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Olivares Garita, Cinthya, and Jorge Altamirano Alvarado. "Folktales and Short Stories to Blend Culture and Language Competence." LETRAS, no. 68 (July 6, 2020): 107–41. http://dx.doi.org/10.15359/rl.2-68.5.
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 The aim of this research is to study the use of literature-based cultural material to reinforce speaking and writing skills by using folktales (general culture) and short stories (home culture) in oral and written expression in the English Teaching major. The analysis of a questionnaire for teachers and students indicates that those texts are rarely used to strengthen the productive skills. Based on this, a proposal has been devised to blend world and home culture with language competence to develop written and oral activities in the classroom.
 
 
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CHIKAI, Manabu, Naomi SHIRAI, and Hitoshi MIYAKE. "1302 Reexamination of "Touch Blend" for Haptic Expression." Proceedings of Conference of Hokuriku-Shinetsu Branch 2011.48 (2011): 409–10. http://dx.doi.org/10.1299/jsmehs.2011.48.409.
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Biagioli, Michele, Daniela Capobianco, Adriana Carino, et al. "Divergent Effectiveness of Multispecies Probiotic Preparations on Intestinal Microbiota Structure Depends on Metabolic Properties." Nutrients 11, no. 2 (2019): 325. http://dx.doi.org/10.3390/nu11020325.
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A growing body of evidence suggests that probiotic functionality is not accurately predicted by their taxonomy. Here, we have set up a study to investigate the effectiveness of two probiotic formulations containing a blend of seven bacterial species in modulating intestinal inflammation in two rodent models of colitis, induced by treating mice with 2,4,6-Trinitrobenzenesulfonic acid (TNBS) or dextran sodium sulfate (DSS). Despite the taxonomy of the bacterial species in the two probiotic formulations being similar, only one preparation (Blend 2-Vivomixx) effectively attenuated the development of colitis in both models. In the TNBS model of colitis, Blend 2 reduced the expression of pro-inflammatory genes while increasing the production of anti-inflammatory cytokines, promoting the expansion M2 macrophages and the formation of IL-10-producing Treg cells in the colon’s lamina propria. In the DSS model of colitis, disease attenuation and Treg formation was observed only in mice administered with Blend 2, and this effect was associated with intestinal microbiota remodeling and increased formation of lactate, butyrate, and propionate. None of these effects were observed in mice administered with Blend 1 (VSL#3). In summary, we have shown that two probiotic mixtures obtained by combining taxonomically similar species produced with different manufacturing methods exert divergent effects in mouse models of colitis.
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Lu, Jihong, Lilan Jin, Lu Deng, et al. "Primary Evaluation of Anti-Inflammatory Effect of a Botanical Extract-Based Blend in a Haze Infected Cell Model." Current Developments in Nutrition 4, Supplement_2 (2020): 432. http://dx.doi.org/10.1093/cdn/nzaa045_065.
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Abstract Objectives Exposure to air pollution has been associated with throat discomfort, cough, pulmonary disease, and even lung cancer. We developed a botanical extract-based blend with the goal of ameliorating some of the adverse effects of airborne pollutants. This blend consisted of broccoli seed (BS, Brasssica oleracea) extract, Luo Han Guo (LH G, Siraitia grovenorii) extract, and Honeysuckle Flower Bud (HFB, Lonicera japonica) extract. BS extract is rich in Sulforaphane glucosinolate and is reported to promote healthy inflammatory balance as well as to regulate oxidative stress and DNA-damaging substances. LHG has been used as a traditional medicine for the treatment of pharyngitis, pharyngeal pain, as well as an antitussive remedy in China. HFB is a traditional herbal medicine widely used in East Asia as an anti-inflammatory and anti-oxidative agent. Methods In order to evaluate the effectiveness of this putative airborne pollutant defense blend, human alveolar basal epithelial cells in adenocarcinoma (A549) were treated by exposing total culture medium (TCMed, to 0.02 mg/mL of haze particles (HP). Gene expression of inflammatory factors IL-1β, IL-8, TNF-α, INF-γ, and cell tight junction proteins were detected by qPCR at 0.5, 1, 2, and 6H when treated with 0.02 mg/mL HP TCMed alone (group H), 0.02 mg/mL HP TCMed + 5 mg/mL of LHG + HFB blend (LHG: HFB 1:10) +0.01 mg/mL of L-sulforaphane (group HT). Results We found that gene expression of IL-1β, IL-8 and TNF-α were significantly decreased in HT at 1, 2, and 6 H treatment as compared to the F group. Gene expression of tight junction protein OCLN and ZO-1, which is a scaffolding protein, were significantly increased in HT as compared to the F group. Conclusions This botanical extract blend regulates inflammatory factors and balances cell transmembrane stability in a primary cell haze infection model and therefore may be useful as a preventive formulation to help alleviate the adverse effects of airborne pollutants. Funding Sources Nu Skin Enterprises.
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Reidy, P. T., D. K. Walker, J. M. Dickinson, et al. "Soy-dairy protein blend and whey protein ingestion after resistance exercise increases amino acid transport and transporter expression in human skeletal muscle." Journal of Applied Physiology 116, no. 11 (2014): 1353–64. http://dx.doi.org/10.1152/japplphysiol.01093.2013.
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Increasing amino acid availability (via infusion or ingestion) at rest or postexercise enhances amino acid transport into human skeletal muscle. It is unknown whether alterations in amino acid availability, from ingesting different dietary proteins, can enhance amino acid transport rates and amino acid transporter (AAT) mRNA expression. We hypothesized that the prolonged hyperaminoacidemia from ingesting a blend of proteins with different digestion rates postexercise would enhance amino acid transport into muscle and AAT expression compared with the ingestion of a rapidly digested protein. In a double-blind, randomized clinical trial, we studied 16 young adults at rest and after acute resistance exercise coupled with postexercise (1 h) ingestion of either a (soy-dairy) protein blend or whey protein. Phenylalanine net balance and transport rate into skeletal muscle were measured using stable isotopic methods in combination with femoral arteriovenous blood sampling and muscle biopsies obtained at rest and 3 and 5 h postexercise. Phenylalanine transport into muscle and mRNA expression of select AATs [system L amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, system A amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, cationic amino acid transporter 1/SLC7A1] increased to a similar extent in both groups ( P < 0.05). However, the ingestion of the protein blend resulted in a prolonged and positive net phenylalanine balance during postexercise recovery compared with whey protein ( P < 0.05). Postexercise myofibrillar protein synthesis increased similarly between groups. We conclude that, while both protein sources enhanced postexercise AAT expression, transport into muscle, and myofibrillar protein synthesis, postexercise ingestion of a protein blend results in a slightly prolonged net amino acid balance across the leg compared with whey protein.
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Groot, Astrid T., Michiel van Wijk, Ernesto Villacis-Perez, et al. "Within-population variability in a moth sex pheromone blend, part 2: selection towards fixation." Royal Society Open Science 6, no. 3 (2019): 182050. http://dx.doi.org/10.1098/rsos.182050.
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To understand how variation in sexual communication systems evolves, the genetic architecture underlying sexual signals and responses needs to be identified. Especially in animals where mating signals are important for mate recognition, and signals and responses are governed by independently assorting genes, it is difficult to envision how signals and preferences can (co)evolve. Moths are a prime example of such animals. In the noctuid moth Heliothis virescens , we found within-population variation in the female pheromone. In previous selection experiments followed by quantitative trait locus (QTL) analysis and expression analysis of candidate desaturase genes, we developed a model involving a trans -acting repressor of the delta-11-desaturase. In our current study with new selection lines, we fixed the most extreme phenotype and found a single underlying mutation: a premature stop codon in the first coding exon of delta-11-desaturase, which we could trace back to its origin in the laboratory. Interestingly, we found no pleiotropic effects of this knock-out mutation on the male physiological or behavioural response, or on growth or fertility. This finding is in contrast to Drosophila melanogaster , where a single desaturase gene affects both female pheromone production and male behavioural response, but similar to other Lepidoptera where these traits are under independent genetic control. To our knowledge, this is the first time that a single point mutation has been identified that underlies the phenotypic variation in the pheromone signal of a moth.
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Haskey, N., J. Ye, J. A. Barnett, et al. "A44 FATTY ACID COMPOSITION OF THE MEDITERRANEAN DIET PROTECTS AGAINST SPONTANEOUS COLITIS IN THE MUCIN-2 DEFICIENT MURINE MODEL." Journal of the Canadian Association of Gastroenterology 4, Supplement_1 (2021): 292–94. http://dx.doi.org/10.1093/jcag/gwab002.042.
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Abstract Background A Mediterranean diet (MD) has been proven efficacious in reducing inflammation in many chronic conditions, mediated by the interaction between diet, the gut microbiota and the immune system. The role of the MD as a dietary management strategy in the management of colitis requires further elucidation. While high fat diets have been shown to result in dysbiosis, our lab has clarified that the type of fat, not total calories derived from fat, predict gut dysbiosis and immunity in murine models of colitis. The n-6 polyunsaturated fatty acids (PUFA) promote colitis, however monounsaturated fatty acids (MUFA) protect against colitis. We hypothesize that a blend of fats, similar to the MD (high MUFA, low n-6 PUFA) will promote gut health beneficial to colitis. Aims Using a murine model of chronic intestinal inflammation, the aim of this study was to investigate the effects of dietary fatty acids on colitis by studying dietary fats in isolation from each other, as well as in a fatty acid profile similar to the blend contained in the MD. Methods Mice lacking the mucin 2 gene (Muc 2-/-) were weaned on to a 9-week, high fat (41%), isocaloric, isonitrogenous diet where the fat was derived from corn oil, olive oil, milk fat or a MD fat blend (28% MUFA, 8% SFA, 4% n-6 PUFA, 1% n-3 PUFA). The MD fat blend mimicked the fat profile consumed in the human diet. Disease activity, colon histology, cytokines (serum and colonic expression), cecal short chain fatty acids, intestinal permeability, glucose tolerance and gut microbiota (16S rRNA) were analyzed. Results Muc 2-/- fed the MD were protected from developing the most severe form of colitis, showing significantly lower disease activity and the absence of rectal prolapse. Histological damage was more severe in the corn oil and milk fat groups which coincided with an increase in infiltrating inflammatory cells and increased mucosal ulcerations. MD and milk fat diets exhibited enhanced intestinal permeability, glucose tolerance, intestinal alkaline phosphatase compared to the corn oil diet. Lower colonic mRNA levels of pro-inflammatory RELM-ß and IL-6 were also seen in the MD and MF diet in comparison to corn oil diet with the milk fat eliciting unique protective immune responses as evidenced by increased expression of IL-22 and Reg3-γ. Differences in alpha-diversity were seen between the MD and milk fat diets, beta-diversity revealed differences in taxa between diet groups. Conclusions The fatty acid profile of the MD protects against the development of spontaneous colitis in the Muc2-/- mouse model. In summary, not all dietary fats aggravate colitis, and some may be beneficial during colitis. A diet low in n-6 PUFA and high in MUFA is recommended. Funding Agencies CCCCFDR
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Toschi, Andrea, Barbara Rossi, Benedetta Tugnoli, Andrea Piva, and Ester Grilli. "Nature-Identical Compounds and Organic Acids Ameliorate and Prevent the Damages Induced by an Inflammatory Challenge in Caco-2 Cell Culture." Molecules 25, no. 18 (2020): 4296. http://dx.doi.org/10.3390/molecules25184296.
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Bioactive compounds, such as organic acids (OA) and nature-identical compounds (NIC), can exert a role in the protection of intestinal mucosa functionality due to their biological properties. The aim of this study was to understand the role of 2 OA (citric and sorbic acid) and 2 NIC (thymol and vanillin), alone or combined in a blend (OA + NIC), on intestinal barrier functionality, either during homeostatic condition or during an inflammatory challenge performed with pro-inflammatory cytokines and lipopolysaccharides (LPS). The study was performed on the human epithelial cell line Caco-2, a well-known model of the intestinal epithelial barrier. The results showed how OA and NIC alone can improve transepithelial electrical resistance (TEER) and mRNA levels of tight junction (TJ) components, but OA + NIC showed stronger efficacy compared to the single molecules. When an inflammatory challenge occurred, OA + NIC blend was able both to ameliorate, and prevent, damage caused by the pro-inflammatory stimulus, reducing or preventing the drop in TEER and improving the TJ mRNA expression. The data support the role of OA + NIC in modulating gut barrier functionality and reducing the negative effects of inflammation in intestinal epithelial cells, thereby supporting the gut barrier functionality.
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Troche, Catalina, Susan D. Eicher, and Todd J. Applegate. "The influence of dietary zinc source and coccidial vaccine exposure on intracellular zinc homeostasis and immune status in broiler chickens." British Journal of Nutrition 114, no. 2 (2015): 202–12. http://dx.doi.org/10.1017/s0007114515001592.
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Coccidia are protozoal parasites which compromise mucosal integrity of the intestine, potentiating poultry morbidity. The host's Zn status influences the course of infection. Therefore, two experiments were designed to determine how supplemental Zn regimens impacted jejunal and caecal immune status and Zn transporter expression. Coccivac®-B was administered weekly at ten times the recommended dose as a mild coccidial challenge (10CV). Zn was provided through a basal diet, supplemental zinc sulfate (ZnSO4), or a supplemental 1:1 blend of ZnSO4 and Availa®-Zn (Blend). Mucosal jejunum (Expt 1) and caecal tonsils (Expt 2) were evaluated for intracellular Zn concentrations and phagocytic capacity. Messenger expression of Zn transporters ZnT5, ZnT7, Zip9 and Zip13 were investigated to determine Zn trafficking. With 10CV, phagocytic capacity was decreased in jejunal cells by 2 %. In the caecal tonsils, however, phagocytic capacity increased with challenge, with the magnitude of increase being more pronounced with higher dietary Zn (10CV × Zn interaction; P= 0·04). Intracellular Zn within caecal tonsils was found significantly reduced with 10CV (27 %, P= 0·0001). 10CV also resulted in an overall increase in the ratio of Zip:ZnT transporters. With the exception of Zip13 transporter expression, dietary Zn source had little impact on any of the measured cellular parameters. Thus, intestinal mucosal tissues had reductions in intracellular free Zn during coccidial challenge, which was coupled with an upregulation of measured Zip transporters. This suggests that under coccidial challenge, intestinal cells attempt to compensate for the drop in intracellular Zn.
