, which could be associated with low-frequency oscillations such as the Pacific Decadal Oscillation and the El Niño–Southern Oscillation. The possible impact of these changes in temperature and the increased irregularity of precipitation could have a negative impact on the agricultural sector, especially given that the state of Zacatecas is the largest national bean producer. The most important problems in the short term will be related to the difficulty of adapting to these rapid changes and the new climate scenario, which will pose new challenges in the future.
Gas Transport in Mixed Matrix Membranes: Two Methods for Time Lag Determination
Authors: Fuoco Alessio , Monteleone Marcello , Esposito Elisa , Bruno Rosaria , Ferrando-Soria Jesús , Pardo Emilio , Armentano Donatella , Jansen Johannes Carolus
Published: April 2020

The most widely used method to measure the transport properties of dense polymeric membranes is the time lag method in a constant volume/pressure increase instrument. Although simple and quick, this method provides only relatively superficial, averaged data of the permeability, diffusivity, and solubility of gas or vapor species in the membrane. The present manuscript discusses a more sophisticated computational method to determine the transport properties on the basis of a fit of the entire permeation curve, including the transient period. The traditional tangent method and the fitting procedure were compared for the transport of six light gases (H2, He, O2, N2, CH4, and CO2) and ethane and ethylene in mixed matrix membranes (MMM) based on Pebax®1657 and the metal–organic framework (MOF) CuII2(S,S)-hismox·5H2O. Deviations of the experimental data from the theoretical curve could be attributed to the particular MOF structure, with cavities of different sizes. The fitting procedure revealed two different effective diffusion coefficients for the same gas in the case of methane and ethylene, due to the unusual void morphology in the MOFs. The method was furthermore applied to mixed gas permeation in an innovative constant-pressure/variable-volume setup with continuous analysis of the permeate composition by an on-line mass-spectrometric residual gas analyzer. This method can provide the diffusion coefficient of individual gas species in a mixture, during mixed gas permeation experiments. Such information was previously inaccessible, and it will greatly enhance insight into the mixed gas transport in polymeric or mixed matrix membranes.
Nanostructured TiC Layer is Highly Suitable Surface for Adhesion, Proliferation and Spreading of Cells
Authors: Lopreiato Mariangela , Mariano Alessia , Cocchiola Rossana , Longo Giovanni , Dalla Vedova Pietro , Scandurra Roberto , Scotto d’Abusco Anna
Published: April 2020

Cell culture is usually performed in 2D polymer surfaces; however, several studies are conducted with the aim to screen functional coating molecules to find substrates more suitable for cell adhesion and proliferation. The aim of this manuscript is to compare the cell adhesion and cytoskeleton organization of different cell types on different surfaces. Human primary fibroblasts, chondrocytes and osteoblasts isolated from patients undergoing surgery were seeded on polystyrene, poly-d-lysine-coated glass and titanium carbide slides and left to grow for several days. Then their cytoskeleton was analyzed, both by staining cells with phalloidin, which highlights actin fibers, and using Atomic Force Microscopy. We also monitored the production of Fibroblast Growth Factor-2, Bone Morphogenetic Protein-2 and Osteocalcin, using ELISA, and we highlighted production of Collagen type I in fibroblasts and osteoblasts and Collagen type II in chondrocytes by immunofluorescences. Fibroblasts, chondrocytes and osteoblasts showed both an improved proliferative activity and a good adhesion ability when cultured on titanium carbide slides, compared to polystyrene and poly-d-lysine-coated glass. In conclusion, we propose titanium carbide as a suitable surface to cultivate cells such as fibroblasts, chondrocytes and osteoblasts, allowing the preservation of their differentiated state and good adhesion properties.
Treatment of Head Louse Infestation with a Novel Mixture Made of Semi-Crystalline Polymers and Plant Extracts: Blind, Randomized, Controlled, Superiority Trial
Authors: Leal Cardoso José Henrique , Noronha Coelho de Souza Andrelina , Militão de Souza Francisco , Sa Preire Samia , Pinçon Claire
Published: April 2020

The rate of head louse infestations is increasing. Most of the neurotoxic treatments are not reliably ovicidal and are faced with genetic resistance. The treatments based on a mechanical mode of action show no sufficient efficacy, transferring the chances of a cure on a tedious combing or leaving the hair fatty. This double-blinded, randomized, controlled, superiority trial evaluates the efficacy and safety of a novel mixture made of semi-crystalline polymers and plant extracts. Forty-five participants received a single application of either 1% Permethrin lotion or the novel lotion, applied for 15 minutes. Untreated and treated nits were collected and placed in an incubator during 10 days. The worst case intent-to-treat analysis found the novel lotion significantly more effective than 1% Permethrin, with 21/22 (95.5%) participants cured and 9/23 (39.1%), respectively (p < 0.0001). Rate of viable nymphs was 0.5 (2.1) for the new lotion and 40.8 (20.4) for the 1% Permethrin. The new lotion cures head louse infestations, offering an effective alternative treatment, with a high efficacy for inhibiting the hatching of eggs. Its physical actions on lice and their eggs should not be affected by resistance to neurotoxic insecticides.
Side-Channel Power Resistance for Encryption Algorithms Using Implementation Diversity
Authors: Bow Ivan , Bete Nahome , Saqib Fareena , Che Wenjie , Patel Chintan , Robucci Ryan , Chan Calvin , Plusquellic Jim
Published: April 2020

This paper investigates countermeasures to side-channel attacks. A dynamic partial reconfiguration (DPR) method is proposed for field programmable gate arrays (FPGAs)s to make techniques such as differential power analysis (DPA) and correlation power analysis (CPA) difficult and ineffective. We call the technique side-channel power resistance for encryption algorithms using DPR, or SPREAD. SPREAD is designed to reduce cryptographic key related signal correlations in power supply transients by changing components of the hardware implementation on-the-fly using DPR. Replicated primitives within the advanced encryption standard (AES) algorithm, in particular, the substitution-box (SBOX)s, are synthesized to multiple and distinct gate-level implementations. The different implementations change the delay characteristics of the SBOXs, reducing correlations in the power traces, which, in turn, increases the difficulty of side-channel attacks. The effectiveness of the proposed countermeasures depends greatly on this principle; therefore, the focus of this paper is on the evaluation of implementation diversity techniques.