bluuebunny/crossref_metadata_2025 huggingface dataset:
Quercetin Potentiates Docosahexaenoic Acid to Suppress Lipopolysaccharide-induced Oxidative/Inflammatory Responses, Alter Lipid Peroxidation Products, and Enhance the Adaptive Stress Pathways in BV-2 Microglial Cells
Authors: Sun Grace Y. , Li Runting , Yang Bo , Fritsche Kevin L. , Beversdorf David Q. , Lubahn Dennis B. , Geng Xue , Lee James C. , Greenlief C. Michael
Published: February 2019

High levels of docosahexaenoic acid (DHA) in the phospholipids of mammalian brain have generated increasing interest in the search for its role in regulating brain functions. Recent studies have provided evidence for enhanced protective effects when DHA is administered in combination with phytochemicals, such as quercetin. DHA and quercetin can individually suppress lipopolysaccharide (LPS)–induced oxidative/inflammatory responses and enhance the antioxidative stress pathway involving nuclear factor erythroid-2 related factor 2 (Nrf2). However, studies with BV-2 microglial cells indicated rather high concentrations of DHA (IC50 in the range of 60–80 µM) were needed to produce protective effects. To determine whether quercetin combined with DHA can lower the levels of DHA needed to produce protective effects in these cells is the goal for this study. Results showed that low concentrations of quercetin (2.5 µM), in combination with DHA (10 µM), could more effectively enhance the expression of Nrf2 and heme oxygenase 1 (HO-1), and suppress LPS–induced nitric oxide, tumor necrosis factor-α, phospho-cytosolic phospholipase A2, reactive oxygen species, and 4-hydroxynonenal, as compared to the same levels of DHA or quercetin alone. These results provide evidence for the beneficial effects of quercetin in combination with DHA, and further suggest their potential as nutraceuticals for improving health.
Comparative Proteomic Analysis of Wheat Carrying Pm40 Response to Blumeria graminis f. sp. tritici Using Two-Dimensional Electrophoresis
Authors: Liang Yinping , Xia Ye , Chang Xiaoli , Gong Guoshu , Yang Jizhi , Hu Yuting , Cahill Madison , Luo Liya , Li Tao , He Lu , Zhang Min
Published: February 2019

Wheat powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) is considered a major wheat leaf disease in the main wheat producing regions of the world. Although many resistant wheat cultivars to this disease have been developed, little is known about their resistance mechanisms. Pm40 is a broad, effective resistance gene against powdery mildew in wheat line L699. The aim of this study was to investigate the resistance proteins after Bgt inoculation in wheat lines L699, Neimai836, and Chuannong26. Neimai836 with Pm21 was used as the resistant control, and Chuannong26 without any effective Pm genes was the susceptible control. Proteins were extracted from wheat leaves sampled 2, 4, 8, 12, and 24 h after Bgt inoculation, separated by two-dimensional electrophoresis, and stained with Coomassie brilliant blue G-250. The results showed that different proteins were upregulated and downregulated in three wheat cultivars at different time points. For the wheat cultivar L699, a total of 62 proteins were upregulated and 71 proteins were downregulated after Bgt inoculation. Among these, 46 upregulated proteins were identified by mass spectrometry analysis using the NCBI nr database of Triticum. The identified proteins were predicted to be associated with the defense response, photosynthesis, signal transduction, carbohydrate metabolism, energy pathway, protein turnover, and cell structure functions. It is inferred that the proteins are not only involved in defense response, but also other physiological and cellular processes to confer wheat resistance against Bgt. Therefore, the resistance products potentially mediate the immune response and coordinate other physiological and cellular processes during the resistance response to Bgt. The lipoxygenase, glucan exohydrolase, glucose adenylyltransferasesmall, phosphoribulokinase, and phosphoglucomutase are first reported to be involved in the interactions of wheat-Bgt at early stage. The further study of these proteins will deepen our understanding of their detailed functions and potentially develop more efficient disease control strategies.
Investigating Possible Enzymatic Degradation on Polymer Shells around Inorganic Nanoparticles
Authors: Zhu Lin , Pelaz Beatriz , Chakraborty Indranath , Parak Wolfgang J.
Published: February 2019

Inorganic iron oxide nanoparticle cores as model systems for inorganic nanoparticles were coated with shells of amphiphilic polymers, to which organic fluorophores were linked with different conjugation chemistries, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) chemistry and two types of “click chemistry”. The nanoparticle-dye conjugates were exposed to different enzymes/enzyme mixtures in order to investigate potential enzymatic degradation of the fluorophore-modified polymer shell. The release of the dyes and polymer fragments upon enzymatic digestion was quantified by using fluorescence spectroscopy. The data indicate that enzymatic cleavage of the fluorophore-modified organic surface coating around the inorganic nanoparticles in fact depends on the used conjugation chemistry, together with the types of enzymes to which the nanoparticle-dye conjugates are exposed.
Approaches towards Longevity: Reprogramming, Senolysis, and Improved Mitotic Competence as Anti-Aging Therapies
Authors: Melo Pereira Sofia , Ribeiro Rui , Logarinho Elsa
Published: February 2019