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Liland, Nina S., Marit Espe, Grethe Rosenlund, et al. "High levels of dietary phytosterols affect lipid metabolism and increase liver and plasma TAG in Atlantic salmon (Salmo salarL.)." British Journal of Nutrition 110, no. 11 (2013): 1958–67. http://dx.doi.org/10.1017/s0007114513001347.
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Replacing dietary fishmeal (FM) and fish oil (FO) with plant ingredients in Atlantic salmon (Salmo salarL.) diets decreases dietary cholesterol and introduces phytosterols. The aim of the present study was to assess the effect of dietary sterol composition on cholesterol metabolism in Atlantic salmon. For this purpose, two dietary trials were performed, in which Atlantic salmon were fed either 100 % FM and FO (FM-FO) diet or one of the three diets with either high (80 %) or medium (40 %) plant protein (PP) and a high (70 %) or medium (35 %) vegetable oil (VO) blend (trial 1); or 70 % PP with either 100 % FO or 80 % of the FO replaced with olive, rapeseed or soyabean oil (trial 2). Replacing ≥ 70 % of FM with PP and ≥ 70 % of FO with either a VO blend or rapeseed oil increased plasma and liver TAG concentrations. These diets contained high levels of phytosterols and low levels of cholesterol. Fish fed low-cholesterol diets, but with less phytosterols, exhibited an increased expression of genes encoding proteins involved in cholesterol uptake and synthesis. The expression of these genes was, however, partially inhibited in rapeseed oil-fed fish possibly due to the high dietary and tissue phytosterol:cholesterol ratio. Atlantic salmon tissue and plasma cholesterol concentrations were maintained stable independent of the dietary sterol content.
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Tian and Piao. "Essential Oil Blend Could Decrease Diarrhea Prevalence by Improving Antioxidative Capability for Weaned Pigs." Animals 9, no. 10 (2019): 847. http://dx.doi.org/10.3390/ani9100847.
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Finding an alternative to in-feed antibiotics is important because of increasing contemporary concern regarding drug residues and the development of drug-resistant bacteria. The purpose of this study was to test the hypothesis that essential oils added to the feed would decrease diarrhea prevalence in post-weaned pigs. Ninety weaned piglets (initial body weight (BW): 8.1 ± 1.4 kg) were randomly assigned to one of three dietary diets: (1) a control diet (CON, the basal diet without antibiotics), (2) an antibiotic diet (AB, CON supplemented with colistin sulfate, 20 mg/kg and bacitracin zinc, 40 mg/kg), or (3) an essential oil diet (EO, CON supplemented with an essential oil blend 100 mg/kg) in a completely randomized block design for a 28-day period. The results revealed that AB and EO improved the average daily gain of the piglets from day (d) 15 to 28 (p < 0.05). The diarrhea prevalence in piglets fed AB and EO was lower than that of piglets fed CON (p < 0.05). There was no significant difference in the growth performance or diarrhea prevalence between the AB and EO treatments. Nutrient digestibility was measured at d 28. Compared with CON, EO increased the apparent total tract digestibility of gross energy and crude protein (p < 0.05). Villus height in the duodenum and the ratio of villus height to crypt depth in the jejunum for piglets fed AB and EO was greater than those for piglets fed CON (p < 0.05). The essential oil blend improved the superoxide dismutase (SOD) and catalase (CAT) activities and total antioxidant capacity (T-AOC), but decreased the 8-hydroxy deoxyguanosine content in serum on d 14 (p < 0.05). Decreased malondialdehyde (MDA) and protein carbonyl content were observed on d 28 in comparison with CON (p < 0.05). The mucosa in the jejunum of pigs fed EO had greater T-AOC, SOD levels, and glutathione peroxidase (GSH-Px) activities than that of pigs fed CON (p < 0.05). Pigs fed EO and AB had greater GSH-Px activity in the liver tissue than pigs fed CON (p < 0.05). Not only did jejunal and ileal mucosa have EO upregulated SOD1 mRNA expression (p < 0.05), this was also the case in liver tissue. GPx1 expression in the ileal mucosa and GPx4 expression in the liver tissue were higher for pigs fed EO when compared to those fed CON (p < 0.05). Collectively, a dietary essential oil blend supplementation, which has natural antimicrobial properties, could enhance growth performance and decrease diarrhea prevalence in weaned pigs through increases in antioxidative capacity.
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RIVIÈRE, Stéphane, Audrey LARTIGUE, Brigitte QUENNEDEY, et al. "A pheromone-binding protein from the cockroach Leucophaea maderae: cloning, expression and pheromone binding." Biochemical Journal 371, no. 2 (2003): 573–79. http://dx.doi.org/10.1042/bj20021877.
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Odorant-binding proteins (OBPs) are thought to transport volatile compounds from air to their receptors through the sensillary lymph. In this protein family, the subgroup of pheromone-binding proteins (PBPs) is specifically tuned to the perception of the sexual pheromone. To date, the description of OBPs has been restricted to Endopterygota and Paraneoptera. Their expression in Orthopteroid has been hypothesized, but no evidence of OBP has been produced in this assemblage to date. In the present study, we describe the first OBP from a Dictyopteran insect that belongs to the cockroach Leucophaea maderae. The PBP of L. maderae (PBPLma) shares all the hallmarks of the OBP family and is expressed specifically in the female adult antennae, the sex that perceives the sexual pheromone. The affinity of the recombinant PBPLma produced in the Escherichia coli periplasm for the pheromonal compounds has been tested by displacement of a fluorophore, 8-anilino-1-naphtalenesulphonic acid (ANS). Our results suggest that two chemically close compounds of the pheromonal blend (3-hydroxy-butan-2-one and butane-2,3-diol) are capable of displacing ANS, whereas two other pheromone components (E-2-octenoic acid and senecioic acid) and other alkyl volatile compounds are not capable of displacing ANS, indicating a certain filtering of binding, which can be correlated with the putative function.
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Kaskova, Margarita, and Olga Demina. "Texts rendering into a foreign language. Distant learning experience." E3S Web of Conferences 295 (2021): 05014. http://dx.doi.org/10.1051/e3sconf/202129505014.
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This article examines the effectiveness of pedagogical techniques and means of stimulating educational motivation during the classes “Rendering and annotating text in a foreign language” in distant learning in higher education. Experimental training was conducted to test the effectiveness of the authors’ electronic text rendering tutorial for students learning Italian as a second language. The experiment was carried out among the 2-nd and 3-rd year students of the Linguistics department in the Institute of Foreign Languages of the RUDN University in the 2019-2020 and 2020-2021 academic years. Currently e-learning has successfully integrated into the system of traditional education and is no longer seen as an alternative. The authors of this article focused on a combination of resources and tools from the Microsoft Teams platform and elaborated tutorial on rendering to motivate learners with distant learning. The article describes pedagogical practices for enhancing the motivation of students. We are talking about texts for rendering all major genres, functional styles, various topics, taking into account the level of students’ preparedness. With the aim of involving students in rendering activities and active expression of their own opinion, the researchers used an “ interpretive abstract “and included the paragraph “ OPPINIONE “ as its component. Experimental verification, its results and conclusions showed that combined rendering training based on e- tutorial developed by the authors and Microsoft Teams platform activates students’ motivation and contributes to their involvement in the process. The experiment showed another strong point of distant learning: it made a great contribution to the development of students’ independence, self-discipline and responsibility. 220.
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Mangaiyarkarasi, S. P., and T. Sree Renga Raja. "PSO Based Optimal Location and Sizing of SVC for Novel Multiobjective Voltage Stability Analysis during N – 2 Line Contingency." Archives of Electrical Engineering 63, no. 4 (2014): 535–50. http://dx.doi.org/10.2478/aee-2014-0037.
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Abstract In this paper voltage stability is analysed based not only on the voltage deviations from the nominal values but also on the number of limit violating buses and severity of voltage limit violations. The expression of the actual state of the system as a numerical index like severity, aids the system operator in taking better security related decisions at control centres both during a period of contingency and also at a highly stressed operating condition. In contrary to conventional N – 1 contingency analysis, Northern Electric Reliability Council (NERC) recommends N – 2 line contingency analysis. The decision of the system operator to overcome the present contingency state of the system must blend harmoniously with the stability of the system. Hence the work presents a novel N – 2 contingency analysis based on the continuous severity function of the system. The study is performed on 4005 possible combinations of N – 2 contingency states for the practical Indian Utility 62 bus system. Static VAr Compensator is used to improve voltage profile during line contingencies. A multi- objective optimization with the objective of minimizing the voltage deviation and also the number of limit violating bus with optimal location and optimal sizing of SVC is achieved by Particle Swarm Optimization algorithm.
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Wolfe, Amy, Kenneth David, and John Sherry. "It Depends on Where You Sit: Anthropologists' Involvement with Nanotechnology in Government, University, and Industry Settings." Practicing Anthropology 28, no. 2 (2006): 19–22. http://dx.doi.org/10.17730/praa.28.2.bw9r2518415u5740.
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This paper emerged from discussions during and after the spring 2005 SfAA session on anthropology and nanotechnology. The three authors have worked for many years in substantially different institutional settings. Wolfe has worked at Oak Ridge National Laboratory (ORNL), owned by the U.S. Department of Energy and currently managed by UT-Battelle, LLC, for a generation. David has resided at Michigan State University's anthropology department for even longer. Sherry is the relative newcomer, having worked at Intel for 9 years (after 2 years at Microsoft). When talking about the nanotechnology-related work we are, are endeavoring to, or are interested in pursuing, it became clear that our institutionally grounded perspectives varied substantially. Moreover, despite some commonalities, the ways in which we do or would engage in nanotechnology research also diverge. This article is a formalized expression of those commonalities and differences, and is indicative of the range of ways in which anthropologists may participate in research surrounding this potentially revolutionary set of technologies.
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Kalaoglu-Altan, Ozlem Ipek, Havva Baskan, Timo Meireman, et al. "Silver Nanoparticle-Coated Polyhydroxyalkanoate Based Electrospun Fibers for Wound Dressing Applications." Materials 14, no. 17 (2021): 4907. http://dx.doi.org/10.3390/ma14174907.
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Wound dressings are high performance and high value products which can improve the regeneration of damaged skin. In these products, bioresorption and biocompatibility play a key role. The aim of this study is to provide progress in this area via nanofabrication and antimicrobial natural materials. Polyhydroxyalkanoates (PHAs) are a bio-based family of polymers that possess high biocompatibility and skin regenerative properties. In this study, a blend of poly(3-hydroxybutyrate) (P(3HB)) and poly(3-hydroxyoctanoate-co-3-hydroxy decanoate) (P(3HO-co-3HD)) was electrospun into P(3HB))/P(3HO-co-3HD) nanofibers to obtain materials with a high surface area and good handling performance. The nanofibers were then modified with silver nanoparticles (AgNPs) via the dip-coating method. The silver-containing nanofiber meshes showed good cytocompatibility and interesting immunomodulatory properties in vitro, together with the capability of stimulating the human beta defensin 2 and cytokeratin expression in human keratinocytes (HaCaT cells), which makes them promising materials for wound dressing applications.
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Krumholz, Philipp, Armin Janß, and Klaus Radermacher. "Usability Evaluation of a One-Handed Touchbased OR-Table Control." Current Directions in Biomedical Engineering 4, no. 1 (2018): 157–60. http://dx.doi.org/10.1515/cdbme-2018-0039.
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AbstractDue to the increasing number and the complexity of devices in the operation room (OR), which are caused by the diversity and variety of proprietary interface designs, the probability for use errors increases. In order to ensure a safe intraoperative workflow in the OR, integrated OR systems with central work stations have been developed. For this, there also exist concepts for handhelds, which offer touchbased graphical user interfaces (GUI). However, those come along with various limitations, e.g. possibility for one-handed interaction, which is influenced i.a. by the size, the design and the working task. Within our investigations, requirements for an enhanced concept have been gathered by taking into account corresponding standards regarding ergonomics, riskmanagement and usability-engineering. According to DIN EN 60601-2-46, machinery directive 2006/42 EG and guideline VDI/VDE 3850, the stipulated user interface has been designed in order to preselect functions on the touchscreen and their subsequent activation by physical buttons. Furthermore, the accessibility of areas of interest has been considered on the touchscreen, to avoid the re-gripping of the handheld. As a first step, the OR-table control for a tablet has been realized with Microsoft Blend, using a 22’ touch monitor. The usability study has been conducted in accordance with DIN EN ISO 9241-11 and IEC 62366. A group of ten surgeons and OR nurses underwent multiple tasks in the framework of a usability test, comparing the developed concept with a common keypad handheld. The study showed comparable results concerning the usability criteria effectiveness and efficiency. However, the concept clearly outperforms the handheld regarding user satisfaction, in particular due to the higher learnability and the easy transfer of daily-used GUI skills. The current approach motivates to develop a functional model of a touch-based handheld for OR-tables as well as with further integrated OR devices and to conduct additional usability studies.
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Lis-Bartos, Anna, Agnieszka Smieszek, Kinga Frańczyk, and Krzysztof Marycz. "Fabrication, Characterization, and Cytotoxicity of Thermoplastic Polyurethane/Poly(lactic acid) Material Using Human Adipose Derived Mesenchymal Stromal Stem Cells (hASCs)." Polymers 10, no. 10 (2018): 1073. http://dx.doi.org/10.3390/polym10101073.
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Thermoplastic polyurethane (TPU) and poly(lactic acid) are types of biocompatible and degradable synthetic polymers required for biomedical applications. Physically blended (TPU+PLA) tissue engineering matrices were produced via solvent casting technique. The following types of polymer blend were prepared: (TPU+PLA) 7:3, (TPU+PLA) 6:4, (TPU+PLA) 4:6, and (TPU+PLA) 3:7. Various methods were employed to characterize the properties of these polymers: surface properties such as morphology (scanning electron microscopy), wettability (goniometry), and roughness (profilometric analysis). Analyses of hydrophilic and hydrophobic properties, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) of the obtained polymer blends were conducted. Tensile tests demonstrated that the blends exhibited a wide range of mechanical properties. Cytotoxicity of polymers was tested using human multipotent stromal cells derived from adipose tissue (hASC). In vitro assays revealed that (TPU+PLA) 3:7 matrices were the most cytocompatible biomaterials. Cells cultured on (TPU+PLA) 3:7 had proper morphology, growth pattern, and were distinguished by increased proliferative and metabolic activity. Additionally, it appeared that (TPU+PLA) 3:7 biomaterials showed antiapoptotic properties. hASC cultured on these matrices had reduced expression of Bax-α and increased expression of Bcl-2. This study demonstrated the feasibility of producing a biocompatible scaffold form based on (TPU+PLA) blends that have potential to be applied in tissue engineering.
