bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary cholesterol and apolipoprotein A-I are trafficked in endosomes and lysosomes in the live zebrafish intestine
Authors: Otis Jessica P. , Shen Meng-Chieh , Caldwell Blake A. , Reyes Gaido Oscar E. , Farber Steven A.
Published: January 2019

Difficulty in imaging the vertebrate intestine in vivo has hindered our ability to model nutrient and protein trafficking from both the lumenal and basolateral aspects of enterocytes. Our goal was to use live confocal imaging to increase understanding of intestinal trafficking of dietary cholesterol and apolipoprotein A-I (APOA-I), the main structural component of high-density lipoproteins. We developed a novel assay to visualize live dietary cholesterol trafficking in the zebrafish intestine by feeding TopFluor-cholesterol (TF-cholesterol), a fluorescent cholesterol analog, in a lipid-rich, chicken egg yolk feed. Quantitative microscopy of transgenic zebrafish expressing fluorescently tagged protein markers of early, recycling, and late endosomes/lysosomes provided the first evidence, to our knowledge, of cholesterol transport in the intestinal endosomal-lysosomal trafficking system. To study APOA-I dynamics, transgenic zebrafish expressing an APOA-I fluorescent fusion protein (APOA-I-mCherry) from tissue-specific promoters were created. These zebrafish demonstrated that APOA-I-mCherry derived from the intestine accumulated in the liver and vice versa. Additionally, intracellular APOA-I-mCherry localized to endosomes and lysosomes in the intestine and liver. Moreover, live imaging demonstrated that APOA-I-mCherry colocalized with dietary TF-cholesterol in enterocytes, and this colocalization increased with feeding time. This study provides a new set of tools for the study of cellular lipid biology and elucidates a key role for endosomal-lysosomal trafficking of intestinal cholesterol and APOA-I.

NEW & NOTEWORTHY A fluorescent cholesterol analog was fed to live, translucent larval zebrafish to visualize intracellular cholesterol and apolipoprotein A-I (APOA-I) trafficking. With this model intestinal endosomal-lysosomal cholesterol trafficking was observed for the first time. A new APOA-I fusion protein (APOA-I-mCherry) expressed from tissue-specific promoters was secreted into the circulation and revealed that liver-derived APOA-I-mCherry accumulates in the intestine and vice versa. Intestinal, intracellular APOA-I-mCherry was observed in endosomes and lysosomes and colocalized with dietary cholesterol.
Lethal avian influenza A (H5N1) virus replicates in pontomedullary chemosensitive neurons and depresses hypercapnic ventilatory response in mice
Authors: Zhuang Jianguo , Zang Na , Ye Chunyan , Xu Fadi
Published: January 2019

The highly pathogenic H5N1 (HK483) viral infection causes a depressed hypercapnic ventilatory response (dHCVR, 20%↓) at 2 days postinfection (dpi) and death at 7 dpi in mice, but the relevant mechanisms are not fully understood. Glomus cells in the carotid body and catecholaminergic neurons in locus coeruleus (LC), neurokinin 1 receptor (NK1R)-expressing neurons in the retrotrapezoid nucleus (RTN), and serotonergic neurons in the raphe are chemosensitive and responsible for HCVR. We asked whether the dHCVR became worse over the infection period with viral replication in these cells/neurons. Mice intranasally inoculated with saline or the HK483 virus were exposed to hypercapnia for 5 min at 0, 2, 4, or 6 dpi, followed by immunohistochemistry to determine the expression of nucleoprotein of H5N1 influenza A (NP) alone and coupled with 1) tyrosine hydroxylase (TH) in the carotid body and LC, 2) NK1R in the RTN, and 3) tryptophan hydroxylase (TPH) in the raphe. HK483 viral infection blunted HCVR by ∼20, 50, and 65% at 2, 4, and 6 dpi. The NP was observed in the pontomedullary respiratory-related nuclei (but not in the carotid body) at 4 and 6 dpi, especially in 20% of RTN NK1R, 35% of LC TH, and ∼10% raphe TPH neurons. The infection significantly reduced the local NK1R or TPH immunoreactivity and population of neurons expressing NK1R or TPH. We conclude that the HK483 virus infects the pontomedullary respiratory nuclei, particularly chemosensitive neurons in the RTN, LC, and raphe, contributing to the severe depression of HCVR and respiratory failure at 6 dpi.
Small airway hyperresponsiveness in COPD: relationship between structure and function in lung slices
Authors: Maarsingh Harm , Bidan Cécile M. , Brook Bindi S. , Zuidhof Annet B. , Elzinga Carolina R.S. , Smit Marieke , Oldenburger Anouk , Gosens Reinoud , Timens Wim , Meurs Herman
Published: January 2019

