scholarly journals Development and Physiological Functions of the Lymphatic System - Insights from Genetic Studies of Lymphedema

2021 ◽  
Author(s):  
Silvia Martin-Almedina ◽  
Peter Mortimer ◽  
Pia Ostergaard
Keyword(s):  
Lymphatic System ◽  
Imaging Techniques ◽  
The Body ◽  
Genetic Studies ◽  
Disease Mechanisms ◽  
Primary Lymphedema ◽  
And Function ◽  
The Impact

Primary lymphedema is a long-term (chronic) condition characterized by tissue lymph retention and swelling that can affect any part of the body, although it usually develops in the arms or legs. Due to the relevant contribution of the lymphatic system to human physiology, while this review mainly focusses on the clinical and physiological aspects related to the regulation of fluid homeostasis and edema, clinicians need to know that the impact of lymphatic dysfunction with a genetic origin can be wide ranging. Lymphatic gene dysfunction can affect immune function so leading to infection; it can influence cancer development and spread; and it can determine fat transport so impacting on nutrition and obesity. Genetic studies and the development of imaging techniques for the assessment of lymphatic function have enabled the recognition of primary lymphedema as a heterogenic condition in terms of genetic causes and disease mechanisms. In this review, the known biological function of several genes crucial to the development and function of the lymphatic system are used as a basis for understanding normal lymphatic biology. The disease conditions originating from mutations in these genes are discussed together with a detailed clinical description of the phenotype and the up-to-date knowledge in terms of disease mechanisms acquired from in vitro and in vivo research models.

scholarly journals Bovine sperm-oviduct interactions are characterized by specific sperm behaviour, ultrastructure and tubal reactions which are impacted by sex sorting

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Miguel Camara Pirez ◽  
Heather Steele ◽  
Sven Reese ◽  
Sabine Kölle
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Sperm Binding ◽  
Tail Movement ◽  
Bovine Spermatozoa ◽  
Sperm Reservoir ◽  
And Function ◽  
The Impact

Abstract To date sperm-oviduct interactions have largely been investigated under in vitro conditions. Therefore we set out to characterize the behaviour of bovine spermatozoa within the sperm reservoir under near in vivo conditions and in real-time using a novel live cell imaging technology and a newly established fluorescent sperm binding assay. Sperm structure and tubal reactions after sperm binding were analysed using scanning and transmission electron microscopy and histochemistry. As a model to specify the impact of stress on sperm-oviduct interactions, frozen-thawed conventional and sex-sorted spermatozoa from the same bulls (n = 7) were co-incubated with oviducts obtained from cows immediately after slaughter. Our studies revealed that within the oviductal sperm reservoir agile (bound at a tangential angle of about 30°, actively beating undulating tail), lagging (bound at a lower angle, reduced tail movement), immotile (absence of tail movement) and hyperactivated (whip-like movement of tail) spermatozoa occur, the prevalence of which changes in a time-dependent pattern. After formation of the sperm reservoir, tubal ciliary beat frequency is significantly increased (p = 0.022) and the epithelial cells show increased activity of endoplasmic reticula. After sex sorting, spermatozoa occasionally display abnormal movement patterns characterized by a 360° rotating head and tail. Sperm binding in the oviduct is significantly reduced (p = 0.008) following sexing. Sex-sorted spermatozoa reveal deformations in the head, sharp bends in the tail and a significantly increased prevalence of damaged mitochondria (p < 0.001). Our results imply that the oviductal cells specifically react to the binding of spermatozoa, maintaining sperm survival within the tubal reservoir. The sex-sorting process, which is associated with mechanical, chemical and time stress, impacts sperm binding to the oviduct and mitochondrial integrity affecting sperm motility and function.

scholarly journals IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2409-2414 ◽  
Author(s):  
Mojgan Ahmadzadeh ◽  
Steven A. Rosenberg
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Interleukin 2 ◽  
Selective Inhibition ◽  
High Dose ◽  
Protein Levels ◽  
And Function ◽  
The Impact