Mainstream approaches that are currently used as anti-aging therapies primarily explore the senescence and epigenetic drift aging hallmarks and they are at two ends of the spectrum. While senolytic therapies include either the selective elimination of senescent cells or the disruption of their secretome with the use of drugs or natural compounds, cellular reprogramming uses genetic manipulation to revert cells all the way back to pluripotency. Here, we describe the progress that has been made on these therapies, while highlighting the major challenges involved. Moreover, based on recent findings elucidating the impact of mitotic shutdown and aneuploidy in cellular senescence, we discuss the modulation of mitotic competence as an alternative strategy to delay the hallmarks of aging. We propose that a regulated rise in mitotic competence of cells could circumvent certain limitations that are present in the senolytic and reprogramming approaches, by acting to decelerate senescence and possibly restore the epigenetic landscape.
Start Codon Recognition in Eukaryotic and Archaeal Translation Initiation: A Common Structural Core
Authors: Schmitt Emmanuelle , Coureux Pierre-Damien , Monestier Auriane , Dubiez Etienne , Mechulam Yves
Published: February 2019

Understanding molecular mechanisms of ribosomal translation sheds light on the emergence and evolution of protein synthesis in the three domains of life. Universally, ribosomal translation is described in three steps: initiation, elongation and termination. During initiation, a macromolecular complex assembled around the small ribosomal subunit selects the start codon on the mRNA and defines the open reading frame. In this review, we focus on the comparison of start codon selection mechanisms in eukaryotes and archaea. Eukaryotic translation initiation is a very complicated process, involving many initiation factors. The most widespread mechanism for the discovery of the start codon is the scanning of the mRNA by a pre-initiation complex until the first AUG codon in a correct context is found. In archaea, long-range scanning does not occur because of the presence of Shine-Dalgarno (SD) sequences or of short 5′ untranslated regions. However, archaeal and eukaryotic translation initiations have three initiation factors in common: e/aIF1, e/aIF1A and e/aIF2 are directly involved in the selection of the start codon. Therefore, the idea that these archaeal and eukaryotic factors fulfill similar functions within a common structural ribosomal core complex has emerged. A divergence between eukaryotic and archaeal factors allowed for the adaptation to the long-range scanning process versus the SD mediated prepositioning of the ribosome.
3D-Printed Bioactive Calcium Silicate/Poly-ε-Caprolactone Bioscaffolds Modified with Biomimetic Extracellular Matrices for Bone Regeneration
Authors: Wu Yuan-Haw Andrew , Chiu Yung-Cheng , Lin Yen-Hong , Ho Chia-Che , Shie Ming-You , Chen Yi-Wen
Published: February 2019

Currently, clinically available orthopedic implants are extremely biocompatible but they lack specific biological characteristics that allow for further interaction with surrounding tissues. The extracellular matrix (ECM)-coated scaffolds have received considerable interest for bone regeneration due to their ability in upregulating regenerative cellular behaviors. This study delves into the designing and fabrication of three-dimensional (3D)-printed scaffolds that were made out of calcium silicate (CS), polycaprolactone (PCL), and decellularized ECM (dECM) from MG63 cells, generating a promising bone tissue engineering strategy that revolves around the concept of enhancing osteogenesis by creating an osteoinductive microenvironment with osteogenesis-promoting dECM. We cultured MG63 on scaffolds to obtain a dECM-coated CS/PCL scaffold and further studied the biological performance of the dECM hybrid scaffolds. The results indicated that the dECM-coated CS/PCL scaffolds exhibited excellent biocompatibility and effectively enhanced cellular adhesion, proliferation, and differentiation of human Wharton’s Jelly mesenchymal stem cells by increasing the expression of osteogenic-related genes. They also presented anti-inflammatory characteristics by showing a decrease in the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). Histological analysis of in vivo experiments presented excellent bone regenerative capabilities of the dECM-coated scaffold. Overall, our work presented a promising technique for producing bioscaffolds that can augment bone tissue regeneration in numerous aspects.
Root Proteomics Reveals the Effects of Wood Vinegar on Wheat Growth and Subsequent Tolerance to Drought Stress
Authors: Wang Yuying , Qiu Ling , Song Qilu , Wang Shuping , Wang Yajun , Ge Yihong
Published: February 2019