The direct relationship between pulmonary structural changes and airway hyperresponsiveness (AHR) in chronic obstructive pulmonary disease (COPD) is unclear. We investigated AHR in relation to airway and parenchymal structural changes in a guinea pig model of COPD and in COPD patients. Precision-cut lung slices (PCLS) were prepared from guinea pigs challenged with lipopolysaccharide or saline two times weekly for 12 wk. Peripheral PCLS were obtained from patients with mild to moderate COPD and non-COPD controls. AHR to methacholine was measured in large and small airways using video-assisted microscopy. Airway smooth muscle mass and alveolar airspace size were determined in the same slices. A mathematical model was used to identify potential changes in biomechanical properties underlying AHR. In guinea pigs, lipopolysaccharide increased the sensitivity of large (>150 μm) airways toward methacholine by 4.4-fold and the maximal constriction of small airways (<150 μm) by 1.5-fold. Similarly increased small airway responsiveness was found in COPD patients. In both lipopolysaccharide-challenged guinea pigs and patients, airway smooth muscle mass was unaltered, whereas increased alveolar airspace correlated with small airway hyperresponsiveness in guinea pigs. Fitting the parameters of the model indicated that COPD weakens matrix mechanical properties and enhances stiffness differences between the airway and the parenchyma, in both species. In conclusion, this study demonstrates small airway hyperresponsiveness in PCLS from COPD patients. These changes may be related to reduced parenchymal retraction forces and biomechanical changes in the airway wall. PCLS from lipopolysaccharide-exposed guinea pigs may be useful to study mechanisms of small airway hyperresponsiveness in COPD.
Tumor-suppressive effects of microRNA-181d-5p on non-small-cell lung cancer through the CDKN3-mediated Akt signaling pathway in vivo and in vitro
Authors: Gao Li-Ming , Zheng Yue , Wang Ping , Zheng Lei , Zhang Wen-Li , Di Ya , Chen Lan-Lan , Yin Xiao-Bo , Tian Qi , Shi Shan-Shan , Xu Shu-Feng
Published: January 2019

The involvement of several microRNAs (miRs) in the initiation and development of tumors through the suppression of the target gene expression has been highlighted. The aberrant expression of miR-181d-5p and cyclin-dependent kinase inhibitor 3 (CDKN3) in non-small-cell lung cancer (NSCLC) was then screened by microarray analysis. In the present study, we performed a series of in vivo and in vitro experiments for the purpose of investigating their roles in NSCLC and the underlying mechanism. There was a high expression of CDKN3, whereas miR-181d-5p was downregulated in NSCLC. Quantitative RT-PCR, Western blot analysis, and dual-luciferase reporter gene assay further identified that CDKN3 could be negatively regulated by miR-181d-5p. Moreover, the upregulation of miR-181d-5p or silencing of CDKN3 could inactivate the Akt signaling pathway. A549 with the lowest miR-181d-5p and H1975 with the highest CDKN3 among the five NSCLC cell lines (H1299, A549, H1975, NCI-H157, and GLC-82) were adopted for in vitro experiments, in which expression of miR-181d-5p and CDKN3 was altered by transfection of miR-181d-5p mimic/inhibitor or siRNA-targeting CDKN3. Afterwards, cell proliferation, apoptosis, invasion, migration, and angiogenesis, as well as epithelial-mesenchymal transition (EMT), were evaluated, and tumorigenicity was assessed. In addition, an elevation in miR-181d-5p or depletion in CDKN3 led to significant reductions in proliferation, invasion, migration, angiogenesis, EMT, and tumorigenicity of NSCLC cells, coupling with increased cell apoptosis. In conclusion, this study highlights the tumor-suppressive effects of miR-181d-5p on NSCLC via Akt signaling pathway inactivation by suppressing CDKN3, thus providing a promising therapeutic strategy for the treatment of NSCLC.
Subcutaneous administration of neutralizing antibodies to endothelial monocyte-activating protein II attenuates cigarette smoke-induced lung injury in mice
Authors: Koike Kengo , Beatman Erica L. , Schweitzer Kelly S. , Justice Matthew J. , Mikosz Andrew M. , Ni Kevin , Clauss Matthias A. , Petrache Irina
Published: January 2019

Proapoptotic and monocyte chemotactic endothelial monocyte-activating protein 2 (EMAPII) is released extracellularly during cigarette smoke (CS) exposure. We have previously demonstrated that, when administered intratracheally during chronic CS exposures, neutralizing rat antibodies to EMAPII inhibited endothelial cell apoptosis and lung inflammation and reduced airspace enlargement in mice (DBA/2J strain). Here we report further preclinical evaluation of EMAPII targeting using rat anti-EMAPII antibodies via either nebulization or subcutaneous injection. Both treatment modalities efficiently ameliorated emphysema-like disease in two different strains of CS-exposed mice, DBA/2J and C57BL/6. Of relevance for clinical applicability, this treatment showed therapeutic and even curative potential when administered either during or following CS-induced emphysema development, respectively. In addition, a fully humanized neutralizing anti-EMAPII antibody administered subcutaneously to mice during CS exposure retained anti-apoptotic and anti-inflammatory effects similar to that of the parent rat antibody. Furthermore, humanized anti-EMAPII antibody treatment attenuated CS-induced autophagy and restored mammalian target of rapamycin signaling in the lungs of mice, despite ongoing CS exposure. Together, our results demonstrate that EMAPII secretion is involved in CS-induced lung inflammation and cell injury, including apoptosis and autophagy, and that a humanized EMAPII neutralizing antibody may have therapeutic potential in emphysema.
Fractal dimension and directional analysis of elastic and collagen fiber arrangement in unsectioned arterial tissues affected by atherosclerosis and aging
Authors: Mostaço-Guidolin Leila B. , Smith Michael S. D. , Hewko Mark , Schattka Bernie , Sowa Michael G. , Major Arkady , Ko Alex C.-T.
Published: January 2019

