The potential for immunoglobulins and host defense peptides (HDPs) to reduce the use of antibiotics in animal production

Abstract Innate defense mechanisms are aimed at quickly containing and removing infectious microorganisms and involve local stromal and immune cell activation, neutrophil recruitment and activation and the induction of host defense peptides (defensins and cathelicidins), acute phase proteins and complement activation. As an alternative to antibiotics, innate immune mechanisms are highly relevant as they offer rapid general ways to, at least partially, protect against infections and enable the build-up of a sufficient adaptive immune response. This review describes two classes of promising alternatives to antibiotics based on components of the innate host defense. First we describe immunoglobulins applied to mimic the way in which they work in the newborn as locally acting broadly active defense molecules enforcing innate immunity barriers. Secondly, the potential of host defense peptides with different modes of action, used directly, induced in situ or used as vaccine adjuvants is described

Plant cell culture technology in the cosmetics and food industries : current state and future trends

The production of drugs, cosmetics, and food which are derived from plant cell and tissue cultures has a long tradition. The emerging trend of manufacturing cosmetics and food products in a natural and sustainable manner has brought a new wave in plant cell culture technology over the past 10 years. More than 50 products based on extracts from plant cell cultures have made their way into the cosmetics industry during this time, whereby the majority is produced with plant cell suspension cultures. In addition, the first plant cell culture-based food supplement ingredients, such as Echigena Plus and Teoside 10, are now produced at production scale. In this mini review, we discuss the reasons for and the characteristics as well as the challenges of plant cell culture-based productions for the cosmetics and food industries. It focuses on the current state of the art in this field. In addition, two examples of the latest developments in plant cell culture-based food production are presented, that is, superfood which boosts health and food that can be produced in the lab or at home

Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma

Fenretinide induces apoptosis in neuroblastoma by induction of reactive oxygen species (ROS). In this study, we investigated the role of mitochondria in fenretinide-induced cytotoxicity and ROS production in six neuroblastoma cell lines. ROS induction by fenretinide was of mitochondrial origin, demonstrated by detection of superoxide with MitoSOX, the scavenging effect of the mitochondrial antioxidant MitoQ and reduced ROS production in cells without a functional mitochondrial respiratory chain (Rho zero cells). In digitonin-permeabilized cells, a fenretinide concentration-dependent decrease in ATP synthesis and substrate oxidation was observed, reflecting inhibition of the mitochondrial respiratory chain. However, inhibition of the mitochondrial respiratory chain was not required for ROS production. Co-incubation of fenretinide with inhibitors of different complexes of the respiratory chain suggested that fenretinide-induced ROS production occurred via complex II. The cytotoxicity of fenretinide was exerted through the generation of mitochondrial ROS and, at higher concentrations, also through inhibition of the mitochondrial respiratory chain

Patients' perceived needs of osteoarthritis health information: A systematic scoping review

Background: Optimal management of osteoarthritis requires active patient participation. Understanding patients’ perceived health information needs is important in order to optimize health service delivery and health outcomes in osteoarthritis. We aimed to review the existing literature regarding patients’ perceived health information needs for OA. Methods: A systematic scoping review was performed of publications in MEDLINE, EMBASE, CINAHL and PsycINFO (1990–2016). Descriptive data regarding study design and methodology were extracted and risk of bias assessed. Aggregates of patients’ perceived needs of osteoarthritis health information were categorized. Results: 30 studies from 2876 were included: 16 qualitative, 11 quantitative and 3 mixed-methods studies. Three areas of perceived need emerged: (1) Need for clear communication: terms used were misunderstood or had unintended connotations. Patients wanted clear explanations. (2) Need for information from various sources: patients wanted accessible health professionals with specialist knowledge of arthritis. The Internet, whilst a source of information, was acknowledged to have dubious reliability. Print media, television, support groups, family and friends were utilised to fulfil diverse information needs. (3) Needs of information content: patients desired more information about diagnosis, prognosis, management and prevention. Conclusions: Patients desire more information regarding the diagnosis of osteoarthritis, its impact on daily life and its long-term prognosis. They want more information not only about pharmacological management options, but also non-pharmacological options to help them manage their symptoms. Also, patients wanted this information to be delivered in a clear manner from multiple sources of health information. To address these gaps, more effective communication strategies are required. The use of a variety of sources and modes of delivery may enable the provision of complementary material to provide information more successfully, resulting in better patient adherence to guidelines and improved health outcomes

Alternative processing of its precursor is related to miR319 decreasing in melon plants exposed to cold