Wood vinegar (WV) or pyroligneous acid (PA) is a reddish-brown liquid created during the dry distillation of biomass, a process called pyrolysis. WV contains important biologically active components, which can enhance plant growth and tolerance to drought stress. However, its mechanism of action remains unknown. Our results after presoaking wheat seeds with various concentrations of WV indicate that a 1:900 WV concentration can significantly enhance growth. To investigate the response of wheat roots to drought stress, we compared quantitative proteomic profiles in the roots of wheat plants grown from seeds either presoaked (treatment) or non-presoaked (control) with WV. Our results indicated that the abscisic acid (ABA) content of wheat roots in the WV treatment was significantly increased. Reactive oxygen species (ROS) and malonaldehyde (MDA) levels roots were significantly lower than in the control treatment under drought stress, while the activity of major antioxidant enzymes was significantly increased. Two-dimensional electrophoresis (2D-PAGE) identified 138 differentially accumulated protein (DAP) spots representing 103 unique protein species responding to drought stress in wheat roots of the control and WV-treated groups. These DAPs are mostly involved in the stress response, carbohydrate metabolism, protein metabolism, and secondary metabolism. Proteome profiles showed the DAPs involved in carbohydrate metabolism, stress response, and secondary metabolism had increased accumulation in roots of the WV-treated groups. These findings suggest that the roots from wheat seeds presoaked with WV can initiate an early defense mechanism to mitigate drought stress. These results provide an explanation of how WV enhances the tolerance of wheat plants to drought stress.
Anti-Inflammatory Response and Muscarinic Cholinergic Regulation during the Laxative Effect of Asparagus cochinchinensis in Loperamide-Induced Constipation of SD Rats
Authors: Kim Ji Eun , Park Ji Won , Kang Mi Ju , Choi Hyeon Jun , Bae Su Ji , Choi You Sang , Lee Young Ju , Lee Hee Seob , Hong Jin Tae , Hwang Dae Youn
Published: February 2019

Several types of saponins and herbal plants containing saponins have been reported to have anti-inflammatory or laxative activities. To verify the therapeutic effects of saponin-enriched extracts of Asparagus cochinchinensis (SPA) on the anti-inflammatory response and on the cholinergic regulation in the gastrointestinal system, an alteration on the constipation phenotypes, on the inflammatory responses, and on the muscarinic cholinergic regulation were investigated in the transverse colons of Sprague Dawley (SD) rats with loperamide (Lop)-induced constipation after the treatment of SPA. Significant increases were observed on the total number of stools, the gastrointestinal transit, the thickness of the mucosal layer, the flat luminal surface, the number of paneth cells, and the lipid droplets in the Lop + SPA-treated group as compared to the Lop + Vehicle-treated group. SPA treatment induced the recovery of inflammatory cytokines (TNF-α, IL-1β) and IL-6), inflammatory mediators (NF-κB and iNOS), the total number of infiltered mast cells, and mucin secretion. Also, some similar improvements were observed on the levels of acetylcholine esterase (AChE) activity and on the phosphorylation of myosin light chains (MLC) as well as the expression of muscarinic acetylcholine receptors M2/M3 (mAChR M2/M3) and their mediators. The results presented herein provide the first strong evidence that SPA stimulates anti-inflammatory responses and the muscarinic cholinergic regulation when exerting its laxative effects in the chronic constipation of Lop-induced models.
β-Galactosidase from Lactobacillus helveticus DSM 20075: Biochemical Characterization and Recombinant Expression for Applications in Dairy Industry
Authors: Kittibunchakul Suwapat , Pham Mai-Lan , Tran Anh-Minh , Nguyen Thu-Ha
Published: February 2019

β-Galactosidase encoding genes lacLM from Lactobacillus helveticus DSM 20075 were cloned and successfully overexpressed in Escherichia coli and Lactobacillus plantarum using different expression systems. The highest recombinant β-galactosidase activity of ∼26 kU per L of medium was obtained when using an expression system based on the T7 RNA polymerase promoter in E. coli, which is more than 1000-fold or 28-fold higher than the production of native β-galactosidase from L. helveticus DSM 20075 when grown on glucose or lactose, respectively. The overexpression in L. plantarum using lactobacillal food-grade gene expression system resulted in ∼2.3 kU per L of medium, which is approximately 10-fold lower compared to the expression in E. coli. The recombinant β-galactosidase from L. helveticus overexpressed in E. coli was purified to apparent homogeneity and subsequently characterized. The Km and vmax values for lactose and o-nitrophenyl-β-d-galactopyranoside (oNPG) were 15.7 ± 1.3 mM, 11.1 ± 0.2 µmol D-glucose released per min per mg protein, and 1.4 ± 0.3 mM, 476 ± 66 µmol o-nitrophenol released per min per mg protein, respectively. The enzyme was inhibited by high concentrations of oNPG with Ki,s = 3.6 ± 0.8 mM. The optimum pH for hydrolysis of both substrates, lactose and oNPG, is pH 6.5 and optimum temperatures for these reactions are 60 and 55 °C, respectively. The formation of galacto-oligosaccharides (GOS) in discontinuous mode using both crude recombinant enzyme from L. plantarum and purified recombinant enzyme from E. coli revealed high transgalactosylation activity of β-galactosidases from L. helveticus; hence, this enzyme is an interesting candidate for applications in lactose conversion and GOS formation processes.
Decoding the Mechanism of Action of Rapid-Acting Antidepressant Treatment Strategies: Does Gender Matter?
Authors: Herzog David P. , Wegener Gregers , Lieb Klaus , Müller Marianne B. , Treccani Giulia
Published: February 2019