Structural proteins like collagen and elastin are major constituents of the extracellular matrix (ECM). ECM degradation and remodeling in diseases significantly impact the microorganization of these structural proteins. Therefore, tracking the changes of collagen and elastin fiber morphological features within ECM impacted by disease progression could provide valuable insight into pathological processes such as tissue fibrosis and atherosclerosis. Benefiting from its intrinsic high-resolution imaging power and superior biochemical specificity, nonlinear optical microscopy (NLOM) is capable of providing information critical to the understanding of ECM remodeling. In this study, alterations of structural fibrillar proteins such as collagen and elastin in arteries excised from atherosclerotic rabbits were assessed by the combination of NLOM images and textural analysis methods such as fractal dimension (FD) and directional analysis (DA). FD and DA were tested for their performance in tracking the changes of extracellular elastin and fibrillar collagen remodeling resulting from atherosclerosis progression/aging. Although other methods of image analysis to study the organization of elastin and collagen structures have been reported, the simplified calculations of FD and DA presented in this work prove that they are viable strategies for extracting and analyzing fiber-related morphology from disease-impacted tissues. Furthermore, this study also demonstrates the potential utility of FD and DA in studying ECM remodeling caused by other pathological processes such as respiratory diseases, several skin conditions, or even cancer.

NEW & NOTEWORTHY Textural analyses such as fractal dimension (FD) and directional analysis (DA) are straightforward and computationally viable strategies to extract fiber-related morphological data from optical images. Therefore, objective, quantitative, and automated characterization of protein fiber morphology in extracellular matrix can be realized by using these methods in combination with digital imaging techniques such as nonlinear optical microscopy (NLOM), a highly effective visualization tool for fibrillar collagen and elastic network. Combining FD and DA with NLOM is an innovative approach to track alterations of structural fibrillar proteins. The results illustrated in this study not only prove the effectiveness of FD and DA methods in extracellular protein characterization but also demonstrate their potential value in clinical and basic biomedical research where protein microstructure characterization is critical.
Portable Multispectral System Based on Color Detector for the Analysis of Homogeneous Surfaces
Authors: Martínez-Olmos A. , Olmos P. M. , Erenas M. M. , Escobedo P.
Published: January 2019

In this work, a compact affordable and portable spectral imaging system is presented. The system is intended to be employed in general applications, such as material classification or determination of the concentration of chemical species together with colorimetric sensors. The imaging device is reduced to a small digital color detector with an active area of 3×2 mm2. This device provides a quantification of the incident emission in the form of four digital words corresponding to its averaged components blue, green, red, and near infrared. In this way, the size of the image is reduced to one pixel. The wavelength selection is carried out by means of a LED array disposed surrounding the color detector. The LEDs are selected to cover the wavelength range from 360 to 890 nm. A sequential measurement protocol is followed, and the generated data is transmitted to an external portable device via a Bluetooth link where a classification protocol is implemented in a custom-developed Android™ application. The presented system has been applied in three different scenarios involving material classification, meat freshness monitoring, and chemical analysis. The analysis of the data using principal components shows that it is possible to find a set of wavelengths where the classification of the samples is optimal.
Chemical Compositions of Metals in Bhasmas and Tibetan Zuotai Are a Major Determinant of Their Therapeutic Effects and Toxicity
Authors: Liu Jie , Zhang Feng , Ravikanth Velagapudi , Olajide Olumayokun A. , Li Cen , Wei Li-Xin
Published: January 2019

Minerals are alchemically processed as Bhasmas in Ayurvedic medicines or as Zuotai in Tibetan medicines. Ayurveda is a knowledge system of longevity and considers the mineral elixir made from “nature” capable of giving humans perpetual life. Herbo-metallic preparations have a long history in the treatment of various diseases in India, China, and around the world. Their disposition, pharmacology, efficacy, and safety require scientific evaluation. This review discusses the Bhasmas in Ayurvedic medicines and Zuotai in Tibetan medicines for their occurrence, bioaccessibility, therapeutic use, pharmacology, toxicity, and research perspectives. A literature search on Mineral, Bhasma, Ayurvedic medicine, Zuotai, Tibetan medicine, and Metals/metalloids from PubMed, Google and other sources was carried out, and the relevant papers on their traditional use, pharmacology, and toxicity were selected and analyzed. Minerals are processed to form Bhasma or Zuotai to alter their physiochemical properties distinguishing them from environmental metals. The metals found in Ayurveda are mainly from the intentional addition in the form of Bhasma or Zuotai. Bhasma and Zuotai are often used in combination with other herbals and/or animal-based products as mixtures. The advanced technologies are now utilized to characterize herbo-metallic preparations as Quality Assurance/Quality Control. The bioaccessibility, absorption, distribution, metabolism, and elimination of herbo-metallic preparations are different from environmental metals. The pharmacological basis of Bhasma in Ayurveda and Zuotai in Tibetan medicines and their interactions with drugs require scientific research. Although the toxic potentials of Bhasma and Zuotai differ from environmental metals, the metal poisoning case reports, especially lead (Pb), mercury (Hg), and arsenic (As) from inappropriate use of traditional medicines, are increasing, and pharmacovigilance is desired. In risk assessment, chemical forms of metals in Bhasma and Zuotai should be considered for their disposition, efficacy, and toxicity.
Proximity Effects on Characteristics of Flow around Three Inline Square Cylinders
Authors: Abbasi Waqas Sarwar , Islam Shams Ul , Rahman Hamid
Published: January 2019