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Pulido-Rodriguez, Lina Fernanda, Gloriana Cardinaletti, Giulia Secci, et al. "Appetite Regulation, Growth Performances and Fish Quality Are Modulated by Alternative Dietary Protein Ingredients in Gilthead Sea Bream (Sparus aurata) Culture." Animals 11, no. 7 (2021): 1919. http://dx.doi.org/10.3390/ani11071919.
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By answering the need for increasing sustainability in aquaculture, the present study aimed to compare growth, gene expression involved in appetite regulation, physical characteristics, and chemical composition of Sparus aurata fed alternative protein sources. Fish were fed ten iso-proteic, iso-lipidic, and isoenergetic diets: a vegetable-based (CV) and a marine ingredient-rich (CF) diet were set as control diets. The others were prepared by replacing graded levels (10, 20 or 40%) of the vegetable proteins in the CV with proteins from a commercial defatted Hermetia illucens pupae meal (H), poultry by-product meal (PBM) singly (H10, H20, H40, P20, P40) or in combination (H10P30), red swamp crayfish meal (RC10) and from a blend (2:1, w:w) of Tisochrysis lutea and Tetraselmis suecica (MA10) dried biomasses. The increase in ghre gene expression observed in MA10 fed fish matched with increased feed intake and increased feed conversion ratio. Besides, the MA10 diet conferred a lighter aspect to the fish skin (p < 0.05) than the others. Overall, no detrimental effects of H, PBM, and RC meal included in the diets were observed, and fish fatty acid profile resulted as comparable among these groups and CV, thus demonstrating the possibility to introduce H, PBM, and RC in partial replacement of vegetable proteins in the diet for Sparus aurata.
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Houston, Sam J. S., Vasileios Karalazos, John Tinsley, et al. "The compositional and metabolic responses of gilthead seabream (Sparus aurata) to a gradient of dietary fish oil and associatedn-3 long-chain PUFA content." British Journal of Nutrition 118, no. 12 (2017): 1010–22. http://dx.doi.org/10.1017/s0007114517002975.
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AbstractThe replacement of fish oil (FO) with vegetable oil (VO) in feed formulations reduces the availability ofn-3 long-chain PUFA (LC-PUFA) to marine fish such as gilthead seabream. The aim of this study was to examine compositional and physiological responses to a dietary gradient ofn-3 LC-PUFA. Six iso-energetic and iso-nitrogenous diets (D1–D6) were fed to seabream, with the added oil being a blend of FO and VO to achieve a dietary gradient ofn-3 LC-PUFA. Fish were sampled after 4 months feeding, to determine biochemical composition, tissue fatty acid concentrations and lipid metabolic gene expression. The results indicated a disturbance to lipid metabolism, with fat in the liver increased and fat deposits in the viscera reduced. Tissue fatty acid profiles were altered towards the fatty acid compositions of the diets. There was evidence of endogenous modification of dietary PUFA in the liver which correlated with the expression of fatty acid desaturase 2 (fads2). Expression of sterol regulatory element binding protein 1 (srebp1), fads2and fatty acid synthase increased in the liver, whereas PPARα1 pathways appeared to be supressed by dietary VO in a concentration-dependent manner. The effects in lipogenic genes appear to become measurable in D1–D3, which agrees with the weight gain data suggesting that disturbances to energy metabolism and lipogenesis may be related to performance differences. These findings suggested that suppression ofβ-oxidation and stimulation ofsrebp1-mediated lipogenesis may play a role in contributing toward steatosis in fish fedn-3 LC-PUFA deficient diets.
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Ogunade, Ibukun M., Devan M. Compart, and Andres A. Pech-Cervantes. "PSIX-22 Performance, whole-blood immune gene expression, and plasma metabolome of beef steers fed diet supplemented with a Saccharomyces cerevisiae-based direct-fed microbial product." Journal of Animal Science 98, Supplement_4 (2020): 420–21. http://dx.doi.org/10.1093/jas/skaa278.732.
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Abstract We examined the effects of dietary supplementation of a Saccharomyces cerevisiae-based direct-fed microbial on the performance, whole-blood immune gene expression, and plasma metabolome of beef steers during a 42-d receiving period. Forty newly weaned Angus crossbred steers (7 d post-weaning; 210 ± 12 kg of BW) were stratified by BW and randomly assigned to 1 of 2 treatments: basal diet with no additive (CON; n = 20) or a basal diet top-dressed with 19 g of the DFM (PROB; n = 20). PROB (PMI, Arden Hills, MN) is an optimized blend of 6.2 × 1011 cfu/g of S. cerevisiae, 3.5 × 1010 cfu/g of a mixture of Enterococcus lactis, Bacillus subtilis, Enterococcus faecium, and L. casei. Daily DMI and weekly body weights were measured to calculate average daily gain (ADG) and feed efficiency (FE). Expression of 84 immune-related genes was analyzed on whole blood samples collected on days 21 and 42. Plasma metabolome was analyzed on day 42. The data were analyzed using the GLIMMIX procedure of SAS with treatment as a fixed effect and BW as a random effect. Compared with CON, PROB increased or tended to increase final body weight (P = 0.01), ADG (P = 0.04), and FE (P = 0.10). Compared with CON, PROB increased (P ≤ 0.05) the expression of seven immune-related genes involved in detecting pathogen-associated molecular patterns and T-cell differentiation. Plasma metabolome analysis revealed an increase (P ≤ 0.05) in concentrations of ten metabolites involved in protecting the animals against inflammation in steers fed PROB diet. This study demonstrated that supplementation of PROB improved the performance and health of newly weaned beef steers during a 42-d receiving period.
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Yao, Mu, Chanlu Xie, Maryrose Constantine, et al. "How can food extracts consumed in the Mediterranean and East Asia suppress prostate cancer proliferation?" British Journal of Nutrition 108, no. 3 (2011): 424–30. http://dx.doi.org/10.1017/s0007114511005770.
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We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA-PCa-2b) with BBP (up to 0·8 %) for 72 h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2′-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation.
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Caixeta, E. S., P. Ripamonte, M. F. Machado, et al. "229 EXPRESSION OF mRNA ENCODING GLYCOLYTIC ENZYMES IN BOVINE CUMULUS CELLS DURING IN VITRO MATURATION: EFFECTS OF TIME AND FSH." Reproduction, Fertility and Development 22, no. 1 (2010): 272. http://dx.doi.org/10.1071/rdv22n1ab229.
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Mammalian oocytes require pyruvate as an energy source for growth and resumption of meiosis. Because oocytes are not competent to carry out glycolysis, cumulus cells (CC) are responsible for metabolizing glucose into pyruvate and providing it to the oocyte through gap junctions. The understanding of the energetic metabolism of CC in culture conditions might provide basis for the improvement of COC in vitro maturation. The aim of this study was to determine the temporal patterns of mRNA expression of glycolytic enzymes [phosphofructokinase (PFKP), aldolase (ALDOA), triosephosphate isomerase (TPI), enolase (ENO1), pyruvate kinase (PKM2), and lactate dehydrogenase (LDHA)] in bovine CC during COC in vitro maturation with or without FSH. Immature COC (grades 1 and 2) were obtained from 2- to 8-mm follicles from abattoir ovaries (predominantly Bos indicus). Cumulus cells were separated from COC and frozen before (immature group) or after COC culture for 4, 8, 12, 16, and 20 hours with (10 ng/mL) or without FSH. Total RNA was extracted using RNeasy® (Qiagen, Valencia, CA, USA), and 100 ng of RNA was reverse transcribed using oligo dT primers and Omniscript® (Qiagen). Relative expression of target genes was assessed by real-time PCR using bovine-specific primers and Power SYBR green master mix in an ABI Prism® 7300. To select the most stable housekeeping gene for expression normalization, cyclophilin-A (CYC-A), GAPDH, and histone H2AFZ amplification profiles were compared using the geNorm applet for Microsoft Excel (Vandesompele J et al. 2002 Genome Biol. 3, 1-11); the most stable housekeeping gene was CYC-A. Relative expression values were calculated using the AACt method with efficiency correction (Pfaffl MW 2001 Nucleic Acids Res. 29, 2002-2007). Effects of time in culture and of FSH treatment were tested by ANOVA, and groups were compared by Tukey-Kramer Honestly Significant Difference test. Nonparametric analysis was used when data were not normally distributed. Abundance of mRNA of all glycolytic enzymes decreased during in vitro maturation with or without FSH. Expression of PFKP, ALDOA, TPI1, ENO1, and LDHA genes was decreased to around half of the initial value (time 0) by 4 to 8 h of culture (P < 0.05) and did not increase thereafter. A similar expression pattern was observed for PKM2, although mRNA abundance was reduced later in comparison with other enzymes; levels were decreased by 16 (without FSH) to 20 h (with FSH) of culture. The presence of FSH did not alter the overall temporal pattern of gene expression but decreased mRNA abundance for PFKP, ALDOA, and TPI1 at 20, 16 and 16 h of culture, respectively. In conclusion, gene expression of glycolytic enzymes decreased with time during COC in vitro maturation in cattle, and FSH did not have a major influence on this expression pattern. This study was supported by CAPES and FAPESP.
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Majumdar, Abhishek, Yueze Liu, Yaoqin Lu, Shaofeng Wu, and Lijun Cheng. "kESVR: An Ensemble Model for Drug Response Prediction in Precision Medicine Using Cancer Cell Lines Gene Expression." Genes 12, no. 6 (2021): 844. http://dx.doi.org/10.3390/genes12060844.
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Background: Cancer cell lines are frequently used in research as in-vitro tumor models. Genomic data and large-scale drug screening have accelerated the right drug selection for cancer patients. Accuracy in drug response prediction is crucial for success. Due to data-type diversity and big data volume, few methods can integrative and efficiently find the principal low-dimensional manifold of the high-dimensional cancer multi-omics data to predict drug response in precision medicine. Method: A novelty k-means Ensemble Support Vector Regression (kESVR) is developed to predict each drug response values for single patient based on cell-line gene expression data. The kESVR is a blend of supervised and unsupervised learning methods and is entirely data driven. It utilizes embedded clustering (Principal Component Analysis and k-means clustering) and local regression (Support Vector Regression) to predict drug response and obtain the global pattern while overcoming missing data and outliers’ noise. Results: We compared the efficiency and accuracy of kESVR to 4 standard machine learning regression models: (1) simple linear regression, (2) support vector regression (3) random forest (quantile regression forest) and (4) back propagation neural network. Our results, which based on drug response across 610 cancer cells from Cancer Cell Line Encyclopedia (CCLE) and Cancer Therapeutics Response Portal (CTRP v2), proved to have the highest accuracy (smallest mean squared error (MSE) measure). We next compared kESVR with existing 17 drug response prediction models based a varied range of methods such as regression, Bayesian inference, matrix factorization and deep learning. After ranking the 18 models based on their accuracy of prediction, kESVR ranks first (best performing) in majority (74%) of the time. As for the remaining (26%) cases, kESVR still ranked in the top five performing models. Conclusion: In this paper we introduce a novel model (kESVR) for drug response prediction using high dimensional cell-line gene expression data. This model outperforms current existing prediction models in terms of prediction accuracy and speed and overcomes overfitting. This can be used in future to develop a robust drug response prediction system for cancer patients using the cancer cell-lines guidance and multi-omics data.
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Osmond, Angelisa T. Y., Michael T. Arts, Jennifer R. Hall, et al. "Schizochytrium sp. (T18) Oil as a Fish Oil Replacement in Diets for Juvenile Rainbow Trout (Oncorhynchus mykiss): Effects on Growth Performance, Tissue Fatty Acid Content, and Lipid-Related Transcript Expression." Animals 11, no. 4 (2021): 1185. http://dx.doi.org/10.3390/ani11041185.
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In this study, we evaluated whether oil extracted from the marine microbe, Schizochytrium sp. (strain T18), with high levels of docosahexaenoic acid (DHA), could replace fish oil (FO) in diets for rainbow trout (Oncorhynchus mykiss). Three experimental diets were tested: (1) a control diet with fish oil (FO diet), (2) a microbial oil (MO) diet with a blend of camelina oil (CO) referred to as MO/CO diet, and (3) a MO diet (at a higher inclusion level). Rainbow trout (18.8 ± 2.9 g fish−1 initial weight ± SD) were fed for 8 weeks and evaluated for growth performance, fatty acid content and transcript expression of lipid-related genes in liver and muscle. There were no differences in growth performance measurements among treatments. In liver and muscle, eicosapentaenoic acid (EPA) was highest in trout fed the FO diet compared to the MO/CO and MO diets. Liver DHA was highest in trout fed the MO/CO diet compared to the FO and MO diets. Muscle DHA was highest in trout fed the MO and MO/CO diets compared to the FO diet. In trout fed the MO/CO diet, compared to the MO diet, fadsd6b was higher in both liver and muscle. In trout fed the FO or MO/CO diets, compared to the MO diet, cox1a was higher in both liver and muscle, cpt1b1a was higher in liver and cpt1a1a, cpt1a1b and cpt1a2a were higher in muscle. Schizochytrium sp. (T18) oil was an effective source of DHA for rainbow trout.
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Morais, Sofia, Jarunan Pratoomyot, Bente E. Torstensen, et al. "Diet × genotype interactions in hepatic cholesterol and lipoprotein metabolism in Atlantic salmon (Salmo salar) in response to replacement of dietary fish oil with vegetable oil." British Journal of Nutrition 106, no. 10 (2011): 1457–69. http://dx.doi.org/10.1017/s0007114511001954.