Gender differences play a pivotal role in the pathophysiology and treatment of major depressive disorder. This is strongly supported by a mean 2:1 female-male ratio of depression consistently observed throughout studies in developed nations. Considering the urgent need to tailor individualized treatment strategies to fight depression more efficiently, a more precise understanding of gender-specific aspects in the pathophysiology and treatment of depressive disorders is fundamental. However, current treatment guidelines almost entirely neglect gender as a potentially relevant factor. Similarly, the vast majority of animal experiments analysing antidepressant treatment in rodent models exclusively uses male animals and does not consider gender-specific effects. Based on the growing interest in innovative and rapid-acting treatment approaches in depression, such as the administration of ketamine, its metabolites or electroconvulsive therapy, this review article summarizes the evidence supporting the importance of gender in modulating response to rapid acting antidepressant treatment. We provide an overview on the current state of knowledge and propose a framework for rodent experiments to ultimately decode gender-dependent differences in molecular and behavioural mechanisms involved in shaping treatment response.
Analysis of Extracellular Vesicles in Gastric Juice from Gastric Cancer Patients
Authors: Kagota Shuji , Taniguchi Kohei , Lee Sang-Woong , Ito Yuko , Kuranaga Yuki , Hashiguchi Yasuyuki , Inomata Yosuke , Imai Yoshiro , Tanaka Ryo , Tashiro Keitaro , Kawai Masaru , Akao Yukihiro , Uchiyama Kazuhisa
Published: February 2019

Extracellular vesicles (EVs) are secretory membrane vesicles containing lipids, proteins, and nucleic acids; they function in intercellular transport by delivering their components to recipient cells. EVs are observed in various body fluids, i.e., blood, saliva, urine, amniotic fluid, and ascites. EVs secreted from cancer cells play important roles in the formation of their environment, including fibrosis, angiogenesis, evasion of immune surveillance, and even metastasis. However, EVs in gastric juice (GJ-EVs) have been largely unexplored. In this study, we sought to clarify the existence of GJ-EVs derived from gastric cancer patients. GJ-EVs were isolated by the ultracentrifuge method combined with our own preprocessing from gastric cancer (GC) patients. We verified GJ-EVs by morphological experiments, i.e., nanoparticle tracking system analysis and electron microscopy. In addition, protein and microRNA markers of EVs were examined by Western blotting analysis, Bioanalyzer, or quantitative reverse transcription polymerase chain reaction. GJ-EVs were found to promote the proliferation of normal fibroblast cells. Our findings suggest that isolates from the GJ of GC patients contain EVs and imply that GJ-EVs partially affect their microenvironments and that analysis using GJ-EVs from GC patients will help to clarify the pathophysiology of GC.
Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures
Authors: Nordén Rickard , Nilsson Jonas , Samuelsson Ebba , Risinger Christian , Sihlbom Carina , Blixt Ola , Larson Göran , Olofsson Sigvard , Bergström Tomas
Published: February 2019

A recombinant subunit vaccine (Shingrix®) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The subunit vaccine elicits stronger virus-specific CD4+ T cell response as well as antibody B cell response to gE, compared to the currently used live attenuated vaccine (Zostavax®). This situation is at variance with the current notion since a live vaccine, causing an active virus infection, should be far more efficient than a subunit vaccine based on only one single viral glycoprotein. We previously found gE to be heavily glycosylated, not least by numerous clustered O-linked glycans, when it was produced in human fibroblasts. However, in contrast to Zostavax®, which is produced in fibroblasts, the recombinant gE of Shingrix® is expressed in Chinese hamster ovary (CHO) cells. Hence, the glycan occupancy and glycan structures of gE may differ considerably between the two vaccine types. Here, we aimed at (i) defining the glycan structures and positions of recombinant gE and (ii) identifying possible features of the recombinant gE O-glycosylation pattern contributing to the vaccine efficacy of Shingrix®. Firstly, recombinant gE produced in CHO cells (“Shingrix situation”) is more scarcely decorated by O-linked glycans than gE from human fibroblasts (“Zostavax situation”), with respect to glycan site occupancy. Secondly, screening of immunodominant B cell epitopes of gE, using a synthetic peptide library against serum samples from VZV-seropositive individuals, revealed that the O-linked glycan signature promoted binding of IgG antibodies via a decreased number of interfering O-linked glycans, but also via specific O-linked glycans enhancing antibody binding. These findings may, in part, explain the higher protective efficacy of Shingrix®, and can also be of relevance for development of subunit vaccines to other enveloped viruses.
The Combined Use of Phenothiazines and Statins Strongly Affects Doxorubicin-Resistance, Apoptosis, and Cox-2 Activity in Colon Cancer Cells
Authors: Środa-Pomianek Kamila , Michalak Krystyna , Palko-Łabuz Anna , Uryga Anna , Świątek Piotr , Majkowski Michał , Wesołowska Olga
Published: February 2019