This work presents the numerical investigations performed to study the proximity effects on fluid flow characteristics around three inline square cylinders using the lattice Boltzmann method. For this purpose the gap spacing (g) is systematically varied in the range 0.5 to 16 diameters of cylinder by keeping Reynolds number fixed at 200. Five different flow patterns are observed at different values of spacing: bluff body flow, gap trapped flow, irregular flow, alternate shedding, and modulated shedding. These patterns have a significant effect on flow induced forces and vortex shedding frequency. The spacing value g = 2 is found to be critical due to sudden changes in fluid flow characteristics. The flow parameters of first cylinder are found to be closer to single cylinder values but for middle and third cylinder the differences confirm the wake interference effect even at large values of spacing.
Phase Equilibria and Phase Diagrams for the Aqueous Ternary System Containing Sodium, Chloride, and Metaborate Ions at 288.15 and 308.15 K and 0.1 MPa
Authors: Cui Wanjing , Hou Hongfang , Hu Jiayin , Guo Yafei , Deng Tianlong
Published: January 2019

Salt-water phase diagram of the ternary system (NaCl + NaBO2 + H2O) is significant in separate boron resources from brine. Solubilities and physicochemical properties bifurcated to density and refractive index for the ternary system at 288.15 and 308.15 K and 0.1 MPa were investigated experimentally by means of isothermal dissolution. According to the experimental data, the phase diagrams for this system at two temperatures were constructed and their physicochemical properties were drawn. There both contain two invariant points, three univariant isotherm dissolution curves, and three crystallization regions corresponding to sodium metaborate tetrahydrate (NaBO2·4H2O, Smt), double salt teepleite (NaCl·NaBO2·2H2O, Te), and halite (NaCl, Ha) for (NaCl + NaBO2 + H2O). At the invariant points of this ternary system, the coexisting solid phases are both for (Smt + Te) and (Te + Ha), respectively. It was found that the double salt of teepleite was incongruent at 288.15 K and then transformed into congruent at 308.15 K. Comparing the phase diagrams at 288.15 and 308.15 K, it reveals that the area of the crystallization region of NaBO2·4H2O decreased with the increase of temperature obviously, while the area of NaCl·NaBO2·2H2O increased sharply and that of NaCl increased lightly. The refractive indices and densities of the system at two temperatures are similarly increased firstly and then decreased with the increase of NaCl concentration in the solution and attain extreme points at both invariant points. Besides, the calculated values of densities and refractive indices utilizing the empirical equations are in accordance with the experimental data at 288.15 and 308.15 K.
Multiobjective Optimal Formulations for Bus Fleet Size of Public Transit under Headway-Based Holding Control
Authors: Liang Shidong , Ma Minghui , He Shengxue
Published: January 2019

In recent years, with the development of advanced technologies for data collection, real-time bus control strategies have been implemented to improve the daily operation of transit systems, especially headway-based holding control which is a proven strategy to reduce bus bunching and improve service reliability for high-frequency bus routes, with the concept of regulating headways between successive buses. This hot topic has inspired the reconsideration of the traditional issue of fleet size optimization and the integrated bus holding control strategy. The traditional headway-based control method only focused on the regulation of bus headways, without considering the number of buses on the route. The number of buses is usually assumed as a given in advance and the task of the control method is to regulate the headways between successive buses. They did not consider the bus fleet size problem integrated with headway-based holding control method. Therefore, this work has presented a set of optimal control formulations to minimize the costs for the passengers and the bus company through calculating the optimal number of buses and the dynamic holding time, taking into account the randomness of passenger arrivals. A set of equations were formulated to obtain the operation of the buses with headway-based holding control or the schedule-based control method. The objective was to minimize the total cost for the passengers and the bus company in the system, and a Monte Carlo simulation based solution method was subsequently designed to solve the optimization model. The effects of this optimization method were tested under different operational settings. A comparison of the total costs was conducted between the headway-based holding control and the schedule-based holding control. It was found that the model was capable of reducing the costs of the bus company and passengers through utilizing headway-based bus holding control combined with optimization of the bus fleet size. The proposed optimization model could minimize the number of buses on the route for a guaranteed service level, alleviating the problem of redundant bus fleet sizes caused by bus bunching in the traditional schedule-based control method.
Bandage Contact Lens Application Reduces Fibrotic Wound Healing of Flap Margins after FS-LASIK: A Prospective Randomized Clinical Trial
Authors: Zhao Li-Quan , Li Liang-Mao , Liu Jun , Li Peng
Published: January 2019

Purpose. To assess the efficacy of applying bandage contact lens (BCL) in reducing the fibrotic healing response of flap margins following femtosecond laser in situ keratomileusis (FS-LASIK).Methods. In this prospective, randomized, interventional, observer-masked trial, 41 patients (82 eyes) with myopia and/or myopic astigmatism were scheduled to undergo FS-LASIK. After surgery, patients were fitted with a BCL in one eye (BCL eyes,n=41) but not in the contralateral eye (control eyes,n=41), following randomized allocation of the BCL to the left or right eye of each patient. The BCL was left in place overnight and removed the following morning. All eyes subsequently received standardized postoperative treatments. Patients were followed up for 6 months. We evaluated patients’ self-reported postoperative symptom scores for pain, photophobia, tearing, and foreign-body sensation. At 6 months after surgery, we examined the corneal flap margin and adjacent regions, and photographed them using slit-lamp biomicroscopy, to subjectively evaluate the wound healing response.Results. Postoperative pain and photophobia were milder in the BCL group than in the control group (P=0.041andP=0.003, respectively), but patients felt more foreign-body sensation in the eye with a BCL than in the control eye (P=0.001). There was no significant difference in tearing score between BCL eyes and control eyes (P=0.118). Regarding the fibrotic healing response of the flap margin, control eyes showed a wide, bright peripheral circumferential band with a spiculated edge and high reflectivity; conversely, BCL eyes showed a markedly narrower and smoother peripheral circumferential band, with a less spiculated edge and lower reflectivity (P<0.001).Conclusion. Patients felt less discomfort in eyes treated with a BCL after FS-LASIK than in control eyes. BCL-treated eyes also had a less intense wound healing response at the flap margins than control eyes in some of patients. BCLs may merit consideration as a treatment option after FS-LASIK for special patients. This trial is registered withChiCTR1800016579.
What Is the Biological Function of Uric Acid? An Antioxidant for Neural Protection or a Biomarker for Cell Death
Authors: Liu Dequan , Yun Yu , Yang Dechun , Hu Xinyu , Dong Xianxiang , Zhang Nan , Zhang Lumei , Yin Hua , Duan Weigang
Published: January 2019