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The present study investigates the effects of genotype on responses to alternative feeds in Atlantic salmon. Microarray analysis of the liver transcriptome of two family groups, lean or fat, fed a diet containing either a fish oil (FO) or a vegetable oil (VO) blend indicated that pathways of cholesterol and lipoprotein metabolism might be differentially affected by the diet depending on the genetic background of the fish, and this was further investigated by real-time quantitative PCR, plasma and lipoprotein biochemical analysis. Results indicate a reduction in VLDL and LDL levels, with no changes in HDL, when FO is replaced by VO in the lean family group, whereas in fat fish fed FO, levels of apoB-containing lipoproteins were low and comparable with those fed VO in both family groups. Significantly lower levels of plasma TAG and LDL-TAG were measured in the fat group that was independent of diet, whereas plasma cholesterol was significantly higher in fish fed the FO diet in both groups. Hepatic expression of genes involved in cholesterol homeostasis, β-oxidation and lipoprotein metabolism showed relatively subtle changes. A significantly lower expression of genes considered anti-atherogenic in mammals (ATP-binding cassette transporter A1, apoAI, scavenger receptor class B type 1, lipoprotein lipase (LPL)b (TC67836) and LPLc (TC84899)) was found in lean fish, compared with fat fish, when fed VO. Furthermore, the lean family group appeared to show a greater response to diet composition in the cholesterol biosynthesis pathway, mediated by sterol-responsive element-binding protein 2. Finally, the presence of three different transcripts for LPL, with differential patterns of nutritional regulation, was demonstrated.
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Matthews, J. C., and P. J. Bridges. "NutriPhysioGenomics applications to identify adaptations of cattle to consumption of ergot alkaloids and inorganic versus organic forms of selenium: altered nutritional, physiological and health states?" Animal Production Science 54, no. 10 (2014): 1594. http://dx.doi.org/10.1071/an14274.
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NutriPhysioGenomics (NPG) seeks to measure nutrition-responsive genome expression during specific physiological states, thus defining how a given challenge alters the ‘basal’ transcriptome. Application of NGS regimens (transcriptome and bioinformatics analyses) in combination with targeted-gene approaches has revealed cellular mechanisms putatively responsible for complex, whole-animal, metabolic syndromes such as heat stress and subacute ruminal acidosis. Using similar approaches, our laboratory sought to understand how the basal physiology of developing cattle adapted to two prevalent health challenges of forage-based beef cattle production in south-eastern USA: fescue toxicosis and selenium (Se) deficiency. In Model 1, pituitary and hepatic genomic expression profiles of growing beef steers grazing high (E+, n = 9) versus low (E–, n = 10) endophyte-infected tall fescue pastures for 85 days, and consuming sodium selenite (ISe) as a free-choice Se supplement, were compared by a combination of microarray, bioinformatic, and targeted-gene/protein (real-time reverse transcription–PCR, Nanostring, immunoblot) analyses. In Model 2, hepatic genomic expression profiles of growing beef heifers (0.5 kg gain/day) fed a cotton seed hull-based diet and different sources (n = 9) of dietary Se (3 mg/day) supplements (no supplement, Control; inorganic Se, sodium selenite, ISe; organic Se, Sel-Plex; OSe), or a 1.5 mg : 1.5 mg blend of ISe and OSe, MIX) were compared after 168 days of supplementation, as described for Model 1. The results for Model 1 showed, that in the pituitary of E+ steers, expression of genes for prolactin signalling; redox capacity; regulation of lactotroph, gonadotroph, and thyrotroph proliferation; gonadotropin-releasing hormone-mediated signalling; and Se-based metabolism was impaired. Concomitantly, the livers of E+ steers had an increased level of expression of genes encoding proteins responsible for shunting of amino acid carbons into pyruvate and ATP synthesis capacity (oxidative phosphorylation pathway, mitochondrial mass), increased serine and proline biosynthesis, and reduced selenoprotein-mediated metabolism. Result for Model 2 showed that, overall, there were clear differences in the profiles of differentially expressed genes (DEG) among the four Se treatment groups, with the form of Se administered being more reflective of DEG profiles than the total amount of Se assimilated. Moreover, hepatic transcriptomes profiles of MIX heifers revealed an increased potential for selenoprotein synthesis and selenoprotein-mediated metabolism. In addition, several genes involved with increased redox capacity were upregulated in MIX versus ISe heifers. Taken together, our NGS approach characterised adaptation to physiological challenges and, serendipitously, identified suppression of several metabolic pathways by consumption of ergot alkaloid consumption that have the potential to be increased with supplementation of the MIX form of Se.
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Un Nisa, Kaiser, and Mohammad Irshad Reza. "Key Relevance of Epigenetic Programming of Adiponectin Gene in Pathogenesis of Metabolic Disorders." Endocrine, Metabolic & Immune Disorders - Drug Targets 20, no. 4 (2020): 506–17. http://dx.doi.org/10.2174/1871530319666190801142637.
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Background & Objective:: Significant health and social burdens have been created by the growth of metabolic disorders like type 2 diabetes mellitus (T2DM), atherosclerosis, and non-alcoholic steatohepatitis, worldwide. The number of the affected population is as yet rising, and it is assessed that until 2030, 4−5 million individuals will acquire diabetes. A blend of environmental, genetic, epigenetic, and other factors, such as diet, are accountable for the initiation and progression of metabolic disorders. Several researches have shown strong relevance of adiponectin gene and metabolic disorders. In this review, the potential influence of epigenetic mechanisms of adiponectin gene “ADIPOQ” on increasing the risk of developing metabolic disorders and their potential in treating this major disorder are discussed. Results & Conclusion:: Various studies have postulated that a series of factors such as maternal High fat diet (HFD), oxidative stress, pro-inflammatory mediators, sleep fragmentation throughout lifetime, from gestation to old age, could accumulate epigenetic marks, including histone remodeling, DNA methylation, and microRNAs (miRNAs) that, in turn, alter the expression of ADIPOQ gene and result in hypoadiponectinemia which precipitates insulin resistance (IR) that in turn might induce or accelerate the onset and development of metabolic disorder. A better understanding of global patterns of epigenetic modifications and further their alterations in metabolic disorders will bestow better treatment strategies design.
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Shen, C., L. G. Christensen, S. Y. Bak, N. Christensen, and K. Kragh. "Immunomodulatory effects of thymol and cinnamaldehyde in chicken cell lines." Journal of Applied Animal Nutrition 8, no. 1 (2020): 21–30. http://dx.doi.org/10.3920/jaan2020.0001.
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Thymol and cinnamaldehyde are phytogenic feed additives that have been developed to improve gut health, immunity and growth performance in poultry and swine. This study evaluated the immune modulating effects of a thymol and cinnamaldehyde blend (TCB) in the intestinal system of poultry in vitro, using two chicken cell lines, LMH (liver cell line) which has been used to mimic epithelial cell responses, and HD-11 (monocyte/macrophage-like). Cells with high viability (>95%) from established cell lines were cultured in the presence of TCB at concentrations ranging from 1 ng/ml to 100 ng/ml. The viability, transepithelial electrical resistance (TEER) and phagocytic capacity of co-cultured LMH cells, with or without stimulation with lipopolysaccharide (LPS), was subsequently evaluated. The expression of cytokines, chemokines and pattern recognition receptors by HD-11 monocytes/macrophages was measured by RT-PCR and by proteomic analysis. TCB was well tolerated by both cell lines (cell viability >90% after co-culture with TCB at 100 ng/ml for 48 h with or without LPS). Epithelial integrity of LMH cells (as assessed by TEER) was increased by TCB (10 ng/ml) after 4 h incubation, versus untreated controls, and phagocytic capacity of HD-11 cells was increased, in a dose-dependent manner (P<0.05). In HD-11 cells, TCB (10 ng/ml) downregulated the relative expression of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8 and the transcription factor cyclooxygenase-2 and upregulated expression of anti-inflammatory IL-10, versus untreated controls (P<0.05). In summary, under the tested conditions, TCB enhanced the epithelial barrier integrity of poultry hepatocytes, increased phagocytic activity and production of anti-inflammatory cytokines by monocytes and macrophages. These results indicated how supplementing TCB in poultry diets can increase bird performance, by increasing in vivo cell membrane integrity (especially important in the gut) and assisting in immune responses, which can liberate energy for growth.
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Shen, C., L. G. Christensen, P. B. Rasmussen, and K. M. Kragh. "In vitro immunomodulatory effects of thymol and cinnamaldehyde in a pig intestinal epithelial cell line (IPEC-J2)." Journal of Applied Animal Nutrition 8, no. 3 (2020): 127–34. http://dx.doi.org/10.3920/jaan2020.0010.
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Thymol and cinnamaldehyde are phytogenic feed additives developed to improve gut health and growth performance in poultry and swine. This study evaluated the in vitro immune modulating effects of thymol and cinnamaldehyde blend (TCB) in a porcine gut epithelial cell line (IPEC-J2), with or without cellular damage caused by challenge with lipopolysaccharides. Cytotoxicity, permeability, wound-healing and bacteria adhesion assays were recorded. The expression of cytokines, tight junctions and polymeric immunoglobulin receptor (pIgR) were measured by RT-PCR. The IPEC-J2 cells were cultured in the presence of TCB at concentrations ranging from 1 ng/ml to 1 μg/ml and displayed high viability (>90%). TCB increased barrier integrity (13.8% less in lipopolysaccharide challenge which induced gut epithelial leakage, P<0.05) and accelerated the initial speed of wound recovery (day 1, 26% wound recovery in TCB treated vs 7% in control, P<0.05; day 2, 54 vs 39%, P<0.001). The RT-PCR analysis of cell culture showed that TCB upregulated anti-inflammatory cytokine interleukin (IL)-10 (73.3%, P<0.05) in non-stimulated IPEC-J2 cells, while, when stimulated, pIgR (9.7%, P<0.05) and tight junctions claudin-4 (9.4%, P<0.05) were upregulated by TCB. Furthermore, TCB significantly increased Lactobacillus acidophilus adherence to gut epithelial cells (285.0%, P<0.05). Overall, the current in vitro study showed that TCB can induce various immune responses, which may explain its in vivo benefits as feed additive.
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Amadi, Beatrice, Kanekwa Zyambo, Kanta Chandwe, et al. "Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting." Nature Microbiology 6, no. 4 (2021): 445–54. http://dx.doi.org/10.1038/s41564-020-00849-w.
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AbstractEnvironmental enteropathy is a major contributor to growth faltering in millions of children in Africa and South Asia. We carried out a longitudinal, observational and interventional study in Lusaka, Zambia, of 297 children with stunting (aged 2–17 months at recruitment) and 46 control children who had good growth (aged 1–5 months at recruitment). Control children contributed data only at baseline. Children were provided with nutritional supplementation of daily cornmeal-soy blend, an egg and a micronutrient sprinkle, and were followed up to 24 months of age. Children whose growth did not improve over 4–6 months of nutritional supplementation were classified as having non-responsive stunting. We monitored microbial translocation from the gut lumen to the bloodstream in the cohort with non-responsive stunting (n = 108) by measuring circulating lipopolysaccharide (LPS), LPS-binding protein and soluble CD14 at baseline and when non-response was declared. We found that microbial translocation decreased with increasing age, such that LPS declined in 81 (75%) of 108 children with non-responsive stunting, despite sustained pathogen pressure and ongoing intestinal epithelial damage. We used confocal laser endomicroscopy and found that mucosal leakiness also declined with age. However, expression of brush border enzyme, nutrient transporter and mucosal barrier genes in intestinal biopsies did not change with age or correlate with biomarkers of microbial translocation. We propose that environmental enteropathy arises through adaptation to pathogen-mediated epithelial damage. Although environmental enteropathy reduces microbial translocation, it does so at the cost of impaired growth. The reduced epithelial surface area imposed by villus blunting may explain these findings.
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Chudilova, G. A., I. V. Nesterova, T. V. Rusinova, et al. "Systemic and local effective function of neutrophilic granulocytes associated with transformation of the phenotype of their functionally significant subset in children with small purulent infection." RUDN Journal of Medicine 24, no. 3 (2020): 218–26. http://dx.doi.org/10.22363/2313-0245-2020-24-3-218-226.
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Defects in the functioning of neutrophilic granulocytes (NG) are accompanied by various purulent-inflammatory diseases that have a persistent-relapsing course. The bactericidal activity of NG, the processes of intracellular and extracellular killing of bacteria, is directly dependent on their phenotypic features: the expression level of functionally significant membrane receptors CD64, CD16, CD32, CD11b triggering effector processes. It was shown that there are subsets of NG with different phenotypic characteristics and the course and outcome of infectious and inflammatory diseases directly depends on their usefulness. Despite the large amount of accumulated information, the question of the transformation of NG subpopulations phenotype during NG response formation in children with local purulent processes of soft tissues - a small purulent infection (SPI) remains poorly understood. Purpose: to evaluate the local and systemic effector function of neutrophilic granulocytes (phagocytosis, NET formation) with clarification of the phenotype of functionally significant CD64-CD16+CD32+CD11b+, CD64+CD16+CD32+CD11b+ and CD64-CD16+CD32-CD11b+ NG subpopulations in peripheral blood (PB) in children with SPI. Materials and methods. We evaluated the phagocytic function of NG in 60 PB samples of children 5-9 years old, on the 2-3rd day of acute purulent process, before surgery, in smears - prints taken from the local focus of purulent inflammation and 17 PB samples of conditionally healthy children. Also the ability to form NET was additionally determined in smears-prints in children with SPI. In parallel, in PB we evaluated:% NG simultaneously carrying CD64, CD16, CD32, CD11b receptors and their expression density (MFI) by flow cytometry (CYTOMICS FC500, Beckman Coulter, USA). Statistical data processing was performed in the Microsoft Exel 2016 and Stat Plus 2010 software packages. Nonparametric criteria were used: median (Me) and interquartile range (Q1; Q3), Mann-Whitney U-test and Wilcoxon test. Results . We found a significant increase in the content of the NG subpopulation with a negatively transformed phenotype CD64-CD16+CD32-CD11b+ with defects in the expression of CD64 and CD32 receptors, which is the cause of inadequate inclusion of NG in inflammatory processes, disruption of phagocytic activity at the systemic and local levels and the occurrence of SPI in children. The formation of NET in the first stage is necessary to supplement the effector function of NG in order to compensate for disorders of phagocytosis.