[EN] miRNAs are fundamental endogenous regulators of gene expression in higher organisms. miRNAs modulate multiple biological processes in plants. Consequently, miRNA accumulation is strictly controlled through miRNA precursor accumulation and processing. Members of the miRNA319 family are ancient ribo-regulators that are essential for plant development and stress responses and exhibit an unusual biogenesis that is characterized by multiple processing of their precursors. The significance of the high conservation of these non-canonical biogenesis pathways remains unknown. Here, we analyze data obtained by massive sRNA sequencing and 5 ' - RACE to explore the accumulation and infer the processing of members of the miR319 family in melon plants exposed to adverse environmental conditions. Sequence data showed that miR319c was down regulated in response to low temperature. However, the level of its precursor was increased by cold, indicating that miR319c accumulation is not related to the stem loop levels. Furthermore, we found that a decrease in miR319c was inversely correlated with the stable accumulation of an alternative miRNA (#miR319c) derived from multiple processing of the miR319c precursor. Interestingly, the alternative accumulation of miR319c and #miR319c was associated with an additional and non-canonical partial cleavage of the miR319c precursor during its loop-to-base-processing. Analysis of the transcriptional activity showed that miR319c negatively regulated the accumulation of HY5 via TCP2 in melon plants exposed to cold, supporting its involvement in the low temperature signaling pathway associated with anthocyanin biosynthesis. Our results provide new insights regarding the versatility of plant miRNA processing and the mechanisms regulating them as well as the hypothetical mechanism for the response to cold-induced stress in melon, which is based on the alternative regulation of miRNA biogenesis.Bustamante-González, AJ.; Marques Romero, MC.; Sanz-Carbonell, A.; Mulet, JM.; Gomez, GG. (2018). Alternative processing of its precursor is related to miR319 decreasing in melon plants exposed to cold. Scientific Reports. 8:1-13. https://doi.org/10.1038/s41598-018-34012-7S1138Borges, F. & Martienssen, R. A. The expanding world of small RNAs in plants. Nat Rev Mol Cell Biol 16, 727–741 (2015).Shriram, V., Kumar, V., Devarumath, R. M., Khare, T. S. & Wani, S. H. MicroRNAs As Potential Targets for Abiotic Stress Tolerance in Plants. Front Plant Sci 7, 817 (2016).Xie, M., Zhang, S. & Yu, B. microRNA biogenesis, degradation and activity in plants. Cell Mol Life Sci 72, 87–99 (2015).Bologna, N. G., Schapire, A. L. & Palatnik, J. F. Processing of plant microRNA precursors. Brief Funct Genomics 12, 37–45 (2012).Achkar, N. P., Cambiagno, D. A. & Manavella, P. A. miRNA Biogenesis: A Dynamic Pathway. Trends Plant Sci 21, 1034–1044 (2016).Dong, Z., Han, M. H. & Fedoroff, N. The RNA-binding proteins HYL1 and SE promote accurate in vitro processing of pri-miRNA by DCL1. Proc Natl Acad Sci USA 105, 9970–9975 (2008).Bologna, N. G. et al. Multiple RNA recognition patterns during microRNA biogenesis in plants. Genome Research 23, 1675–1689 (2013).Baranauskė, S. et al. Functional mapping of the plant small RNA methyltransferase: HEN1 physically interacts with HYL1 and DICER-LIKE 1 proteins. Nucleic Acids Res 43, 2802–2812 (2015).Zhang, S., Liu, Y. & Yu, B. New insights into pri-miRNA processing and accumulation in plants. WIREs. RNA 6, 533–545 (2015).Ren, G. et al. Regulation of miRNA abundance by RNA binding protein TOUGH in Arabidopsis. Proc Natl Acad Sci USA 109, 12817–12821 (2012).Cuperus, J. T., Fahlgren, N. & Carrington, J. C. Evolution and functional diversification of MIRNA genes. Plant Cell 23, 431–442 (2011).Zhang, W. et al. Multiple distinct small RNAs originate from the same microRNA precursors. Genome Biol 11(8), r81 (2010).Addo-Quaye, C. et al. Sliced microRNA targets and precise loop-first processing of MIR319 hairpins revealed by analysis of the Physcomitrella patens degradome. RNA 15, 2112–2121 (2009).Axtell, M. J., Snyder, J. A. & Bartel, D. P. Common functions for diverse small RNAs of land plants. Plant Cell 19, 1750–1769 (2007).Bologna, N. G., Mateos, J. L., Bresso, E. G. & Palatnik, J. F. A loop-to-base processing mechanism underlies the biogenesis of plant microRNAs miR319 and miR159. EMBO J 28, 3646–3656 (2009).Li, Y., Li, C., Ding, G. & Jin, Y. Evolution of MIR159/319 microRNA genes and their post-transcriptional regulatory link to siRNA pathways. BMC Evol Biol 11, 122 (2011).Sobkowiak, L., Karlowski, W., Jarmolowski, A. & Szweykowska-Kulinska, Z. Non-Canonical Processing of Arabidopsis pri-miR319a/b/c Generates Additional microRNAs to Target One RAP2.12 mRNA Isoform. Front Plant Sci 3, 46 (2012).Achard, P., Herr, A., Baulcombe, D. C. & Harberd, N. P. Modulation of floral development by a gibberellin-regulated microRNA. Development 131, 3357–3365 (2004).Allen, R. S. et al. Genetic analysis reveals functional redundancy and the major target genes of the Arabidopsis miR159 