The main aim of the present study was to investigate the biological function of uric acid. The level of uric acid in different organs in normal male rats was determined with uric acid assay kits, and the expression level of genes in the organs was determined by RNA quantitative sequencing. The correlation analysis between uric acid in the organs and gene expression (measured by FPKM value) was made. Serum uric acid (SUA) in patients with breast cancer or with breast benign tumor was assayed when the diagnosis was made, and SUA in patients with breast cancer was also assayed just after chemotherapy. There were 1937 mRNAs whose expression level significantly correlated with the level of uric acid, and most of which were associated with purine or nucleoside metabolism, cellular metabolism, cell cycles, and cell death pathways. Further analysis showed that the level of uric acid was highly correlated with cell death rather than cell viability. The level of SUA in patients with breast cancer was higher than that in patients with breast benign tumor, and the SUA increased after chemotherapy. All the results suggested that uric acid was mainly synthesized from local nucleosides degraded from dead cells, and uric acid could be an important biomarker for cell death rather than an antioxidant for neural protection.
Chinese Herbal Formula Feilin Vaginal Gel Prevents the Cervicitis in Mouse Model
Authors: Mao Xin , Zhao Ronghua , Yao Rongmei , Guo Shanshan , Bao Lei , Gao Yingjie , Sun Jing , Bao Yanyan , Shi Yujing , Cui Xiaolan
Published: January 2019

Cervicitis is a common sexually transmitted disease. In recent years, the abuse of antibiotic in the treatment of cervicitis results in the emergence of antibiotic-resistant bacteria; alternative strategies are needed to be developed. In this research, we investigated the effects of Feilin Vaginal Gel (FVG), a Chinese herbal formula, on the treatment of cervicitis. Two cervicitis models were optimized using BALB/c mouse; onein vitromodel was established in HeLa cells. InChlamydia trachomatis-induced cervicitis model, the high level of bacterial loads, the inflammation in tissue, and the cytokines in serum could be observed. With the administration of FVG, the bacterial loads in cervical mucus and cervix tissue could be significantly inhibited in dose-dependent manners. The pathological injury of cervix and vagina, as well as the levels of IL-2, IL-17, and MCP-1 in serum, could be mitigated by FVG. FVG reduced the number of inclusion induced byC. trachomatisin HeLa cells. In addition, the histological damage inEscherichia coliandStaphylococcus aureus-induced cervicitis model could be reduced by FVG. These results suggest that FVG is capable of treating cervicitis through the inhibition of pathogens and the regulation of host immune responses. FVG may contribute as an alternative agent for the treatment of cervicitis.
Preservation of Meat Products with Bacteriocins Produced by Lactic Acid Bacteria Isolated from Meat
Authors: da Costa Roger J. , Voloski Flávia L. S. , Mondadori Rafael G. , Duval Eduarda H. , Fiorentini Ângela M.
Published: January 2019

Bacteriocins are ribosomal-synthesized antimicrobial peptides that inhibit the growing of pathogenic and/or deteriorating bacteria. The most studied bacteriocin-producing microorganisms are lactic acid bacteria (LAB), as they have great potential application in food biopreservation, since the majority have GRAS (Generally Recognized as Safe) status. The LAB-producing bacteriocins and/or bacteriocins produced by these bacteria have been widely studied, with the emphasis on those derived from milk and dairy products. On the other hand, isolates from meat and meat products are less studied. The objective of this review is to address the main characteristics, classification, and mechanism of action of bacteriocins and their use in food, to highlight studies on the isolation of LAB with bacteriocinogenic potential from meat and meat products and also to characterize, purify, and apply these bacteriocins in meat products. In summary, most of the microorganisms studied areLactococcus,Enterococcus,Pediococcus, andLactobacillus, which produce bacteriocins such as nisin, enterocin, pediocin, pentocin, and sakacin, many with the potential for use in food biopreservation.
High Lyso-Gb3 Plasma Levels Associated with Decreased miR-29 and miR-200 Urinary Excretion in Young Non-Albuminuric Male Patient with Classic Fabry Disease
Authors: Jaurretche Sebastián , Perez Germán R. , Venera Graciela
Published: January 2019