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Necchi, Andrea, Petros Grivas, Gennady Bratslavsky, et al. "Contrasting genomic profiles in post-systemic treatment metastatic sites (MET), pretreatment primary tumors (PT), and liquid biopsies (LB) of clinically advanced prostate cancer (PC)." Journal of Clinical Oncology 38, no. 15_suppl (2020): 5534. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.5534.
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5534 Background: Comprehensive genomic profiling (CGP) was done on pre-systemic treatment (pre) PT, post-treatment (post) MET sites and LB in PC to uncover differences in genomic alterations (GA) and potential impact on therapy selection. Methods: 1,294 PC tissues and 782 LB underwent hybrid-capture based CGP. PT biopsies and resections were compared with post-treatment MET biopsies from bone (BO), liver (LIV), lung (LU), brain (BN), lymph node (LN) and soft tissue (ST) sites and LB. TMB was determined on up to 1.1 Mbp of sequenced DNA for tumor samples. Tumor cell PD-L1 IHC was measured (Dako 22C3). Results: Differences in alteration frequencies between PT, MET and LB for selected genes are shown in the Table. TMPRSS2:ERG fusion frequencies were similar between PT and MET (35% vs 33%) but varied between MET sites (27% in BO and ST to 40% in LN). GA in AR were lowest in pre PT (2%) and highest in MET (24% in LU to 50% in LIV). BN had the highest GA/tumor (8) and the most PTEN GA. BRCA2 GA frequency varied from 0% in BN to 15% in LI. Potential predictors of IO response included CDK12 GA (16% in LU) and MSI high status (29% in BN). High PD-L1 expression was found in only two cases (LN) and low PD-L1 expression was relatively uncommon. ERBB2 amplifications were increased in MET compared with PT. RB1 GA were increased in LIV cases. LB GA had a similar increase in AR and TP53 GA to MET and appeared to be a blend of MET site biopsies across alteration frequencies. Conclusions: CGP of PT, MET and LB in PC demonstrates differences most likely associated with exposure to systemic therapies. Differences identified in the MET GA landscape suggest that liquid biopsies may capture a broader range of therapeutic opportunities for PC patients. [Table: see text]
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Berdyugina, О. V. "Is there a dependence between expression of integrin receptors by peripheral blood immune cells and duration of tuberculous granuloma existence in the patients?" Medical Immunology (Russia) 22, no. 5 (2020): 867–78. http://dx.doi.org/10.15789/1563-0625-ita-2088.
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Over recent years, the number of patients with tuberculosis has not decreased in the country and in worldwide. This is due to high resistance of the pathogen and changing mechanisms of bacterial perception by the human immune system thus requiring closer examination of the issue. Cell fusion during the formation of pulmonary tuberculous granuloma involves a large number of adhesive events. Importance of α1β1 integrin has been shown for the granuloma integrity during the chronic phase of infection. It has been proven that pulmonary tuberculous granuloma should be monitored, including with the detection of cells expressing CD11c, since they support the continuous priming of T cells at different stages of infection. The aim of this study was to answer the question, if there is a different expression of integrin receptors by immune cells from the patient’s peripheral blood at different stages of the existence of pulmonary tuberculous granuloma? The study involved 38 people: the first group (control) consisted of 15 practically healthy people; a second group included 11 subjects with pulmonary tuberculous granuloma; the condition was first diagnosed 2 to 10 months before the present study. A third group consisted of 12 patients with pulmonary tuberculous granuloma, with primary diagnosis established 12 to 219 months before this study. All the participants underwent a general clinical blood tests using a 5 Diff Mythic 22 AL analyzer (Cormay, Poland). The adhesion markers CD11b, CD11c were detected with a Coulter Epicx XL instrument (Beckman Coulter, USA). The following peripheral blood cell populations were determined: CD14- CD13lowCD11b+, CD14- CD13lowCD11c+, CD14+CD11b+, CD14+CD11c+, CD45+CD3- CD16+CD56+, CD45+CD3- CD16+CD56+CD11b+. Statistical processing of the results was performed in the Windows 10 operating environment (Microsoft Corp., USA), using Statistica v. 12.5 software (StatSoft, USA). Kruskal–Wallis one-way analysis of variance (pk-w), with differences significant at p < 0.017, as well as the Wald–Wolfowitz test (pw-w) at a significance level of p < 0.05 were used as criteria for assessing differences between the compared groups. In addition, cluster and factor analysis were implemented. When studying the role of β2-integrins, we have found that they play an important role in maintaining the existence of pulmonary tuberculous granuloma. An increase in total number of granulocytes, and CD11b-expressing granulocytes, a decrease in the population of lymphocytes, NK cells and NK cells expressing CD11c proved to be distinctive in cases of pulmonary tuberculous granuloma detected 0.5 years before the study. Characteristic changes observed in the study of peripheral blood in the patients with pulmonary tuberculous granuloma detected 9.5 years before the study were as follows: an increase in the leukocyte population, total monocyte number, as well as CD11band CD11c-expressing monocytes.
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Janovska, Jana, Aleksejs Zavorins, Julija Voicehovska, et al. "SKIN CHANGES AND PECULIARITIES IN PATIENTS WITH METABOLIC SYNDROME." CBU International Conference Proceedings 1 (June 30, 2013): 264–71. http://dx.doi.org/10.12955/cbup.v1.43.
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Approximately 20-25 % of the World’s adult population aged 40 - 75 years have metabolic syndrome (MS). MS is one of the most widespread risk factors for: diabetes mellitus, cardiovascular disorders and skin disorders MS, due to the oxidative stress, supports a chronic inflammatory reaction in the skin and in the other parts of the body. During oxidative stress the net amount of reactive oxygen species (ROS) exceeds the antioxidant capacity of the body causing lipid peroxidation, protein oxidation and oxidative DNA damage. The role of oxidative stress in pathogenesis of early skin changes in patients with MS is not clearly defined. The aim of our study was to compare visual skin changes between patients with MS and without it, and to reveal early histological manifestations of MS in the skin. The study was conducted at the Clinic of Aesthetic Dermatology, Riga, Latvia. 50 patients aged 45-55 were enrolled. The research consisted of a clinical examination, biochemical testing and Punch biopsies. Tissue samples were stained with haematoxylin-eosin, Masson’s Trichrome and also immunohistochemically stainining with antibodies to CD34, CD117, CD20, CD8 and bcl-2. CD1a positive Langerhans cells were evaluated in 3 fields of vision. Data was analyzed with Microsoft Excel 2010 software. Gender ratio was women: men= 1.6:1. Histological changes in the skin of patients with MS were: hyperkeratosis, acanthosis, dermal fibrosis, elastosis and mild thickening of the stratum spinosum. Infiltrates around blood vessels were composed of T lymphocytes (CD3+). More significant expression and accumulation of apoptotic protein Bcl2 in skin of patients with MS in comparison to patients without MS was noted. Initial skin histological changes in MS are dermal elastosis, thickening of stratum spinosum and acanthosis. Mild T lymphocytic infiltration around capillaries possibly reflects the inflammatory component of MS. Increased accumulation of bcl2 anti-apoptotic protein in epidermis was more significantly expressed in patients with MS.
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Shapira, I., R. Huffman, E. Neculiseanu, et al. "P2: SNP ANALYSIS IN BRCA POSITIVE AND BRCA NEGATIVE SUBJECTS WITH AND WITHOUT BREAST CANCER (BRCA) REVEAL CENTRAL ROLE OF ALK SNPS AND TGFBETA SUPERFAMILY IN MALIGNANT TRANSFORMATION." Journal of Investigative Medicine 64, no. 3 (2016): 817.3–818. http://dx.doi.org/10.1136/jim-2016-000080.42.
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Purpose of StudyOver 240,000 individuals are diagnosed with breast cancer each year in the USA. Outcomes depend on DNA deregulations in tumors. Carriers of deleterious BRCA1 and BRCA2 mutations are predisposed to 30 fold higher lifetime risks of breast and ovarian cancer.Aims:1. To check for differences in SNPs of genomic DNA obtained in BRCA+/− with and without BrCa.2. Analyze correlates of molecular mechanisms occurring in BRCA mutant patients.Methods UsedWe analyzed 94 subjects (41 BRCA positive) with or without BrCa to detect SNPs whose expression is significantly differentially expressed between breast cancer and controls. DNA samples were extracted from PBMCs. Samples were measured for DNA concentration using an Invitrogen QuBit Fluorometer, and diluted to 50 ng/µL.All samples were collected between 2010 and 2014 and survival data was known in all cancer patients. Processed samples were sequenced using an Illumina MiSeq Sequencer with a 300 cycle kit to detect SNPs. Variant Call Files were analyzed in Microsoft Excel using Fisher's Exact Test.Summary of ResultsALK SNPs were commonly found in cancer relative to control. Significant associations of ALK SNPs were seen in BRCA mutation subjects. ALK protein was overexpressed in 47% of BRCA mutations cases, which was significantly higher than in non-BRCA cases. Our results show that the ALK signaling pathway possibly is more common in early onset of breast cancer as seen with BRCA mutations. Coremine analysis showed SNPs identified in cancer were most commonly associated with deregulation of Transforming Growth Factor-Beta Superfamily protein synthesis and binding function.ConclusionsDifferences in the associations of the modifying polymorphisms with BrCarisk for BRCA1 and BRCA2 mutation carriers are likely to reflect differences in the biology of tumor development in these two groups of women at high risk of breast cancer. The identification of modifying polymorphisms could therefore lead to a better understanding of the etiology of tumors in mutation carriers and also to the development of effective and more specific therapies for BrCa in mutation carriers.
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Reinwald, Mark, Anjulie Haag, Eva Lengfelder, et al. "Genome Wide DNA Methylation Analysis Identifies a Characteristic Methylation Profile for Patients with Acute Promyelocytic Leukemia and FLT3-Internal Tandem Duplication." Blood 120, no. 21 (2012): 3521. http://dx.doi.org/10.1182/blood.v120.21.3521.3521.
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Abstract Abstract 3521 Background Acute promyelocytic leukemia (APL) accounts for approximately 5% of all acute myeloid leukemias (AML). The characteristic molecular feature of APL is a fusion product named PML-RARA which acts as transcriptional repressor that affects gene expression patterns involved in differentiation, apoptosis, and self-renewal. The internal tandem duplication of the Fms-related Tyrosine-like Kinase 3 (FLT3-ITD) confers a poor prognosis in non-APL AML, however its effect in APL is still under discussion as several investigators found no prognostic influence for FLT3-ITD in APL. Aberrant DNA-promotor-methylation of tumor suppressor genes contributes significantly to leukemogenesis and oncogenic transformation. Deneberg et al. recently identified characteristic methylation profiles for cytogenetically normal AML, however no specific methylation profile was associated with FLT3-ITD in a study that excluded APL. To further elucidate the influence of aberrant methylation in FLT3-positive APL we carried out a genome wide DNA methylation analysis on APL samples with and without FLT3-ITD. Methods In total, genomic DNA from blasts of 54 APL patients at initial diagnosis (bone marrow n=32, peripheral blood n=22) were analyzed (median age 46 years, gender: 35 female, 19 male, blast count median 80%). The molecular analysis was carried out with written informed consent, with permission of the institutional review board and in accordance with the declaration of Helsinki. DNA was extracted using the QIAGEN Allprep Kit® (Qiagen, Hilden, Germany). Genome wide DNA methylation analysis was performed using the HumanMethylation450 BeadChip (Illumina, San Diego, USA). Differential methylation of CpGs was defined by a minimum mean methylation difference of 25% as expressed by the beta-value of the array data and statistical significance set at q ≤ 0.01 according to the Benjamini-Hochberg-method for multiple significance testing. Analysis of array data was performed using Genome-Studio Software® (Illumina, San Diego, USA), Qlucore Omics explorer 2.3 (Qlucore software. Lund, Sweden) and Microsoft Excel 10.1® (Microsoft Software, Redmond, USA). Pyrosequencing was performed to validate methylation changes as detected by the array-based analysis. Results The methylation pattern of FLT3-ITD-positive APL (n=18) patients was analyzed and compared to patients without FLT3-ITD (n=32) or D835 Mutation (n=4). We identified 133 CpGs that were significantly differentially methylated in FLT3-ITD-positive APL as compared to FLT3-ITD-negative APL. The most significant differential methylation was observed for 5 CpGs showing a strong hypomethylation of the chemokine (C-C motif) receptor 6 (CCR6) in FLT3-ITD-APL as compared to FLT3-negative APL (q-value < 6.9 *10−13). Other interesting target genes showing pronounced hypomethylation in FLT3-ITD positive APL samples belonged to the family of phosphatases such as the dual specificity phosphatase 5 (DUSP5), protein tyrosine phosphatase, receptor type, N polypeptide 2 (PTPRN2) and protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1). The most prominent hypermethylation in FLT3-ITD APL was observed in CpGs within the coding region of suppressor of cytokine signaling 2 (SOCS2) and significantly discriminated between FLT3-ITD and FLT3-negative APL (q-value < 10−5). The results of the genome-wide analysis obtained with the Illumina 450K BeadChip were validated for 4 CPGs in 10 samples via pyrosequencing and showed a robust Pearson correlation of 0.92 suggesting a good and reliable performance of the Illumina 450 K Bead Chip Assay. Conclusions The current study represents a comprehensive genome wide methylation analysis of a clinically well-defined cohort of APL patients. We here demonstrate for the first time that in contrast to cytogenetically normal AML, APL patients with FLT3-ITDs display a highly specific and disease defining DNA methylation profile. Thereby key regulators of cellular growth signaling such as SOC2, PTPRN2 and DUSP5 are significantly differentially methylated in dependency of FLT3-ITD status. This suggests that a cooperative effect between PML-RARA and FLT3-ITD is mediated by dysregulation of DNA methylation. Disclosures: No relevant conflicts of interest to declare.