Since none of the multidrug resistance (MDR) modulators tested so far found their way into clinic, a novel approach to overcome the MDR of cancer cells has been proposed. The combined use of two MDR modulators of dissimilar mechanisms of action was suggested to benefit from the synergy between them. The effect of three phenothiazine derivatives that were used as single agents and in combination with simvastatin on cell growth, apoptosis induction, activity, and expression of cyclooxygenase-2 (COX-2) in doxorubicin-resistant colon cancer cells (LoVo/Dx) was investigated. Treatment of LoVo/Dx cells by phenothiazine derivatives combined with simvastatin resulted in an increase of doxorubicin cytotoxicity and its intracellular accumulation as compared to the treatment with phenothiazine derivatives that were used as single agents. Similarly, LoVo/Dx cells treated with two-component mixture of modulators showed the reduced expression of ABCB1 (P-glycoprotein) transporter and COX-2 enzyme, both on mRNA and protein level. Reduced expression of anti-apoptotic Bcl-2 protein and increased expression of pro-apoptotic Bax were also detected. Additionally, COX-2 activity was diminished, and caspase-3 activity was increased to a higher extent by phenothiazine derivative:simvastatin mixtures than by phenothiazine derivatives themselves. Therefore, the introduction of simvastatin strengthened the anti-MDR, anti-inflammatory, and pro-apoptotic properties of phenothiazines in LoVo/Dx cells.
Realizing the Clinical Potential of Immunogenic Cell Death in Cancer Chemotherapy and Radiotherapy
Authors: Rapoport Bernardo L. , Anderson Ronald
Published: February 2019

Immunogenic cell death (ICD), which is triggered by exposure of tumor cells to a limited range of anticancer drugs, radiotherapy, and photodynamic therapy, represents a recent innovation in the revitalized and burgeoning field of oncoimmunnotherapy. ICD results in the cellular redistribution and extracellular release of damage-associated molecular patterns (DAMPs), which have the potential to activate and restore tumor-targeted immune responses. Although a convincing body of evidence exists with respect to the antitumor efficacy of ICD in various experimental systems, especially murine models of experimental anticancer immunotherapy, evidence for the existence of ICD in the clinical setting is less compelling. Following overviews of hallmark developments, which have sparked the revival of interest in the field of oncoimmunotherapy, types of tumor cell death and the various DAMPs most prominently involved in the activation of antitumor immune responses, the remainder of this review is focused on strategies which may potentiate ICD in the clinical setting. These include identification of tumor- and host-related factors predictive of the efficacy of ICD, the clinical utility of combinatorial immunotherapeutic strategies, novel small molecule inducers of ICD, novel and repurposed small molecule immunostimulants, as well as the critical requirement for validated biomarkers in predicting the efficacy of ICD.
Evaluation of Mechanical and Interfacial Properties of Bio-Composites Based on Poly(Lactic Acid) with Natural Cellulose Fibers
Authors: Aliotta Laura , Gigante Vito , Coltelli Maria Beatrice , Cinelli Patrizia , Lazzeri Andrea
Published: February 2019

The circular economy policy and the interest for sustainable material are inducing a constant expansion of the bio-composites market. The opportunity of using natural fibers in bio-based and biodegradable polymeric matrices, derived from industrial and/or agricultural waste, represents a stimulating challenge in the replacement of traditional composites based on fossil sources. The coupling of bioplastics with natural fibers in order to lower costs and promote degradability is one of the primary objectives of research, above all in the packaging and agricultural sectors where large amounts of non-recyclable plastics are generated, inducing a serious problem for plastic disposal and potential accumulation in the environment. Among biopolymers, poly(lactic acid) (PLA) is one of the most used compostable, bio-based polymeric matrices, since it exhibits process ability and mechanical properties compatible with a wide range of applications. In this study, two types of cellulosic fibers were processed with PLA in order to obtain bio-composites with different percentages of microfibers (5%, 10%, 20%). The mechanical properties were evaluated (tensile and impact test), and analytical models were applied in order to estimate the adhesion between matrix and fibers and to predict the material’s stiffness. Understanding these properties is of particular importance in order to be able to tune and project the final characteristics of bio-composites.
Role of Endoplasmic Reticulum Stress in the Anticancer Activity of Natural Compounds
Authors: Limonta Patrizia , Moretti Roberta M. , Marzagalli Monica , Fontana Fabrizio , Raimondi Michela , Montagnani Marelli Marina
Published: February 2019

Cancer represents a serious global health problem, and its incidence and mortality are rapidly growing worldwide. One of the main causes of the failure of an anticancer treatment is the development of drug resistance by cancer cells. Therefore, it is necessary to develop new drugs characterized by better pharmacological and toxicological profiles. Natural compounds can represent an optimal collection of bioactive molecules. Many natural compounds have been proven to possess anticancer effects in different types of tumors, but often the molecular mechanisms associated with their cytotoxicity are not completely understood. The endoplasmic reticulum (ER) is an organelle involved in multiple cellular processes. Alteration of ER homeostasis and its appropriate functioning originates a cascade of signaling events known as ER stress response or unfolded protein response (UPR). The UPR pathways involve three different sensors (protein kinase RNA(PKR)-like ER kinase (PERK), inositol requiring enzyme1α (IRE1) and activating transcription factor 6 (ATF6)) residing on the ER membranes. Although the main purpose of UPR is to restore this organelle’s homeostasis, a persistent UPR can trigger cell death pathways such as apoptosis. There is a growing body of evidence showing that ER stress may play a role in the cytotoxicity of many natural compounds. In this review we present an overview of different plant-derived natural compounds, such as curcumin, resveratrol, green tea polyphenols, tocotrienols, and garcinia derivates, that exert their anticancer activity via ER stress modulation in different human cancers.
Transcriptional Dynamics of Grain Development in Barley (Hordeum vulgare L.)
Authors: Bian Jianxin , Deng Pingchuan , Zhan Haoshuang , Wu Xiaotong , Nishantha Mutthanthirige D. L. C. , Yan Zhaogui , Du Xianghong , Nie Xiaojun , Song Weining
Published: February 2019