Renal involvement is associated with a greater morbidity and mortality in Fabry disease. Pathological albuminuria, the first Fabry nephropathy clinical manifestation, can occur from early childhood, although histological lesions such as tubulo-interstitial fibrosis and glomerulosclerosis are present or may precede the onset of pathological albuminuria. In renal cells, exposure to Lyso-Gb3 is correlated with increased expression of Transforming Growth Factor-βeta (TGF-β). miR-21, miR-192, and miR-433 that promote fibrosis are activated by TGF-β, and miR-29 and miR-200 that suppress fibrosis are inhibited by TGF-β. A 23-year-old male was diagnosed with FD.αGalA decreased enzyme activity: 0.1 nmol/hour/liter; genotype: [c.317T>G (p.L106R)]; GFR: 104.4 mL/min/m2; urinary albumin excretion: 6.00 mg/day; plasma Lyso-Gb3: 124.5 nmol/L. A decrease urinary excretion of miR-29 and miR-200 was found (p <0.005) compared to controls. In addition to its usefulness as a phenotype marker, Lyso-Gb3 has been proposed as an indicator of therapeutic response. We detect an association of high Lyso-Gb3 plasma values with decreased urinary excretion of miRNAs with known antifibrotic effect (miR-29 and miR-200). Although the present work is a case report, it could be hypothesized that one of the harmful Lyso-Gb3 effects could be the miRNAs regulation through changes in TGF-βexpression.
Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer
Authors: Blessin Niclas C. , Simon Ronald , Kluth Martina , Fischer Kristine , Hube-Magg Claudia , Li Wenchao , Makrypidi-Fraune Georgia , Wellge Björn , Mandelkow Tim , Debatin Nicolaus F. , Höflmayer Doris , Lennartz Maximilian , Sauter Guido , Izbicki Jakob R. , Minner Sarah , Büscheck Franziska , Uhlig Ria , Dum David , Krech Till , Luebke Andreas M. , Wittmer Corinna , Jacobsen Frank , Burandt Eike-Christian , Steurer Stefan , Wilczak Waldemar , Hinsch Andrea
Published: January 2019

TIGIT is an inhibitory immune checkpoint receptor and a putative target for novel immune therapies. Here, we analysed two different types of tissue microarrays of healthy lymphatic and various inflamed tissues, colorectal and lung cancers, as well as >1700 tumour samples from 86 different tumour entities for TIGIT and/or PD-1 by bright field and/or multiplex fluorescence immunohistochemistry. TIGIT was detected in CD8+ cytotoxic T cells, CD4+ T helper cells, FOXP3+ regulatory T cells, and NK cells, but not in CD11c+ dendritic cells, CD68+ macrophages, and CD20+ B lymphocytes. TIGIT expression paralleled that of PD-1. More than 70% of TIGIT+ cells were PD-1+, and more than 90% of the PD-1+ cells were TIGIT+. Expression varied between different tissue compartments. TIGIT expression in tonsil gradually increased from the interfollicular area over the marginal/mantle zone to the germinal centre in all T cell subtypes. In inflammatory diseases, the strongest expression of TIGIT/PD-1 was found in Hashimoto thyroiditis. TIGIT+ lymphocytes were seen in all 86 different tumour entities with considerable high variability of TIGIT positivity within and between different cancer entities. Particularly, high densities of TIGIT+ lymphocytes were, for example, seen in squamous cell cancers of various origins. In summary, the variable expression levels of TIGIT and PD-1 in cell types and tissue compartments illustrate the high complexity of immune microenvironments. The high frequency of TIGIT (and PD-1) expressing lymphocytes in cancers highlights considerable opportunities for cotargeting with checkpoint inhibitors.
Postprandial Glycaemic and Insulinaemic Responses after Consumption of Activated Wheat and Triticale Grain Flakes
Authors: Meija Laila , Havensone Guna , Lejnieks Aivars
Published: January 2019

Increasing evidence shows that whole grain consumption is protective against metabolic disorders. Protective bioactive substances of whole grains include fibre and antioxidants. Activation of grains can increase the amount of phenolic compounds and their bioavailability, but there is little evidence about their effect on glycaemic and insulinemic responses. Therefore, the aim of this study was to investigate glycaemic and insulinemic responses after consumption of flakes made from activated wheat and activated triticale grains. Eighteen healthy subjects (7 men and 11 women) were given activated wheat or activated triticale flakes. As a reference, a standard glucose solution was used. Plasma glucose and serum insulin were measured during 120 minutes. Both, activated wheat and activated triticale flakes, show improved glycaemic profile, inducing a lower and more stable glycaemic response. However, statistically significant differences in insulin response were found only in the group who have taken activated triticale flakes and not in the group who have taken activated wheat flakes. Activated triticale flakes induced lower insulin response in all postprandial phases and a more stable concentration of insulin. Thus, activated triticale flakes could be beneficial for the prevention and treatment of metabolic disorders.
Optimization of Experimental Settings for the Assessment of Reactive Oxygen Species Production by Human Blood
Authors: Soares Tânia , Rodrigues Daniela , Sarraguça Mafalda , Rocha Sílvia , Lima José L. F. C. , Ribeiro Daniela , Fernandes Eduarda , Freitas Marisa
Published: January 2019