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Nedogoda, Sergey Vladimirovich, Alla Sergeevna Salasyuk, Irina Nikolaevna Barykina, Victoria Olegovna Smirnova, and Ekaterina Andreevna Popova. "Assessment of Clinical and Economic Effectiveness of Alectinib for Patients with ALK+ Non-Small Cell Lung Cancer without Previous Experience of Targeted Therapy." Medical Technologies. Assessment and Choice (Медицинские технологии. Оценка и выбор), no. 4 (38) (December 1, 2019): 87–100. http://dx.doi.org/10.31556/2219-0678.2019.38.4.087-100.
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Aim: to assess economic consequences of alectinib compared with the recommended therapy schemes for patients with non-small cell lung cancer (NSCLC) with tumor expression of anaplastic lymphoma kinase (ALK+) without previous experience of targeted therapy from the Russian healthcare system perspective. Material and methods. Markov model was developed in Microsoft Excel 2010 software for cost calculation. 5-year costs of alectinib, crizotinib and ceritinib were calculated, taking into account the differences in clinical effectiveness and safety of the compared drugs. Data about clinical effectiveness and safety were derived from the network meta-analysis Steenrod A. et al, 2018, where alectinib showed superior effectiveness in the first line of therapy for ALK+ NSCLC vs crizotinib and ceritinib: relative risk (RR) of progression-free survival (PFS) was 0,50 (95% confidence interval 0,36–0,70) and 0,41 (0,25–0,67) respectively. Safety of alectinib in the first line therapy was superior to the safety of ceritinib – RR of severe adverse events (SAE)3–4 grade 0,36 (95% CI 0,17–0,79), – and was comparable with safety of chemotherapy and crizotinib – RR of SAE 3–4 grade 0,81 (95% CI 0,44–1,52) and 0,65 (95% CI 0,51–1,04) respectively. Cost effectiveness analyses and budget impact analysis were conducted from the Russian healthcare system perspective. Results. Cost of one year course of alectinib was 3 431 970 rubles, which was comparable with crizotinib (3 435 405 rub.) and 55% higher than the one-year cost of ceritinib. Cost-effectiveness ratio was lower for alectinib compared with crizotinib, incremental cost-effectiveness ratio (ICER) for alectinib vs crizotinib was 2 735 900 rub., which was 66% lower than ICER for ceritinib vs crizotinib. Given the number of patients eligible for alectinib, it’s impact on State Guarantees Program of Free Medical Care is not much. Sensitivity analysis showed that the results of budget impact assessment are stable. Conclusion. Alectinib is a preferred option for patients with ALK+ NSCLC from economic point of view. It doesn’t have a significant impact on the budget within the State Guarantees Program of Free Medical Care, and also has higher effectiveness compared with crizotinib and ceritinib and better safety when compared with ceritinib.
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Scheucher, Priscila S., Guilherme A. dos Santos, Hamilton L. Gimenes Teixeira, et al. "Caffeic Acid Phenetyl Ester, a Brazilian-Green-Propolis Derivative, Induces apoptosis in AML Cells, Promotes up Regulation of G-Protein Signaling and Hyper Secretion of IL-8." Blood 116, no. 21 (2010): 3274. http://dx.doi.org/10.1182/blood.v116.21.3274.3274.
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Abstract Abstract 3274 Propolis is a generic name for an adhesive resin collected, processed and used by bees to plug gaps, smooth internal walls and protect the entrance of the hive from intruders. Chemically is a complex blend of resin and fragments of plant tissues, volatile substances and wax. It contains over 300 constituents including benzoic acids, flavonoids and cinnamic acid derivatives. The Brazilian green propolis (BGP) has been shown to have immunomodulatory and antitumor properties in vitro and in vivo. We selected the caffeic acid phenethyl ester (CAPE), which is one of the components of BGP, as a candidate molecule for further studies regarding the antineoplastic activity. Cytotoxicity induced by Brazilian green propolis alcoholic extract (BGPAE) and CAPE in the cell lineages of acute promyelocytic leukemia (APL) (NB4 and NB4R2), and bone marrow cells from patients with acute myeloid leukemia (AML) at diagnosis (primary cells) was evaluated by annexin V/propidium iodide staining and analyzed by flow cytometry. BGPAE and CAPE showed antiproliferative and apoptotic activity and this effect was dose and time dependent (Table 1 and 2). Accordingly, in primary cells, CAPE (32μg/ml) for 24 hours significantly increased the percentage of apoptotic cells compared to control. The median (25 and 75 percentiles) for the percentage of apoptotic cells was 17.32% (13-27%) in control and 37% (24-52%) in CAPE, p-value = 0.0008 The cell cycle was analysed by flow cytometry using propidium iodide staining and demonstrated that CAPE blocked the cell cycle at G2/M. In addition, CAPE induced activation of caspases 3 and 9, as determined by Western blot, thus suggesting the involvement of the intrinsic pathway of apoptosis. The modulation of gene expression induced by CAPE in NB4 was determined by microarray using the CodeLink Uniset Human I bioarray (Amersham/GE) and analyzing 10,000 genes. Adopting a False Discovery Rate of 4.72% and using the Significance Analysis of Miroarray (SAM) software, we detected an increased expression of: negative mediators of cell cycle, including the dual specific phosphatases CDC14A, CDC14B and the cyclin-dependent kinase (CDK) inhibitor CDKN1A (p21/CIP1); protein phosphatases; chemokines and molecules associated with signaling by G protein. Furthermore, CAPE induced a decrease in gene expression of: positive mediators of cell cycle (including CDK4 and CCNA2); genes related to the “spliceosome” and protein translation. The most important differences in gene expression were confirmed by real time PCR using Taqman® technology (Applied Biosystems). Based on the microarray analysis, we decided to further study the production of IL-8 induced by CAPE in NB4 cells. Using an ELISA assay, it was detected a time dependent increase in the production of IL-8 at CAPE concentrations of 16 and 32μg/ml that was significantly higher than in controls at 12 and 24h of treatment. In conclusion, our results demonstrate that CAPE was able to block the cell cycle and induce apoptosis in APL cells, and induce the production of IL-8 ALP cells. Table 1 Effective doses 50% (ED-50) of BGPAE ( g/ml) for inhibition of proliferation and induction of apoptosis in NB4 and NB4R2 cell lines in 24, 48 and 72 hours of treatment time ED-50 CI 95% for DE-50 Proliferation NB4 24h 63,72 51,39 + 79,00 48h 43,00 37,20 – 49,70 72h 33,51 30,93 – 36,30 NB4R2 24h 30,28 25,42 – 36,06 48h 50,61 46,52 – 55,06 72h 50,40 45,15 – 56,27 Apoptosis NB4 24h 214,2 204,2 – 224,6 48h 201,0 189,0 – 213,8 72h 185,4 172,2 – 199,5 NB4R2 24h 139,0 132,7 – 145,5 48h 117,3 112,3 – 122,5 72h 101,5 95,18 – 108,2 Table 2 Effective doses 50% (ED-50) of CAPE (μg/ml) for inhibition of proliferation and induction of apoptosis in NB4 and NB4R2 cell lines in 24, 48 and 72 hours of treatment time ED-50 CI 95% for DE-50 Proliferation NB4 24h 8,106 6,977 – 9,418 48h 2,945 2,571 – 3,373 72h 1,648 1,451 – 1,872 NB4R2 24h 7,029 6,209 – 7,956 48h 4,342 4,017 – 4,694 72h 3,214 3,052 – 3,384 Apoptosis NB4 24h 51,81 44,67 – 60,10 48h 31,88 28,71 – 35,39 72h 21,38 18,99 – 24,07 NB4R2 24h 68,58 58,66 – 80,18 48h 34,92 30,39 – 40,14 72h 27,02 24,26 – 30,09 Disclosures: No relevant conflicts of interest to declare.
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Loges, Sonja, Michael Heuser, Joerg Chromik, et al. "Final Analysis of the Dose Escalation, Expansion and Biomarker Correlations in the Ph I/II Trial BGBC003 with the Selective Oral AXL Inhibitor Bemcentinib (BGB324) in Relapsed/Refractory AML and MDS." Blood 132, Supplement 1 (2018): 2672. http://dx.doi.org/10.1182/blood-2018-99-120380.
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Abstract Background AXL has been established as an independent prognostic factor in AML. AXL also represents a novel immune checkpoint because it directly inhibits NK cells and suppresses antigen presentation by antigen-presenting cells. Bemcentinib is a first-in-class, selective, orally bioavailable, AXL kinase inhibitor which is being evaluated as a therapy for solid tumours and myeloid malignancies in multiple phase II clinical trials. Increased levels of the plasma soluble, shed form of the AXL receptor (sAXL) upon bemcentinib exposure have been found across the clinical trial programme. The Phase I/II trial BGBC003 (NCT02488408) evaluates the anti-leukaemic effect of bemcentinib in patients with relapsed / refractory AML and int-2 and high-risk MDS. Methods Part A of the BGBC003 consisted of a dose escalation part per standard 3+3 design, followed by cohort expansion at the recommended phase 2 dose. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) at pre-dose and after one cycle of treatment. Gene expression analysis was carried out on RNA extracted from BM-MNCs by qPCR using TaqMan. The presence of phosphorylated AXL was measured using Western blotting. The TCRß repertoire was quantified by NGS of DNA isolated from PBMNCs using an Illumina MiSeq sequencer. TCRß genes and the IGH repertoire were analysed with BIOMED2-TCRß-A and -B and BIOMED2-FR1/-FR3 primer pools, respectively. Using genomic DNA as template, the amplicons were tagged with Illumina adapters and indices in two consecutive PCR reactions. Demultiplexing and FastQ formated data output was generated by the MiSeq reporter. Analysis of TCRß and IGH data was performed on a Microsoft Cloud using our in-house analysis pipeline Pippa. Results In total, 36 patients were enrolled in part A of the study: 27 male (75%), median age of 72 years old (51 - 85), 3 patients with MDS (8%), median of 2 lines of prior therapy (0 - 6). A loading dose of 400 mg on days one to three followed by 200 mg daily thereafter has been established as safe and recommended phase 2 dose. In patients who received treatment for at least 21 days (n=28), an ORR (CR/Cri/PR) of 25% (7/28) was observed. Median DoR was 63 days. In the subset of patients with available plasma measurements at screening (n=19), 12 showed low levels of plasma soluble shed AXL and an ORR of 58% (sAXL-low; 7 of 12 patients) was observed. No responses occurred in patients with high levels of sAXL at screening (sAXL-high; 0 out of 7). sAXL levels were correlated with exposure and one cycle of treatment with bemcentinib significantly increased sAXL protein levels, particularly in responders to treatment indicating on-target activity of the drug. Median PFS from the day of randomisation until evidence of disease progression (PD) per bone marrow assessment or discontinuation due to PD whichever occurred earlier, was 62 days overall (95% CI: 18 - 106 d), 124 days in sAXL-low patients and 63 days in sAXL-high patients, respectively. Adverse events were mostly gastrointestinal and mild or moderate in severity congruent with bemcentinib monotherapy being well-tolerated in this patient population. There were no grade 4 or 5 events. We observed a diversification of the TCR repertoire in the bone marrow in 75% of evaluable patients (6/8). In the peripheral blood we detected increased TCR diversification in 44% of evaluable patients (4/9). These data indicate that the contribution of the Gas6-AXL axis to immunosuppression might be particularly pronounced in the bone marrow microenvironment. This notion is in concordance with earlier data indicating a specific upregulation of Gas6 by bone marrow stroma cells upon paracrine interaction with AML cells leading to locally increased Gas6 levels. We also observed diversification of the BCR, however less frequently (bone marrow 42%, peripheral blood 11%). Conclusions Bemcentinib is well tolerated in relapsed / refractory MDS and AML patients and exhibits anti-leukaemic activity. Furthermore, we observed a diversification of the TCR repertoire particularly in the bone marrow thereby supporting a role of AXL as immune checkpoint. Patient benefit was correlated with the level of the plasma marker soluble AXL at screening. This predictive biomarker candidate warrants further exploration in larger cohorts and has potential for development as companion diagnostics to select patient populations more likely to respond to bemcentinib treatment. Disclosures Loges: BerGenBio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Paschka:Agios: Membership on an entity's Board of Directors or advisory committees; Astex: Membership on an entity's Board of Directors or advisory committees; Otsuka: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees, Travel support; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Bristol-Meyers Squibb: Other: Travel support, Speakers Bureau; Takeda: Other: Travel support; Jazz: Speakers Bureau; Sunesis: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Travel support; Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Travel support. Micklem:BerGenBio ASA: Employment, Equity Ownership, Patents & Royalties. Holt:BerGenBio ASA: Employment, Patents & Royalties. Brown:BerGenBio ASA: Employment, Equity Ownership, Patents & Royalties. Lorens:BerGenBio ASA: Employment, Equity Ownership, Patents & Royalties. Yule:BerGenBio ASA: Employment, Equity Ownership, Patents & Royalties. Fiedler:Amgen: Research Funding; GSO: Other: support for meeting attendance; Amgen: Other: support for meetíng attendance; Daiichi Sankyo: Other: support for meeting attendance; JAZZ Pharmaceuticals: Other: support for meeting attendance; Pfizer: Research Funding; Teva: Other: support for meeting attendance; Amgen: Patents & Royalties; Gilead: Other: support for meeting attendance; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; ARIAD/Incyte: Membership on an entity's Board of Directors or advisory committees, support for meeting attendance; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Cortes:novartis: Research Funding. Gjertsen:Alden Cancer Therapy 2: Equity Ownership; Alden Cancer Therapy 2: Patents & Royalties: Alden Cancer Therapy II patent application in relation to CryoIT trial.; Kinn Therapeutics: Equity Ownership; Seattle Genetics: Consultancy; Boehringer Ingelheim: Research Funding; BerGenBio: Consultancy; Alden Cancer Therapy 2: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Kinn Therapeutics: Membership on an entity's Board of Directors or advisory committees.
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Subodha Kumar, Rai G., Nagesha Parvathi, Rangegowda Suresh, Niruvappa Vinay, and Ittigi Vivekananda. "Efficacy and safety of povidone iodine with dimethyl sulfoxide vs 0.05% tretinoin in treatment of molluscum contagiosum: A randomized case control study." Our Dermatology Online 12, e (2021): e63-e63. http://dx.doi.org/10.7241/ourd.2021e.63.