Grain development, as a vital process in the crop’s life cycle, is crucial for determining crop quality and yield. However, the molecular basis and regulatory network of barley grain development is not well understood at present. Here, we investigated the transcriptional dynamics of barley grain development through RNA sequencing at four developmental phases, including early prestorage phase (3 days post anthesis (DPA)), late prestorage or transition phase (8 DPA), early storage phase (13 DPA), and levels off stages (18 DPA). Transcriptome profiling found that pronounced shifts occurred in the abundance of transcripts involved in both primary and secondary metabolism during grain development. The transcripts’ activity was decreased during maturation while the largest divergence was observed between the transitions from prestorage phase to storage phase, which coincided with the physiological changes. Furthermore, the transcription factors, hormone signal transduction-related as well as sugar-metabolism-related genes, were found to play a crucial role in barley grain development. Finally, 4771 RNA editing events were identified in these four development stages, and most of the RNA editing genes were preferentially expressed at the prestore stage rather than in the store stage, which was significantly enriched in “essential” genes and plant hormone signal transduction pathway. These results suggested that RNA editing might act as a ‘regulator’ to control grain development. This study systematically dissected the gene expression atlas of barley grain development through transcriptome analysis, which not only provided the potential targets for further functional studies, but also provided insights into the dynamics of gene regulation underlying grain development in barley and beyond.
Taste Receptors: New Players in Sperm Biology
Authors: Luddi Alice , Governini Laura , Wilmskötter Dorke , Gudermann Thomas , Boekhoff Ingrid , Piomboni Paola
Published: February 2019

Taste receptors were first described as sensory receptors located on the tongue, where they are expressed in small clusters of specialized epithelial cells. However, more studies were published in recent years pointing to an expression of these proteins not only in the oral cavity but throughout the body and thus to a physiological role beyond the tongue. The recent observation that taste receptors and components of the coupled taste transduction cascade are also expressed during the different phases of spermatogenesis as well as in mature spermatozoa from mouse to humans and the overlap between the ligand spectrum of taste receptors with compounds in the male and female reproductive organs makes it reasonable to assume that sperm “taste” these different cues in their natural microenvironments. This assumption is assisted by the recent observations of a reproductive phenotype of different mouse lines carrying a targeted deletion of a taste receptor gene as well as the finding of a significant correlation between human male infertility and some polymorphisms in taste receptors genes. In this review, we depict recent findings on the role of taste receptors in male fertility, especially focusing on their possible involvement in mechanisms underlying spermatogenesis and post testicular sperm maturation. We also highlight the impact of genetic deletions of taste receptors, as well as their polymorphisms on male reproduction.
Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-Onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer
Authors: Álvaro Edurne , Cano Juana M. , García Juan L. , Brandáriz Lorena , Olmedillas-López Susana , Arriba María , Rueda Daniel , Rodríguez Yolanda , Cañete Ángel , Arribas Julia , Inglada-Pérez Lucía , Pérez Jessica , Gómez Carlos , García-Arranz Mariano , García-Olmo Damián , Goel Ajay , Urioste Miguel , González-Sarmiento Rogelio , Perea José
Published: February 2019

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification.
A Modified Robust FCM Model with Spatial Constraints for Brain MR Image Segmentation
Authors: Song Jianhua , Zhang Zhe
Published: February 2019

In brain magnetic resonance (MR) images, image quality is often degraded due to the influence of noise and outliers, which brings some difficulties for doctors to segment and extract brain tissue accurately. In this paper, a modified robust fuzzy c-means (MRFCM) algorithm for brain MR image segmentation is proposed. According to the gray level information of the pixels in the local neighborhood, the deviation values of each adjacent pixel are calculated in kernel space based on their median value, and the normalized adaptive weighted measure of each pixel is obtained. Both impulse noise and Gaussian noise in the image can be effectively suppressed, and the detail and edge information of the brain MR image can be better preserved. At the same time, the gray histogram is used to replace single pixel during the clustering process. The results of segmentation of MRFCM are compared with the state-of-the-art algorithms based on fuzzy clustering, and the proposed algorithm has the stronger anti-noise property, better robustness to various noises and higher segmentation accuracy.
Molecular Thermodynamics Using Nuclear Magnetic Resonance (NMR) Spectroscopy
Authors: Krishnan Viswanathan V.
Published: February 2019