family. Proc Natl Acad Sci USA 104, 16371–16376 (2007).Jones-Rhoades, M. W. & Bartel, D. P. Computational identification of plant microRNAs and their targets, including a stress-induced miRNA. Mol Cell 14, 787–799 (2004).Palatnik, J. F. et al. Control of leaf morphogenesis by microRNAs. Nature 425, 257–263 (2003).Wang, S. T. et al. MicroRNA319 positively regulates cold tolerance by targeting OsPCF6 and OsTCP21 in rice (Oryza sativa). PLoS One 9(3), e91357 (2014).Thiebaut, F. et al. Regulation of miR319 during cold stress in sugarcane. Plant Cell Environ 35, 502–512 (2012).Sunkar, R. & Zhu, J. K. Novel and stress-regulated microRNAs and other small RNAs from Arabidopsis. Plant Cell 16, 2001–2019 (2004).Chen, H. et al. A comparison of the low temperature transcriptomes of two tomato genotypes that differ in freezing tolerance: Solanum lycopersicum and Solanum habrochaites. BMC Plant Biol 15, 132 (2015).Garcia-Mas, J. et al. The genome of melon (Cucumis melo L.). Proc Natl Acad Sci USA 109, 11872–11877 (2012).Nuñez-Palenius, H. G. et al. Melon fruits: genetic diversity, physiology, and biotechnology features. Crit Rev Biotechnol 28, 13–55 (2008).Gonzalez-Ibeas, D. et al. Analysis of the melon (Cucumis melo) small RNAome by high-throughput pyrosequencing. BMC Genomics 12, 393 (2011).Herranz, M. C., Navarro, J. A., Sommen, E. & Pallas, V. Comparative analysis among the small RNA populations of source, sink and conductive tissues in two different plant-virus pathosystems. BMC Genomics 16, 117 (2015).Sattar, S. et al. Expression of small RNA in Aphis gossypii and its potential role in the resistance interaction with melon. PLoS One 7(11), e48579 (2012).Dai, X. & Zhao, P. X. psRNATarget: a plant small RNA target analysis server. Nucleic Acids Res. 39, W155–9 (2011).Palatnik, J. F. et al. Sequence and expression differences underlie functional specialization of Arabidopsis microRNAs miR159 and miR319. Dev Cell 13, 115–125 (2007).He, Z., Zhao, X., Kong, F., Zuo, Z. & Liu, X. TCP2 positively regulates HY5/HYH and photomorphogenesis in Arabidopsis. J Exp Bot 67, 775–785 (2016).Lau, O. S. & Deng, X. W. Plant hormone signaling lightens up: integrators of light and hormones. Curr Opin Plant Biol 13, 571–577 (2010).Oyama, T., Shimura, Y. & Okada, K. The Arabidopsis HY5 gene encodes a bZIP protein that regulates stimulus-induced development of root and hypocotyl. Genes Dev 11, 2983–2995 (1997).Ahmed, N. U., Park, J. I., Jung, H. J., Hur, Y. & Nou, I. S. Anthocyanin biosynthesis for cold and freezing stress tolerance and desirable color in Brassica rapa. Funct Integr Genomics 15, 383–394 (2015).Catalá, R., Medina, J. & Salinas, J. Integration of low temperature and light signaling during cold acclimation response in Arabidopsis. Proc Natl Acad Sci USA 108, 16475–16480 (2011).Schulz, E., Tohge, T., Zuther, E., Fernie, A. R. & Hincha, D. K. Natural variation in flavonol and anthocyanin metabolism during cold acclimation in Arabidopsis thaliana accessions. Plant Cell Environ 38, 1658–1672 (2015).Perea-Resa, C., Rodríguez-Milla, M. A., Iniesto, E., Rubio, V. & Salinas, J. Prefoldins Negatively Regulate Cold Acclimation in Arabidopsis thaliana by Promoting Nuclear Proteasome-Mediated HY5 Degradation. Mol Plant 10, 791–804 (2017).Solfanelli, C., Poggi, A., Loreti, E., Alpi, A. & Perata, P. Sucrose-Specific Induction of the Anthocyanin Biosynthetic Pathway in Arabidopsis. Plant Physiol 140, 637–646 (2006).Reis, R. S., Eamens, A. L. & Waterhouse, P. M. Missing Pieces in the Puzzle of Plant MicroRNAs. Trends Plant Sci 20, 721–728 (2015).Kumar, R. Role of microRNAs in biotic and abiotic stress responses in crop plants. Appl Biochem Biotech 174, 93–115 (2014).Ma, C., Burd, S. & Lers, A. miR408 is involved in abiotic stress responses in Arabidopsis. Plant J 84, 169–187 (2015).Song, L., Axtell, M. J. & Fedoroff, N. V. RNA secondary structural determinants of miRNA precursor processing in Arabidopsis. Curr Biol 20, 37–41 (2010).Bracken, C. P. et al. Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage. Nucleic Acids Res 39, 5658–5668 (2011).Gurtan, A. M., Lu, V., Bhutkar, A. & Sharp, P. A. In vivo structure-function analysis of human Dicer reveals directional processing of precursor miRNAs. RNA 18, 1116–1122 (2012).Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet Journal 17, 10–12 (2011).Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq-2. Genome Biol 15, 550 (2014).Robinson, M. D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol 11, 3–r25 (2010).Griffiths-Jones, S. miRBase: microRNA sequences and annotation. Current protocols in bioinformatics 12, 9 (2010).Li, H. et al. 1000 Genome Project Data Processing Subgroup The sequence alignment/map format & SAMtools. Bioinformatics 25, 2078–2079 (2009).Quinlan, A. & Hall, I. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25, 402–408 (2001).Llave, C., Xie, Z., Kasschau, K. D. & Carrington, J. C. Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science 297, 2053–2056 (2002).Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10, 3–r25 (2009)