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ABSTRACT Background: MC is an infection caused by a poxvirus. It is a self limiting condition, active therapy needed to prevent further spread, relieve symptoms, to prevent scarring and for cosmetic and social reasons. Methods: 40 patients were randomly divided into 2 groups; 20 each for Povidone Iodine with DMSO and 0.05% Tretinoin cream. The given medication was applied at bed time over molluscum lesions. The assessment of response and side effects were performed weekly for 4 weeks. Results: At the end of 4 weeks, the mean lesion count decreased from 6.45±3.60 SD to 4.25±3.76 SD and from 6.85±4.08 SD to 3.60±4.76 SD in patients treated with Povidone Iodine and 0.05% Tretinoin cream respectively. Conclusion: Tretinoin showed fast recovery, lesions were resolved before 4 weeks. In Povidone Iodine with DOMS showed delayed response and even some of lesion extended beyond 4 weeks but the side effect were less. Key words: MC-molluscum contagiosum.DMSO-dimethyl sulfoxide; SD-standard INTRODUCTION Molluscum contagiosum is an infection caused by a poxvirus (molluscum contagiosum virus). It is self-limited infectious dermatosis, frequent in paediatric population, sexually active adults, and immunocompromised individuals. It is caused by molluscum contagiosum virus (MCV) which is a virus of the Poxviridae family. MCV is transmitted mainly by direct contact with infected skin, which can be sexual, non-sexual, or autoinoculation [1].The lesions, known as Mollusca, are small, raised, dome shaped and usually pearly white, pink, or flesh-coloured with a dimple or pit in the centre. They often have a pearly appearance. They’re usually smooth and firm. In most people, the lesions range from about the size of a pinhead to as large as 2 to 5 millimetres in diameter. They may become itchy, sore, red, and/or swollen [2]. Mollusca may occur anywhere on the body including the face, neck, arms, legs, abdomen, and genital area, alone or in groups. The lesions are rarely found on the palms of the hands or the soles of the feet. The disease is common, with an estimated prevalence of 5–11%. The disease is rare under the age of 1 year, perhaps due to maternally transmitted immunity and a long incubation period. In hot countries where children are lightly dressed and in close contact with one another, spread within households is not uncommon. The age of peak incidence is reported as between 2 and 5 years. In cooler climates, however, spread within households is rare and infection may occur at a later age, perhaps correlated with the use of swimming pools and shared bathing facilities. A later incidence peak in young adults is attributable to sexual transmission with lesions more common in the genital area [2]. Treatment modalities that have been tried are caustic destruction by cantharidin, trichloroacetic acid, diluted liquefied phenol, Irritants like salicylic acid, adapalene, nitric oxide cream, potassium hydroxide, benzoyl peroxide, lemon myrtle oil, tea tree oil, Surgical irritation like cryotherapy, laser. Immunological modality like diphencyprone, imiquimod, interferon, cimetidine, intralesional immunotherapy and Surgical removal. All-trans-retinoic acid (tretinoin) is easily available as cream base thought to involve the induction of local irritation which damages the viral protein-lipid membrane [2]. Povidone iodine is used primarily in Dermatology as a surgical preparation, as it has been recognized as a broad-spectrum, resistance-free biocidal agent for many years. Povidone iodine also has a long track record of safety and tolerability given its extensive history of use in the operating room. Although incompletely understood, it is likely that free iodine poisons electron transport, inhibits cellular respiration, destabilizes membranes, inhibits protein synthesis, and denatures nucleic acids. Although Povidone iodine kills micro-organisms including bacteria, viruses, yeasts, molds, fungi, and protozoa, it has scarcely been used for purposes outside of skin asepsis in Dermatology. DMSO is currently FDA approved for the treatment of interstitial cystitis. DMSO is also a very effective pharmaceutical vehicle, greatly enhancing percutaneous penetration when used in combination with other substances [3]. Although it is a self limiting condition, a decision may be made in favor of active therapy to prevent further spread, relieve symptoms, to prevent scarring and for cosmetic and social reasons. The current treatment modalities include physical destruction of the lesion by curettage, cryosurgery or manual expression and topical application of caustic agents such as trichloroacetic acid, cantharidin, silver nitrate etc [4]. These therapeutic approaches have to be undertaken in a hospital setup and are not well tolerated by children owing to substantial pain and fear. In addition, these can also result in scarring and abscess formation [5]. Topical application of povidine iodine solution and 0.05% Tretinoin cream are two relatively painless modalities that have been used. Although tretinoin 0.05% cream which is commonly used, have shown different efficacy and safety profile in different studies, there are very few studies using povidone iodine and comparing the two. Hence this study was undertaken in view of comparing the safety and efficacy of the above two modalities in treating molluscum contagiosum. MATERIALS AND METHODS Double blinded randomized control study was conducted among 40 patients who attended Out Patient Department (OPD) of Dermatology Venereology and Leprosy Department, Hassan Institute of Medical Sciences Hassan, during the period of august 2019 to January 2020. Patients with Molluscum contagiosum more than 1 year of age and not taken any treatment for past 3 months were included in the study. Pregnant, lactating women, patients with more than 25 lesions, patients with lesion involving eyelid, patients with secondary infection and those who have history of hypersensitivity to Povidine iodine or Tretinoin were excluded from the study. 40 patients satisfying inclusion and exclusion criteria were recruited irrespective of sex, duration and response of disease to previous therapies. 40 patients were allocated randomly to group 1 and 2. In group 1, 20 patients were treated with povidone iodine with dimethyl sulfoxide and in group 2: 20 patients were treated with 0.05% tretinoin. A detailed history was obtained, and a thorough general, systemic and cutaneous examination was done. Information regarding age, sex, number of lesions, duration of illness, site of involvement, family history, history of atopy and previous treatment were collected. Patients were randomly divided into two groups; 20 each for povidone iodine with dimethyl sulfoxide solution and 0.05% Tretinoin cream group. Parents or guardians were advised to apply petroleum jelly around the lesions followed by application of the above medication to the centre of the lesion using a cotton swab, to be applied once every day at bed time for 4 weeks. If accidental spillage occurred, they were advised to wash the skin with water immediately. Parents were asked to report local (erythema, itching, burning, pain, erosion, crusting) and systemic (fever, flu like illness, diarrhoea, mylagia) side effects immediately. Follow up assessment was done every week for 4 weeks. At each follow up visit, clinical assessment of lesion, photographic assessment of lesion and any side effects were noted. Efficacy assessment was done by weekly examination of patient every week for 4 weeks. In each visit complete remission of number of lesions were noted in both groups and photographic assessment was done. Photographic assessment was done based on resolution of number of lesion in each follow up visit for 4 weeks. Any side effects present were noted at each visit. Statistical Analysis Data was entered in Microsoft Excel and SPSS software was used for the analysis. Results were expressed in percentages and proportions. Chi- square test, unpaired T- test, was used for analysis Ethics Statement Study was conducted after taking ethical committee clearance.
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Zhao, Hongwei, Hasaan Hayat, Xiaohong Ma, Daguang Fan, Ping Wang, and Anna Moore. "Molecular imaging and deep learning analysis of uMUC1 expression in response to chemotherapy in an orthotopic model of ovarian cancer." Scientific Reports 10, no. 1 (2020). http://dx.doi.org/10.1038/s41598-020-71890-2.
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Abstract Artificial Intelligence (AI) algorithms including deep learning have recently demonstrated remarkable progress in image-recognition tasks. Here, we utilized AI for monitoring the expression of underglycosylated mucin 1 (uMUC1) tumor antigen, a biomarker for ovarian cancer progression and response to therapy, using contrast-enhanced in vivo imaging. This was done using a dual-modal (magnetic resonance and near infrared optical imaging) uMUC1-specific probe (termed MN-EPPT) consisted of iron-oxide magnetic nanoparticles (MN) conjugated to a uMUC1-specific peptide (EPPT) and labeled with a near-infrared fluorescent dye, Cy5.5. In vitro studies performed in uMUC1-expressing human ovarian cancer cell line SKOV3/Luc and control uMUC1low ES-2 cells showed preferential uptake on the probe by the high expressor (n = 3, p < .05). A decrease in MN-EPPT uptake by SKOV3/Luc cells in vitro due to uMUC1 downregulation after docetaxel therapy was paralleled by in vivo imaging studies that showed a reduction in probe accumulation in the docetaxel treated group (n = 5, p < .05). The imaging data were analyzed using deep learning-enabled segmentation and quantification of the tumor region of interest (ROI) from raw input MRI sequences by applying AI algorithms including a blend of Convolutional Neural Networks (CNN) and Fully Connected Neural Networks. We believe that the algorithms used in this study have the potential to improve studying and monitoring cancer progression, amongst other diseases.
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Ogunade, Ibukun M., Godstime Taiwo, Zaira M. Estrada-Reyes, Y. Jiang, Andres A. Pech-Cervantes, and Sunday O. Peters. "Effects of a blend of mannan and glucan on growth performance, apparent nutrient digestibility, energy status and whole-blood immune gene expression of beef steers during a 42-d receiving period." Translational Animal Science, December 13, 2020. http://dx.doi.org/10.1093/tas/txaa226.
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Abstract We examined the effects of dietary supplementation of a blend of mannan and glucan on the growth performance, energy status, and whole-blood immune gene expression of newly weaned beef steers during a 42 d receiving period. Forty eight newly weaned Angus crossbred steers (2 d post-weaning; 199 ± 13 kg of initial BW) from a single source were stratified by BW and randomly assigned to 1 of 2 treatments: basal diet with no additive (CON; n = 24) or a basal diet top-dressed with 5 g of a blend of mannan and glucan (MANGLU; n = 24). Average daily gain (ADG) and feed efficiency (FE) from days 1 – 14, 15 – 42, and 1 – 42 were calculated from daily dry matter intake (DMI) and weekly BW. Blood samples were collected on days 0, 14, and 42 for measurement of plasma glucose and NEFA. Blood samples collected on days 14 and 42 were composited for each steer for untargeted carbonyl-metabolome analysis (measurement of carbonyl-containing metabolites). Expression of 84 immune-related genes was analyzed on blood samples collected on day 42. Beginning on days 37 to 42, total mixed ration, refusals, and fecal samples were collected once daily to determine apparent total tract digestibility of DM, CP, NDF, and ADF using indigestible NDF as an internal marker. Over the 42-d feeding trial, supplemental MANGLU tended to increase final BW (P = 0.07) and ADG (P = 0.06). Compared to CON, beef steers fed supplemental MANGLU had greater (P = 0.01) DMI during the first 14 d, greater DM digestibility (P = 0.03), and tended to have greater NDF digestibility (P = 0.09). No treatment effects (P &gt; 0.10) on plasma glucose and NEFA on d 14 and 42 were detected; however, carbonyl-metabolome analysis revealed increased (FDR ≤ 0.05) plasma concentrations of galactose and glyceraldehydes, and altered (FDR ≤ 0.05) concentrations of some microbiome-derived metabolites in beef steers fed MANGLU. Compared with CON, MANGLU increased (P ≤ 0.05) the expression of five immune-related genes involved in recognition of and mounting immune defense against microbial pathogens. In conclusion, the results of this study demonstrated that supplemental MANGLU enhances beef cattle immunocompetence and productivity during feedlot receiving period.
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Nwikpe, Barinaadaa John. "Tornumonkpe Distribution: Statistical Properties and Goodness of Fit." Asian Journal of Probability and Statistics, July 21, 2021, 12–22. http://dx.doi.org/10.9734/ajpas/2021/v14i130318.
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A new sole parameter probability distribution named the Tornumonkpe distribution has been derived in this paper. The new model is a blend of gamma (2, and gamma(3 distributions. The shape of its density for different values of the parameter has been shown. The mathematical expression for the moment generating function, the first three raw moments, the second and third moments about the mean, the distribution of order statistics, coefficient of variation and coefficient of skewness has been given. The parameter of the new distribution was estimated using the method of maximum likelihood. The goodness of fit of the Tornumonkpe distribution was established by fitting the distribution to three real life data sets. Using -2lnL, Bayesian Information Criterion (BIC), and Akaike Information Criterion(AIC) as criterial for selecting the best fitting model, it was revealed that the new distribution outperforms the one parameter exponential, Shanker and Amarendra distributions for the data sets used.
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Davydova, V., T. G. Bezhanishvili, M. E. Filatova, et al. "Expression of miRNA-21 level in hypertrophic cardiomyopathy patients with chronic heart failure and preserved left ventricular ejection fraction: results of a 6-year follow-up." European Heart Journal 41, Supplement_2 (2020). http://dx.doi.org/10.1093/ehjci/ehaa946.2088.
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Abstract Introduction Recently it is found that circulating miRNA-21 is associated with chronic heart failure (CHF) and ischemic heart disease. Its clinical significance in hypertrophic cardiomyopathy (HCM) and CHF with preserved left ventricular ejection fraction (LVEF) (≥50%) has to be investigated. Purpose The aim of this study was to analyze the expression of miRNA-21 in the peripheral blood of HCM patients and CHF with preserved LVEF (≥50%). Materials and methods From 2014 to 2019 years we examined 180 HCM patients. The study population consisted of 60 patients ≥19 years old (51.5 [36.2; 65.7]) with symptomatic HCM and CHF with preserved LVEF (≥50%). The diagnosis of HCM was established according to the guideline of the European society of cardiology on the diagnosis and treatment of HCM, 2014. The control group included 45 healthy donors without cardiovascular diseases and other severe pathologies, matched by age and sex with the studied group. Total RNA was extracted from plasma of patients. MiRNA-21 and reference RNA U6 cDNA was prepared based on StemLoop-technology. Expression was examined using semiquantitative RT-PCR protocol. Calculation of the relative gene expression level of miRNA-21 was done according to the standard procedure 2-ΔCt. IBM SPSS software package and Microsoft Excel 2010 were used for the statistical analysis of the collected data. Results The serum expression level of miRNA-21 in HCM patients (n=60) varied from 0.13 to 477.7 (4.92 [1.77; 13]) and was significantly higher than those in the control group (0.01 - 9.85 (0.84 [0.55; 1.23]), with statistically significant difference (p=0.001). The HCM group was divided according to CHF severity: I-II functional class (NYHA) (n=42) and III-IV functional class (NYHA) (n=18) subgroups. It was found a significant increase of expression microRNA-21 level in both subgroups HCM patients, compared with control group (p=0.001). The expression level of miRNA-21 also differed between HCM patients and CHF III-IV functional class (NYHA) vs those, who had CHF I-II functional class (NYHA) – 1.1–477.7 (13 [3.88; 41]) vs 0.1–119.4 (3.25 [1.41; 6.06]), respectively (p=0.003). In HCM patients and CHF III-IV functional class (NYHA) (n=18) the expression level of miRNA-21 positively correlated with LVEF (r=0.609; p&lt;0.05). Conclusion HCM patients with CHF III-IV functional class (NYHA) and preserved LVEF (≥50%) demonstrated high expression level of miRNA-21. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Almazov Federal Medical Research Centre, Saint-Petersburg, Russian Federation, Pavlov University, L'va Tolstogo str. 6-8, Saint Petersburg, Russian Federation
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Li, Meng M., Robin R. White, Le Luo Guan, Laura Harthan, and Mark D. Hanigan. "Metatranscriptomic analyses reveal ruminal pH regulates fiber degradation and fermentation by shifting the microbial community and gene expression of carbohydrate-active enzymes." Animal Microbiome 3, no. 1 (2021). http://dx.doi.org/10.1186/s42523-021-00092-6.