Nuclear magnetic resonance (NMR) spectroscopy is perhaps the most widely used technology from the undergraduate teaching labs in organic chemistry to advanced research for the determination of three-dimensional structure as well as dynamics of biomolecular systems... The NMR spectrum of a molecule under a given experimental condition is unique, providing both quantitative and structural information. In particular, the quantitative nature of NMR spectroscopy offers the ability to follow a reaction pathway of the given molecule in a dynamic process under well-defined experimental conditions. To highlight the use of NMR when determining the molecular thermodynamic parameters, a review of three distinct applications developed from our laboratory is presented. These applications include the thermodynamic parameters of (a) molecular oxidation from time-dependent kinetics, (b) intramolecular rotation, and (c) intermolecular exchange. An experimental overview and the method of data analysis are provided so that these applications can be adopted in a range of molecular systems.
Central Nervous System Effects of Oral Propranolol for Infantile Hemangioma: A Systematic Review and Meta-Analysis
Authors: Thai Thuy , Wang Ching-Yu , Chang Ching-Yuan , Brown Joshua D.
Published: February 2019

Concerns about the effects of propranolol on the central nervous system (CNS) in the infantile hemangioma (IH) population have been raised. We conducted a meta-analysis of the CNS and sleep-related effects of oral propranolol in IH patients. PubMed, Embase, Cochrance, Web of Science, and Clinicaltrials.gov were searched for relevant studies. We included clinical trials that compared oral propranolol with other treatments among IH patients under 6 years old and monitored and reported any adverse events. Study characteristics, types and number of adverse events were abstracted. Cochrane Collaboration Risk of Bias Tool was used to assess risk of bias. Our main outcomes were CNS and sleep-related effects. Random-effects models were used to estimate the pooled risk ratio. We did not observe statistically significant associations between oral propranolol and CNS or sleep-related effects. Oral propranolol appeared to have a safer profile of CNS effects than corticosteroids (RR = 0.27, 95% CI 0.02–3.00), but had an increased risk versus non-corticosteroids (for CNS effect, RR = 1.40, 95% CI 0.86–2.27; for sleep-related effects, RR = 1.63, 95% CI 0.88–3.03). Despite no statistically significant associations, there were suggestive findings of increased CNS effects and sleep-related risk of propranolol versus non-corticosteroids. In practice, CNS and sleep-related events should be monitored more closely among IH patients treated with oral propranolol.
Evaluation of Material Appearance Under Different Spotlight Distributions Compared to Natural Illumination
Authors: Yamazoe Takashi , Funaki Tomohiro , Kiyasu Yuki , Mizokami Yoko
Published: February 2019

Solid-state lamps including Organic Light Emitting Diode (OLED) lighting could facilitate a wide variety of lighting conditions by controlling the spectral power distribution and the spatial distribution of the light source. The appearance of the surface of an object is significantly influenced by the lighting conditions and the constituent materials of the objects. Therefore, appearance of objects may appear to be different from expectation. Lighting condition leads to important part of accurate material recognition. We investigate whether it is possible to determine the lighting condition that results in the intended material appearance by the evaluation of this parameter under different lighting distributions compared to natural illumination. The viewing conditions of three spotlight sizes and three illuminance levels were investigated. The participants selected the viewing condition for which the appearance of fruits and vegetable food samples was the closest to the impressions learned from observing and freely holding these objects under natural reference illumination. Participants also evaluated their impressions of stimuli in each viewing condition by responding to twelve questions. The results show that the wide spotlight size condition with higher diffuseness of the illumination was selected more frequently than the narrow spotlight conditions. This suggests that the diffuseness of illumination influences the appearance of the object’s material. The results of seven-point scales suggest that their impression of stimuli was influenced by the surface properties of the objects as well as the lighting distributions. It was suggested that it is possible to set an appropriate lighting condition to facilitate material appearance similar to the expected appearance under natural illumination.
Linking Cellular Morphogenesis with Antifungal Treatment and Susceptibility in Candida Pathogens
Authors: Sharma Jehoshua , Rosiana Sierra , Razzaq Iqra , Shapiro Rebecca S.
Published: February 2019

Fungal infections are a growing public health concern, and an increasingly important cause of human mortality, with Candida species being amongst the most frequently encountered of these opportunistic fungal pathogens. Several Candida species are polymorphic, and able to transition between distinct morphological states, including yeast, hyphal, and pseudohyphal forms. While not all Candida pathogens are polymorphic, the ability to undergo morphogenesis is linked with the virulence of many of these pathogens. There are also many connections between Candida morphogenesis and antifungal drug treatment and susceptibility. Here, we review how Candida morphogenesis—a key virulence trait—is linked with antifungal drugs and antifungal drug resistance. We highlight how antifungal therapeutics are able to modulate morphogenesis in both sensitive and drug-resistant Candida strains, the shared signaling pathways that mediate both morphogenesis and the cellular response to antifungal drugs and drug resistance, and the connection between Candida morphology, drug resistance, and biofilm growth. We further review the development of anti-virulence drugs, and targeting Candida morphogenesis as a novel therapeutic strategy to target fungal pathogens. Together, this review highlights important connections between fungal morphogenesis, virulence, and susceptibility to antifungals.
Chronic Pulmonary Aspergillosis in Patients with Underlying Respiratory Disorders in Cuba—A Pilot Study
Authors: Beltrán Rodríguez Nathalie , San Juan-Galán Javier Luis , Fernández Andreu Carlos Manuel , María Yera Dulce , Barrios Pita Miriam , Perurena Lancha Mayda Rosa , Velar Martínez Rosario Esperanza , Illnait Zaragozí María Teresa , Martínez Machín Gerardo Félix
Published: February 2019