Evolution of the avian β-defensin and cathelicidin genes

Background: β-defensins and cathelicidins are two families of cationic antimicrobial peptides (AMPs) with a broad range of antimicrobial activities that are key components of the innate immune system. Due to their important roles in host defense against rapidly evolving pathogens, the two gene families provide an ideal system for studying adaptive gene evolution. In this study we performed phylogenetic and selection analyses on β-defensins and cathelicidins from 53 avian species representing 32 orders to examine the evolutionary dynamics of these peptides in birds. Results and conclusions: Avian β-defensins are found in a gene cluster consisting of 13 subfamiles. Nine of these are conserved as one to one orthologs in all birds, while the others (AvBD1, AvBD3, AvBD7 and AvBD14) are more subject to gene duplication or pseudogenisation events in specific avian lineages. Avian cathelicidins are found in a gene cluster consisting of three subfamilies with species-specific duplications and gene loss. Evidence suggested that the propiece and mature peptide domains of avian cathelicidins are possibly co-evolving in such a way that the cationicity of the mature peptide is partially neutralised by the negative charge of the propiece prior to peptide secretion (further evidence obtained by repeating the analyses on primate cathelicidins). Negative selection (overall mean d

'Effects of a home-based bimodal lifestyle intervention in frail patients with end-stage liver disease awaiting orthotopic liver transplantation':study protocol of a non-randomised clinical trial

INTRODUCTION: Patients with end-stage liver disease awaiting orthotopic liver transplantation (OLT) are generally classified as frail due to disease-related malnutrition and a progressive decline in musculoskeletal and aerobic fitness, which is associated with poor pre-OLT, peri-OLT and post-OLT outcomes. However, frailty in these patients may be reversable with adequate exercise and nutritional interventions.METHODS AND ANALYSIS: Non-randomised clinical trial evaluating the effect of a home-based bimodal lifestyle programme in unfit patients with a preoperative oxygen uptake (VO2) at the ventilatory anaerobic threshold ≤13 mL/kg/min and/or VO2 at peak exercise ≤18 mL/kg/min listed for OLT at the University Medical Center Groningen (UMCG). The programme is patient tailored and comprises high-intensity interval and endurance training, and functional exercises three times per week, combined with nutritional support. Patients will go through two training periods, each lasting 6 weeks.The primary outcome of this study is the impact of the programme on patients' aerobic fitness after the first study period. Secondary outcomes include aerobic capacity after the second study period, changes in sarcopenia, anthropometry, functional mobility, perceived quality of life and fatigue, incidence of hepatic encephalopathy and microbiome composition. Moreover, number and reasons of intercurrent hospitalisations during the study and postoperative outcomes up to 12 months post OLT will be recorded. Finally, feasibility of the programme will be assessed by monitoring the participation rate and reasons for non-participation, number and severity of adverse events, and dropout rate and reasons for dropout.ETHICS AND DISSEMINATION: This study was approved by the Medical Research Ethics Committee of the UMCG (registration number NL83612.042.23, August 2023) and is registered in the Clinicaltrials.gov register (NCT05853484). Good Clinical Practice guidelines and the principles of the Declaration of Helsinki will be applied. Results of this study will be submitted for presentation at (inter)national congresses and publication in peer-reviewed journals.TRIAL REGISTRATION NUMBER: NCT05853484.</p