The purpose of an experimental design is to improve the productivity of experimentation. It is an efficient procedure for planning experiments, so the data obtained can be analyzed to yield a valid and objective conclusion. This approach has been used as an important tool in the optimization of different analytical approaches. A D-optimal experimental design was used here, for the first time, to optimize the experimental conditions for the detection of reactive oxygen species (ROS) produced by human blood from healthy donors, a biological matrix that better resembles the physiologic environment, following stimulation by a potent inflammatory mediator, phorbol-12-myristate-13-acetate (PMA). For that purpose, different fluorescent probes were used, as 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA), 2-[6-(4′-amino)-phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (APF), and 10-acetyl-3,7-dihydroxyphenoxazine (amplex red). The variables tested were the human blood dilution, and the fluorescent probe and PMA concentrations. The experiments were evaluated using the Response Surface Methodology and the method was validated using specific compounds. This model allowed the search for optimal conditions for a set of responses simultaneously, enabling, from a small number of experiments, the evaluation of the interaction between the variables under study. Moreover, a cellular model was implemented and optimized to detect the production of ROS using a yet nonexplored matrix, which is human blood.
Preparation and Heavy Metal Ions Chelating Properties of Multifunctional Polymer-Grafted Silica Hybrid Materials
Authors: Sartore Luciana , Dey Kamol
Published: January 2019

In this research work, novel hybrid materials based on multifunctional polymers and silica were developed and investigated in view of possible employment as sorbents for removal of heavy metal ions from water in presence of various ions. Organic-inorganic hybrid materials were prepared by covalent bonding of vinyl-terminated polyamidoamine (PAA) onto aminated silica particles. Two series of polyamidoamine-grafted silica, differing in the PAA chemical structure, were synthesized, and their heavy metal ions chelating properties were investigated. Column adsorption procedure for Cu, Zn, and Ni in aqueous solution was successfully established. Moreover, the adsorption behaviour of the materials was evaluated in different ionic strength solutions as well as in distilled and natural water. Organic-inorganic hybrid materials exhibited excellent chelating properties and selectivity for different metal ions. The hybrid columns showed exceptional eluting and regenerating property using diluted hydrochloric acid solution as eluent. In particular, the hybrid materials containing more carboxy groups possessed superior adsorption ability, reusability, and stability. The consecutive adsorption-desorption experiments exhibited that this material could be reused more than 20 cycles without almost any loss of adsorption capability. These new organic-inorganic sorbents appear very promising as an effective solid-phase extraction material for the selective preconcentration or removing of heavy metal ions from the environment.
The Effects of Diabetic Duration on Lacrimal Functional Unit in Patients with Type II Diabetes
Authors: Zeng Xiaoyu , Lv Ying , Gu Zhongxiu , Jia Zhe , Zhang Chen , Lu Xiaoxiao , Chu Chenchen , Gao Yichen , Nie Yu , Wang Yanxia , Zhang Yan , Zhao Shaozhen
Published: January 2019

Purpose. To observe ocular surface changes in Type II diabetic patients with different disease durations and to understand the correlations between clinical parameters and diabetic durations. Methods. In this cross-sectional, prospective study, 51 healthy controls and 91 patients with Type II diabetes were enrolled. The diabetics were divided into 3 subgroups according to the disease duration, including duration <10 y group, 10 to 20 y group, and ≥21 y group. All subjects underwent clinical ocular examinations, including lipid layer thickness (LLT), blinking rate, tear meniscus height (TMH), noninvasive tear film break-up time (NI-BUT), meibography, superficial punctate keratopathy (SPK) scoring, corneal sensitivity, and Schirmer I test. They were also evaluated using the standard patient evaluation of eye dryness (SPEED) questionnaire. Results. SPEED score, meiboscore, SPK score, LLT, Schirmer I test, and corneal sensitivity differed significantly between the diabetic and healthy control groups. Further, SPEED score, Schirmer I test, corneal sensitivity, meiboscore, and blink rate significantly differed among the 3 diabetic subgroups and the control group. In diabetics, the SPEED score correlated with the SPK score, blink rate, TMH, and LLT; NI-BUT with TMH, LLT, and blink rate; TMH with the SPK score; Schirmer I test with the SPK score; and corneal sensitivity with the meiboscore. More importantly, the Schirmer I test, corneal sensitivity, and SPEED score negatively correlated with diabetic duration. Conclusion. Diabetic duration is an important factor that affects functions of the lacrimal functional unit in patients with Type II diabetes. The trends of changes in the ocular parameters vary along the course of diabetes.
Tsallis Holographic Dark Energy with Granda-Oliveros Scale in (n+1)-Dimensional FRW Universe
Authors: Aly Ayman A.
Published: January 2019

Based on Tsallis holographic dark energy model recently proposed by using the general model of the Tsallis entropy expression, we reconstruct cosmographic parameters, q,j,κ,l, and we study their evolution in spatially flat (n+1)-dimensional Friedmann-Robertson-Walker universe using Granda-Oliveros scale. Our results show that the universe is in an accelerating expansion mode described by phantom-like behavior. We go further and study the state finder operators and the Om diagnostic to understand the behavior of our model. The stability of the system is also studied by using the square of speed of sound showing that our model is stable over the low range of red-shift considered. The results indicate that the entropy formalism will play an important role in understanding the dynamics of our universe.
In SilicoGenome-Wide Analysis of the ATP-Binding Cassette Transporter Gene Family in Soybean (Glycine maxL.) and Their Expression Profiling
Authors: Mishra Awdhesh Kumar , Choi Jinhee , Rabbee Muhammad Fazle , Baek Kwang-Hyun
Published: January 2019