Chronic pulmonary aspergillosis (CPA) is a fungal infection with high mortality and morbidity rates. This disease is caused by several Aspergillus species and affects patients with an underlying respiratory condition. This pilot study aims to recognize CPA among patients with different respiratory diseases. Twenty-one out of 47 patients were classified as CPA based on the examination of clinical signs and symptoms, radiological findings, mycological culture of respiratory samples and analysis of Aspergillus IgG antibodies. There was a close association between high levels of Aspergillus IgG antibodies and the presence of cavities. Although Aspergillus flavus was the predominant species among clinical isolates, the number of isolates was small to reach conclusions on the prevalence of this species as main cause of CPA in Cuba. From the eleven evaluable patients for the treatment with itraconazole (Lozartil®), nine improved their health status while two did not show any recovery. This drug is included in the therapy schemes for aspergillosis in Cuba.
Experimental Investigations on the Properties of Epoxy-Resin-Bonded Cement Concrete Containing Sea Sand for Use in Unreinforced Concrete Applications
Authors: Natarajan Sakthieswaran , Neelakanda Pillai Nagendran , Murugan Sophia
Published: February 2019

This paper deals with the experimental studies conducted on the effects of using sea sand on the properties of polymer concrete modified using epoxy resin. The physical properties including workability, mechanical properties, and durability properties were evaluated as a function of sea-sand substitution. The results obtained behave as strong evidence for the feasibility of using sea sand as fine aggregate to solve the problem associated with the exhaustion of natural aggregates when used in combination with epoxy polymer. A clear understanding of the behavior of polymer concrete with sea sand as aggregate was obtained through some preliminary investigations. The test results showed a significant improvement in the compressive and flexural strength due to the sea-sand substitution in polymer concrete. Resistance to the water intrusion was also improved for the concrete mixes due to the inclusion of epoxy resin. The quality and the integrity of the concrete were also improved, as evident from the SEM analysis and infrared (IR) spectroscopy, and the results function as solid basis for the use of sea-sand polymer-modified concrete for practical applications. Results also show that 15% replacement of fine aggregate by sea sand in air-cured polymer concrete exhibited enhanced strength and durability properties; thus, the produced concrete can be an effective material for unreinforced concrete applications.
Creep, Hardness, and Elastic Modulus of Lingual Fixed Retainer Adhesives
Authors: Hassan Manar N. , Zinelis Spiros , Hersberger-Zurfluh Monika , Eliades Theodore
Published: February 2019

The aims of this study were twofold: a) to characterize a wide array of time-independent and -dependent properties and b) to find possible correlations among the properties tested. Seven commercially available orthodontic adhesives were included in this study and ten cylindrical specimens were prepared from each material. Five specimens from each material were used for the characterization of Martens Hardness (HM), indentation modulus (EIT), and elastic index (ηIT), and the remaining five for the determination of indentation creep (CIT). Al the aforementioned properties were identified by employing an Instrumented Indentations Testing (IIT) device with a Vickers indenter. The results of HM, EIT, ηIT, and CIT were statistically analyzed by one way ANOVA and Tukey post hoc test, while the possible correlations among the aforementioned properties were determined by Spearman correlation test. Statistical significant differences were identified for all properties among the materials tested. Spearman correlation reveals that HM has a positive correlation with EIT. Both properties demonstrated a negative correlation with ηIT and CIT, while no correlation was identified between ηIT and CIT. Significant differences in the mechanical properties tested may also imply differences in their clinical behavior and efficacy.
Method for Resistivity Measurement of Grainy Carbon and Graphite Materials
Authors: Janerka Krzysztof , Jezierski Jan , Stawarz Marcin , Szajnar Jan
Published: February 2019

The article presents the issue of electrical resistivity measurement of carbon materials. The device that was developed by the authors is described and is the subject of a Polish patent. The innovative approach of the setup is based on the possibility of measuring the resistivity of grainy (powdered, dusty) materials without having to conduct their preliminary pressing. The material that is to be analyzed is placed inside the chamber made of electrically non-conducting material. The sample is then compacted with pneumatically driven pistons and the compaction force can be controlled by the air pressure. The device as proposed by the authors works at a pressure of 900 kPa, which is equal to the compaction force of 1.2 kN. Resistivity is calculated on the basis of the voltage drop recorded on the sample length. The research covers the analysis of the influence of carbon material grade and compaction force on the resistivity value. It was stated that the resistivity of the graphite materials that were analyzed here changed within the range of 43–172 µm: petroleum coke—360–780 µm; the anthracite—1900–3900 µm. The experimental method presented here can be used whenever carbon materials are present in the form of grains.