Dendritic Cell-Based Cancer Vaccines Santos, Patricia M; Butterfield, Lisa H
The Journal of immunology (1950),
01/2018, Letnik:
200, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Dendritic cells (DC) are specialized immune cells that play a critical role in promoting an immune response against Ags, which can include foreign pathogenic Ags and self-tumor Ags. DC are capable of ...boosting a memory T cell response but most importantly they are effective initiators of naive T cell responses. Many years of studies have focused on the use of DC vaccines against cancer to initiate and shape an antitumor-specific immune response and/or boost existing spontaneous antitumor T cell responses. In this study we give a brief overview of DC biology, function, and cellular subsets, and review the current status of the field of DC as cancer vaccines.
There has been a considerable increase on research of the ecological consequences of microplastics released into the environment, but only a handful of works have focused on the nano-sized particles ...of polymer-based materials. Though their presence has been difficult to adequately ascertain, due to the inherent technical difficulties for isolating and quantifying them, there is an overall consensus that these are not only present in the environment – either directly released or as the result of weathering of larger fragments – but that they also pose a significant threat to the environment and human health, as well. The reduced size of these particulates (<1μm) makes them susceptible of ingestion by organisms that are at the base of the food-chain. Moreover, the characteristic high surface area-to-volume ratio of nanoparticles may add to their potential hazardous effects, as other contaminants, such as persistent organic pollutants, could be adsorbed and undergo bioaccumulation and bioamplification phenomena.
In this review, we describe the most relevant sources of nanoplastics and offer some insights into their fate once released into the environment. Furthermore, we overview the most prominent effects of these small particulates, while identifying the key challenges scientists currently face in the research of nanoplastics in the environment. Lastly, we give a brief summary of the economic impacts of the pollution caused by plastic litter – a potential key source of nanoplastics – in the oceans, the most common destination of these contaminants.
Display omitted
•There has been a considerable increase of research on the fate o nanosized plastics.•These can pose a significant threat to both the environment and human health.•We reviewed their sources, fates and effects.•We identified the key challenges researchers face in this field.•Insights into the future of nanoplastics-related research are presented.
MicroRNAs (miRNAs) are short (approximately 22 nt) non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a ...wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform containing probes for mature miRNAs. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL) and 9 low-grade squamous intraepithelial lesion (LSIL) samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, deregulated miRNAs were identified in malignant and pre-malignant cervical tissues after tackling the high expression variability observed. We were also able to identify putative target genes of relevant candidate miRNAs. Our results show that miRNA expression shows natural variability among human samples, which complicates miRNA data profiling analysis. However, such expression noise can be filtered and does not prevent the identification of deregulated miRNAs that play a role in the malignant transformation of cervical squamous cells. Deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of this tumour type.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in ...response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor/interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.
Songbird species (order Passeriformes, suborder Oscines) are important models in various experimental fields spanning behavioural genomics to neurobiology. Although the genomes of some songbird ...species were sequenced recently, the chromosomal organization of these species is mostly unknown. Here we focused on the two most studied songbird species in neuroscience, the zebra finch (Taeniopygia guttata) and the canary (Serinus canaria). In order to clarify these issues and also to integrate chromosome data with their assembled genomes, we used classical and molecular cytogenetics in both zebra finch and canary to define their chromosomal homology, localization of heterochromatic blocks and distribution of rDNA clusters. We confirmed the same diploid number (2n = 80) in both species, as previously reported. FISH experiments confirmed the occurrence of multiple paracentric and pericentric inversions previously found in other species of Passeriformes, providing a cytogenetic signature for this order, and corroborating data from in silico analyses. Additionally, compared to other Passeriformes, we detected differences in the zebra finch karyotype concerning the morphology of some chromosomes, in the distribution of 5S rDNA clusters, and an inversion in chromosome 1.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). To enable the development of ...more efficacious therapies, we aim to study the heterogeneity, signatures of unique cell populations, and cell-cell interactions of non-immune and immune cell populations in 6 human papillomavirus (HPV)
and 12 HPV
HNSCC patient tumor and matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset of 134,606 cells, we show cell type-specific signatures associated with inflammation and HPV status, describe the negative prognostic value of fibroblasts with elastic differentiation specifically in the HPV
TME, predict therapeutically targetable checkpoint receptor-ligand interactions, and show that tumor-associated macrophages are dominant contributors of PD-L1 and other immune checkpoint ligands in the TME. We present a comprehensive single-cell view of cell-intrinsic mechanisms and cell-cell communication shaping the HNSCC microenvironment.
Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility ...that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior.
Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naïve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α.
Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naïve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals.
In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.
Microplastic contamination of aquatic environments has become an increasingly alarming problem. These, defined as particles <5 mm, are mostly formed due to the cracking and embrittlement of larger ...plastic particles. Recent reports show that the increasing presence of microplastics in the environment could have significant deleterious consequences over the health of marine organisms, but also across the food chain. Herein, we have studied the effects of artificial seawater on polyethylene (PE)-based beads by exposing them up to eight weeks to saltwater in stirred batch reactors in the dark and examined the structural and morphological changes these endured. Electron microscopy observations showed that artificial seawater induces severe microcracking of the pellets' surfaces. Additionally, Fourier transform infrared spectroscopy (FTIR) analyses evidenced the formation of oxidized groups whenever these particles were exposed to water and an increase in organic matter content of the waters in which the pellets were kept was evidenced by Raman spectroscopy. There were also noticeable consequences in the thermal stability of the polyethylene pellets, as determined by thermogravimetric studies (TGA). Furthermore, the parallel exposure of polyethylene pellets to UV radiation yielded less pronounced effects, thus underscoring its lower preponderance in the degradation of this material. These results highlight the importance of determining the mechanisms of degradation of microplastics in marine settings and what the implications may be for the environment. Overall, the herein presented results show that a relatively short period of time of accelerated exposure can yield quantifiable chemical and physical impacts on the structural and morphological characteristics of PE pellets.
The complexity of rainwater dissolved organic matter (DOM) and the large percentage considered uncharacterized has made it difficult to determine the role of rainwater DOM in regional and global ...carbon budgets. Recent studies have concentrated on determining the structural characteristics of the bulk DOM in rainwater, but a comparison between the structural characteristics of rainwater DOM from different seasons is lacking. In this work, DOM was extracted from rainwater collected in different seasons by a procedure based on adsorption onto DAX-8 resin and a comparison between the spectroscopic characteristics of extracted DOM was performed using UV–visible, excitation–emission matrix (EEM) fluorescence and 1H NMR spectroscopies. Similar structural characteristics were observed for extracted DOM from the different seasons: high content of aliphatic structures, hydroxy and alkoxy groups, carbonyl groups and unsaturated carbon atoms, and low content of aromatic structures when compared with aliphatic structures. The obtained results suggest a model of chemical structures for the extracted DOM from rainwater, as consisting mainly of aliphatic chains, with COOH, –CH2OH, –COCH3, or –CH3 terminal groups, and with only a minor aromatic component. Moreover, this study suggests that the DOM extracted from rainwater has higher aliphatic character and lower aromatic content than aquatic humic substances. Thus, the chemical characteristics of aquatic humic substances may not be good models for DOM extracted from rainwater.
► DOM was extracted from rainwater by a procedure based on adsorption onto DAX-8 resin. ► Extracted DOM was characterized by UV–visible, molecular fluorescence and 1H NMR. ► Similar structural characteristics were observed for DOM from the different seasons. ► High content of aliphatic structures, alkoxy groups, and unsaturated carbon atoms. ► Low content of aromatic structures when compared with aliphatic structures.
Display omitted
•Interest in pennyroyal essential oil (EO) has grown in the last decade.•There is a high diversity in pennyroyal EO composition.•Pennyroyal EO is an effective biocide against a wide ...range of pests.•Encapsulation or introduction in biofilms is of interest for other applications.
The widespread use of pesticides has made them into a frequent pollutant of soils and water. The usage of essential oils has gathered the attention of the scientific research community in the last decade as they present a reduced environmental impact compared to conventional pesticides and are equally or more effective in controlling pests in crops. Pennyroyal (Mentha pulegium) essential oil is of particular interest due to its traditional usage in plague/pest control. In fact, recent studies show that it is highly effective and presents a broad spectrum of action as a biocide, affecting bacteria, fungi, yeast, insects, acarines, parasites, nematodes, and plants. This is mainly due to the most common constituents of the essential oil, pulegone and menthone, which are known to have strong pesticidal and antioxidant properties. This review focus on summarizing and systematizing the composition and efficacy as a biocide of M. pulegium essential oils and the developments of the last decade regarding the usage of M. pulegium essential oil as an alternative to pesticides. Encapsulation and inclusion in biofilms are also mentioned as strategies to incorporate M. pulegium essential oil in applications associated with pharmaceutical and food industries.
PDF