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Abstract Background Volatile fatty acids (VFA) generated from ruminal fermentation by microorganisms provide up to 75% of total metabolizable energy in ruminants. Ruminal pH is an important factor affecting the profile and production of VFA by shifting the microbial community. However, how ruminal pH affects the microbial community and its relationship with expression of genes encoding carbohydrate-active enzyme (CAZyme) for fiber degradation and fermentation are not well investigated. To fill in this knowledge gap, six cannulated Holstein heifers were subjected to a continuous 10-day intraruminal infusion of distilled water or a dilute blend of hydrochloric and phosphoric acids to achieve a pH reduction of 0.5 units in a cross-over design. RNA-seq based transcriptome profiling was performed using total RNA extracted from ruminal liquid and solid fractions collected on day 9 of each period, respectively. Results Metatranscriptomic analyses identified 19 bacterial phyla with 156 genera, 3 archaeal genera, 11 protozoal genera, and 97 CAZyme transcripts in sampled ruminal contents. Within these, 4 bacteria phyla (Proteobacteria, Firmicutes, Bacteroidetes, and Spirochaetes), 2 archaeal genera (Candidatus methanomethylophilus and Methanobrevibacter), and 5 protozoal genera (Entodinium, Polyplastron, Isotricha, Eudiplodinium, and Eremoplastron) were considered as the core active microbes, and genes encoding for cellulase, endo-1,4-beta- xylanase, amylase, and alpha-N-arabinofuranosidase were the most abundant CAZyme transcripts distributed in the rumen. Rumen microbiota is not equally distributed throughout the liquid and solid phases of rumen contents, and ruminal pH significantly affect microbial ecosystem, especially for the liquid fraction. In total, 21 bacterial genera, 4 protozoal genera, and 6 genes encoding CAZyme were regulated by ruminal pH. Metabolic pathways participated in glycolysis, pyruvate fermentation to acetate, lactate, and propanoate were downregulated by low pH in the liquid fraction. Conclusions The ruminal microbiome changed the expression of transcripts for biochemical pathways of fiber degradation and VFA production in response to reduced pH, and at least a portion of the shifts in transcripts was associated with altered microbial community structure.
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Carmichael-Wyatt, Remy N., Olivia N. Genther-Schroeder, and Stephanie L. Hansen. "The influence of dietary energy and zinc source and concentration on performance, trace mineral status, and gene expression of beef steers." Translational Animal Science 4, no. 4 (2020). http://dx.doi.org/10.1093/tas/txaa207.
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Abstract The objective of this study was to determine the effects of increased supplemental Zn from differing sources on growth performance of steers fed diets differing in net energy. Angus steers (n = 72, 324 ± 2.1 kg) with Genemax gain scores of 3, 4, or 5 were blocked by BW and stratified by Genemax gain score into 12 pens of 6 steers each for 158 d. Pens were randomly assigned to 1 of 3 Zn treatments (ZNTRT): 1) control (no supplemental Zn, analyzed 33 mg Zn/kg DM; CON); 2) inorganic Zn (CON + 120 mg supplemental Zn/kg DM as ZnSO4 for entire trial; INZN); or 3) 120 mg supplemental Zn/kg DM as Zn-amino acid complex (Availa-Zn; Zinpro, Eden Prairie, MN) for first 60 d, then a blend of ZnSO4 and Zn-AA complex (CON + 60 mg supplemental Zn/kg DM as ZnSO4 + 60 mg supplemental Zn/kg DM as Zn-amino acid complex) for the remainder of the trial (ZNBLD). Two dietary energy strategies (ENERGY) were formulated to reach ADG rates of 1) 1.6 kg/d (LE) or 2) 2.0 kg/d (HE) utilizing a 3 × 2 factorial arrangement (12 steers/treatment). All steers were fed LE for a 60 d growing period, then pens were randomly assigned to ENERGY treatments fed the remaining 91 d. Day 60 BW tended to be greater (P = 0.07) in steers receiving supplemental Zn vs. CON. Liver Cu was decreased in Zn supplemented steers vs. CON (P = 0.02). Liver Zn concentrations on d 56 did not differ for Zn vs. CON (P = 0.22) nor were there differences due to Zn source (P = 0.98). There were or tended to be ZNTRT × ENERGY effects for d 67–90 ADG and G:F (P ≤ 0.01), and d 122 BW and d 90–122 G:F (P ≤ 0.10) driven by improved performance for ZNBLD-HE over ZNBLD-LE, while ENERGY within CON and INZN did not differ. Day 90–122 ADG, overall ADG and overall G:F was greater (P ≤ 0.02) and d 67–90 G:F tended to be greater (P = 0.10) for HE vs. LE. No ZNTRT × ENERGY or ZNTRT effects were detected for HCW, REA, BF, KPH, MS, or YG (P ≥ 0.37) while HE increased HCW, BF, MS, and YG compared with LE (P ≤ 0.05). In the liver, ZNTRT affected d 97 MT1A expression (P = 0.03) where INZN was greater than ZNBLD or CON (P ≤ 0.02), while ZIP14 was unaffected due to ZNTRT, ENERGY, or the interaction (P ≥ 0.39). Supplying supplemental Zn as ZNBLD during the transition period appeared to improve performance measures, but no final performance advantages were noted due to increased supplemental Zn, regardless of source. Additionally, differences in liver MT1A expression may indicate differing post-absorptive metabolism between Zn sources.
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Costa, Carolina, Ramon Rizzieri, Gabriel Melo, et al. "Effects of fatty acid profile of supplements on intake, performance, carcass traits, meat characteristics, and meat sensorial analysis of feedlot Bos indicus bulls offered a high-concentrate diet." Translational Animal Science 4, no. 3 (2020). http://dx.doi.org/10.1093/tas/txaa142.
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Abstract This experiment was designed to evaluate the effects of lipid source and fatty acid (FA) profile on intake, performance, carcass characteristics, expression of enzymes, and sensorial analysis of Bos indicus animals offered a high-concentrate diet. On day 0, 96 noncastrated animals were blocked by initial body weight (400 ± 19.3 kg), randomly allocated to 1 of 24 pens (4 animals/pen), and pens were randomly assigned to receive: 1) control: basal diet composed of whole cottonseed and corn germ as lipid substrates (CONT; n = 6), 2) calcium salts of fatty acids (CSFA) of soybean: CSFA of soybean oil as replacement for whole cottonseed and corn germ (calcium salts of soybean oil [CSSO]; n = 6), 3) CSFA-Blend: CSFA of palm, cottonseed, and soybean oil as replacement for whole cottonseed and corn germ (calcium salts of vegetable oils [CSVO]; n = 6), and 4) Mix: basal diet containing whole cottonseed, corn germ, and CSVO (MIXT; n = 6). Experiment lasted 108 d and performance, ultrasound measurements, as well as carcass characteristics were evaluated. Additionally, meat FA profile, expression of enzymes involved in lipid metabolism, and sensorial analysis were evaluated. No treatment effects were observed on performance variables, ultrasound, and carcass traits (P ≥ 0.22), whereas animals receiving CONT had a greater intake of C10:0, C16:0, C16:1 trans-9, C18:1 cis-9, C18:2, C18:3, total FA, monounsatured FA (MUFA), and polyunsaturated FA (PUFA) vs. CSSO and MIXT (P &lt; 0.05). Conversely, intake ratios of saturated FA (SFA):MUFA and SFA:PUFA were all reduced for CONT vs. other treatments. Meat obtained from CONT animals had greater colorimetric (L*, a*, and b*) values vs. MIXT (P &lt; 0.01). On meat FA profile, CONT increased C18:0 vs. supplementation with calcium salts (P &lt; 0.02) and supplementation with CSSO yielded greater meat concentrations of C18:1 trans-10 and C18:2 CLA intermediates (P &lt; 0.01). Expression of SREBP-1, SCD, and LPL was downregulated for CSSO (P &lt; 0.05). For sensorial analysis, regular flavor was greater (P = 0.01) for CSSO vs. other treatments, but also greater aroma (P = 0.05) vs. CONT and CSVO. In summary, addition of different lipid sources with varying FA profiles into high-concentrate diets did not affect performance and carcass characteristics of B. indicus animals, but supplementation with calcium salts of soybean oil inhibited the mRNA expression of enzymes involved in lipid metabolism, whereas flavor and aroma were positively affected by this lipid source.
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Adeyemi, James A., David L. Harmon, D. M. Paulus Compart, and Ibukun M. Ogunade. "Effects of a blend of Saccharomyces cerevisiae-based direct-fed microbial and fermentation products in the diet of newly weaned beef steers: growth performance, whole-blood immune gene expression, serum biochemistry, and plasma metabolome1." Journal of Animal Science, October 30, 2019. http://dx.doi.org/10.1093/jas/skz308.
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Abstract We examined the effects of dietary supplementation of a Saccharomyces cerevisiae-based direct-fed microbial (DFM) on the growth performance, whole-blood immune gene expression, serum biochemistry, and plasma metabolome of newly weaned beef steers during a 42 d receiving period. Forty newly weaned Angus crossbred steers (7 d post-weaning; 210 ± 12 kg of BW; 180 ± 17 d of age) from a single source were stratified by BW and randomly assigned to 1 of 2 treatments: basal diet with no additive (CON; n = 20) or a basal diet top-dressed with 19 g of the DFM (PROB; n = 20). Daily DMI and weekly body weights were measured to calculate average daily gain (ADG) and feed efficiency (FE). Expression of 84 immune-related genes was analyzed on blood samples collected on days 21 and 42. Serum biochemical parameters and plasma metabolome were analyzed on days 0, 21, and 42. On day 40, fecal grab samples were collected for pH measurement. Compared with CON, dietary supplementation of PROB increased final body weight (P = 0.01) and ADG (1.42 vs. 1.23 kg; P = 0.04) over the 42 d feeding trial. There was a tendency for improved FE with PROB supplementation (P = 0.10). No treatment effect (P = 0.24) on DMI was observed. Supplementation with PROB increased (P ≤ 0.05) the concentrations of serum calcium, total protein, and albumin. Compared with CON, dietary supplementation with PROB increased (P ≤ 0.05) the expression of some immune-related genes involved in detecting pathogen-associated molecular patterns (such as TLR1, TLR2, and TLR6), T-cell differentiation (such as STAT6, ICAM1, RORC, TBX21, and CXCR3) and others such as TNF and CASP1, on day 21 and/or day 42. Conversely, IL-8 was upregulated (P = 0.01) in beef steers fed CON diet on day 21. Plasma untargeted plasma metabolome analysis revealed an increase (P ≤ 0.05) in the concentration of metabolites, 5-methylcytosine and indoleacrylic acid involved in protecting the animals against inflammation in steers fed PROB diet. There was a tendency for lower fecal pH in steers fed PROB diet (P = 0.08), a possible indication of increased hindgut fermentation. This study demonstrated that supplementation of PROB diet improved the performance, nutritional status, and health of newly weaned beef steers during a 42 d receiving period.
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Sasikumar, Keerthi, Silvin Hannibal, Volker F. Wendisch, and K. Madhavan Nampoothiri. "Production of Biopolyamide Precursors 5-Amino Valeric Acid and Putrescine From Rice Straw Hydrolysate by Engineered Corynebacterium glutamicum." Frontiers in Bioengineering and Biotechnology 9 (March 29, 2021). http://dx.doi.org/10.3389/fbioe.2021.635509.
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The non-proteinogenic amino acid 5-amino valeric acid (5-AVA) and the diamine putrescine are potential building blocks in the bio-polyamide industry. The production of 5-AVA and putrescine using engineered Corynebacterium glutamicum by the co-consumption of biomass-derived sugars is an attractive strategy and an alternative to their petrochemical synthesis. In our previous work, 5-AVA production from pure xylose by C. glutamicum was shown by heterologously expressing xylA from Xanthomonas campestris and xylB from C. glutamicum. Apart from this AVA Xyl culture, the heterologous expression of xylAXc and xylBCg was also carried out in a putrescine producing C. glutamicum to engineer a PUT Xyl strain. Even though, the pure glucose (40 g L–1) gave the maximum product yield by both the strains, the utilization of varying combinations of pure xylose and glucose by AVA Xyl and PUT Xyl in CGXII synthetic medium was initially validated. A blend of 25 g L–1 of glucose and 15 g L–1 of xylose in CGXII medium yielded 109 ± 2 mg L–1 putrescine and 874 ± 1 mg L–1 5-AVA after 72 h of fermentation. Subsequently, to demonstrate the utilization of biomass-derived sugars, the alkali (NaOH) pretreated-enzyme hydrolyzed rice straw containing a mixture of glucose (23.7 g L–1) and xylose (13.6 g L–1) was fermented by PUT Xyl and AVA Xyl to yield 91 ± 3 mg L–1 putrescine and 260 ± 2 mg L–1 5-AVA, respectively, after 72 h of fermentation. To the best of our knowledge, this is the first proof of concept report on the production of 5-AVA and putrescine using rice straw hydrolysate (RSH) as the raw material.