ATP-binding cassette (ABC) transporters constitute one of the largest gene families in all living organisms, most of which mediate transport across biological membranes by hydrolyzing ATP. However, detailed studies of ABC transporter genes in the important oil crop, soybean, are still lacking. In the present study, we carried out genome-wide identification and phylogenetic and transcriptional analyses of the ABC gene family inG.max. A total of 261G.maxABC (GmABCs) genes were identified and unevenly localized onto 20 chromosomes. Referring to protein-domain orientation and phylogeny, the GmABC family could be classified into eight (ABCA-ABCG and ABCI) subfamilies and ABCG were the most abundantly present. Further, investigation of whole genome duplication (WGD) signifies the role of segmental duplication in the expansion of the ABC transporter gene family in soybean. The Ka/Ks ratio indicates that several duplicated genes are governed by intense purifying selection during evolution. In addition,in silicoexpression analysis based on RNA-sequence using publicly available database revealed that ABC transporters are differentially expressed in tissues and developmental stages and in dehydration. Overall, we provide an extensive overview of the GmABC transporter gene family and it promises the primary basis for the study in development and response to dehydration tolerance.
Epiretinal Membrane Surgery in Daily Clinical Practice: Results of a Proposed Management Scheme
Authors: Pareja Jesús , Coronado Alba , Contreras Inés
Published: January 2019

Purpose. To report the results of the epiretinal membrane (ERM) management guidelines followed in our center. Methods. Patients with ERM seen between 2014 and 2015, with ≥2 years follow-up or who had undergone ERM surgery, were included. Corrected visual acuity (VA), lens status, and ERM configuration were recorded at each visit. Our guidelines for ERM are if VA is ≥20/30, observation is recommended unless there is moderate/intense metamorphopsia. Vitrectomy is recommended during follow-up if there is a drop >one line in VA with changes in ERM configuration. If VA at diagnosis is <20/30, vitrectomy is recommended. If visual loss is thought to be due to cataract, phacoemulsification is performed first and visual status reevaluated. Results. Ninety-nine eyes of 94 patients were included; 52 eyes underwent vitrectomy, and 47 eyes were monitored. From eyes with VA at diagnosis <20/30 (41 eyes), 8 eyes underwent isolated phacoemulsification: VA improved to ≥20/30. Vitrectomy was recommended but refused by 4 patients. The other 29 eyes underwent vitrectomy. Of the 58 eyes with VA at diagnosis ≥20/30, 5 underwent surgery due to metamorphopsia. Eighteen eyes underwent vitrectomy during follow-up. VA improved a mean of 0.13 logMAR (SD 0.30) after vitrectomy. There were no differences in mean VA improvement between eyes that underwent vitrectomy within six months of diagnosis (0.24, SD 0.32) and those that underwent surgery more than six months after diagnosis (mean 0.17, SD 0.17), p=0.106. Three eyes developed postsurgical complications with visual loss: persistent macular edema in one eye, two consecutive retinal detachments in one eye, and a central visual defect in another eye. At the end of follow-up, VA was similar in the observation group (0.14, SD 0.14) and in the vitrectomy group (0.16, SD 0.28), p=0.528. Conclusions. Our proposed guidelines lead to visual preservation in most patients while limiting surgery and its possible complications.
Mediators of Inflammation in Topical Therapy of Skin Cancers
Authors: Voiculescu Vlad Mihai , Lisievici Cristina Victoria , Lupu Mihai , Vajaitu Cristina , Draghici Carmen Cristina , Popa Alexandra Victoria , Solomon Iulia , Sebe Teona Ioana , Constantin Maria Magdalena , Caruntu Constantin
Published: January 2019

Taking into consideration that the immune system plays a very important role in the development of melanoma and non-melanoma skin cancers, which have a high prevalence in immunosuppressed patients and after prolonged ultraviolet radiation, the interest in developing novel therapies, in particular targeting the inflammation in cancer, has increased in the past years. The latest data suggest that therapies such as imiquimod (IMQ), ingenol mebutate (IM), 5-fluorouracil (5-FU), retinoids, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been used with success in the topical treatment of some cancers. Herein, we review the topical treatment targeting the inflammation in skin cancer and the mechanisms involved in these processes. Currently, various associations have shown a superior success rate than monotherapy, such as systemic acitretin and topical IMQ, topical 5-FU with tretinoin cream, or IMQ with checkpoint inhibitor cytotoxic T lymphocyte antigen 4. Novel therapies targeting Toll-like receptor-7 (TLR-7) with higher selectivity than IMQ are also of great interest.
Corrosion Study of Aluminum Alloy 3303 in Water-Ethylene Glycol Mixture: Effect of Inhibitors and Thermal Shocking
Authors: Asadikiya Mohammad , Zhong Yu , Ghorbani Mohammad
Published: January 2019

Three types of corrosion inhibitors consisting of sodium diphosphate (Na2H2P2O7), sodium benzoate (NaC7H5O2), and sodium tetraborate (Na2B4O7) were evaluated to analyze their effectiveness to inhibit the aluminum alloy 3303 (UNS A93303) against corrosion, in water-ethylene glycol (C2H6O2) mixture. Potentiodynamic polarization tests were carried out to study the effect of each chemical. The temperature of solutions was 88°C and the aluminum samples were coupled with five other metals consisting of mild steel, stainless steel, brass, copper, and solder to include the effect of galvanic corrosion. The results showed that sodium diphosphate can effectively protect the aluminum alloy 3303 in comparison with two other chemicals. The effect of thermal shocking on the corrosivity of water-ethylene glycol solution was also investigated. It was indicated that the corrosivity of water-ethylene glycol solution increases because of thermal shocking, which oxidizes the aqueous ethylene glycol. The corrosion rate of aluminum alloy 3303 coupled with the five metals in thermal shocked water-ethylene glycol solution is 142 mpy, while it is 94 mpy in fresh water-ethylene glycol solution.