Abstract Interleukin-2 (IL-2) is historically known as a T-cell growth factor. Accumulating evidence from knockout mice suggests that IL-2 is crucial for the homeostasis and function of CD4+CD25+ regulatory T cells in vivo. However, the impact of administered IL-2 in an immune intact host has not been studied in rodents or humans. Here, we studied the impact of IL-2 administration on the frequency and function of human CD4+CD25hi T cells in immune intact patients with melanoma or renal cancer. We found that the frequency of CD4+CD25hi T cells was significantly increased after IL-2 treatment, and these cells expressed phenotypic markers associated with regulatory T cells. In addition, both transcript and protein levels of Foxp3, a transcription factor exclusively expressed on regulatory T cells, were consistently increased in CD4 T cells following IL-2 treatment. Functional analysis of the increased number of CD4+CD25hi T cells revealed that this population exhibited potent suppressive activity in vitro. Collectively, our results demonstrate that administration of high-dose IL-2 increased the frequency of circulating CD4+CD25hi Foxp3+ regulatory T cells. Our findings suggest that selective inhibition of IL-2-mediated enhancement of regulatory T cells may improve the therapeutic effectiveness of IL-2 administration. (Blood. 2006;107:2409-2414)

scholarly journals Long term exposure of human gut microbiota with high and low emulsifier sensitivity to soy lecithin in M-SHIME model.

2021 ◽  
Author(s):  
Lisa Miclotte ◽  
Ellen De Paepe ◽  
Qiqiong Li ◽  
Andreja Rajkovic ◽  
John Van Camp ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Day Treatment ◽  
Treatment Phase ◽  
Microbial Composition ◽  
Soy Lecithin ◽  
Potential Health ◽  
And Function ◽  
The Impact

In the context of the potential health hazards related to food processing, dietary emulsifiers have been shown to alter the structure and function of the gut microbial community, both in vivo and in vitro. In mouse models, these emulsifier exposed gut microbiota were shown to contribute to gut inflammation. Several knowledge gaps remain to be addressed though. As such, the impact from a longer timeframe of exposure on the gut microbiota is not known and interindividual variability in microbiome response needs to be measured. To answer these research questions, in this study the faecal microbiota from two individuals, previously selected for high and low emulsifier sensitivity, were exposed to two concentrations of soy lecithin during a 7 day treatment phase in the dynamic mucosal simulator of the human intestinal microbial ecosystem (M-SHIME). The results showed mild effects from soy lecithin on the composition and functionality of these microbial communities, which depended on the original microbial composition. The effects also mostly levelled off after 3 days of exposure. The emulsifier sensitivity for which the microbiota were selected, was preserved. Some potentially concerning effects were also registered: butyrate levels, positively correlating with Faecalibacterium abundance, were lowered by soy lecithin. Also the abundance of the beneficial Bifidobacterium genus was lowered, while the abundance of the notorious unclassified Enterobacteriaceae was increased. Within the family of the unclassified Lachnospiraceae, several genera were either suppressed or stimulated. The effects that these microbial alterations would have on a living host is not yet certain, especially given the fact that large fractions of soy lecithins constituents can be absorbed. Nevertheless, choline and phosphatidylcholine, both primary and absorbable constituents of soy lecithin, have recently been linked to cardiovascular disease via the generation of TMA by the gut microbiota. Further studies that validate our findings and link them to potential health outcomes are thus justified.

Nanofiber Micropatterns for Controlled Release of Biomolecules

2011 ◽  
Author(s):  
Walter Bonani ◽  
Claudio Migliaresi ◽  
Wei Tan
Keyword(s):  
The Body ◽  
Biodegradable Materials ◽  
Signal Molecules ◽  
3 Dimensional ◽  
The Past ◽  
Direct Delivery ◽  
And Function ◽  
Vascular Formation

Essential to growing or regenerating 3-dimensional tissues is the formation of functional microcirculation that provides nutrients, oxygen and signal molecules for tissue survival and function regeneration. In the past decade, molecule-based microvascular formation has been achieved in vitro and in vivo. However, direct delivery of angiogenic molecules often results in malformed hyperpermeable microvessels, microvessels with low density. This can be attributed to the lack of effective molecule mechanisms that regulate vascular formation. More recent studies utilize biodegradable materials to control the delivery of biomolecules for vascularization of engineered or ischemic tissues, and exciting results have shown the importance of molecule kinetics to the vascular formation. Molecule delivery mechanisms that mimic precisely-regulated spatiotemporal signaling events during natural vascularization may be a possible way to improve or optimize the process. Hence, this study is designed to develop a new release system capable of degrading in the body and releasing biomolecules in a spatiotemporally controlled manner.

scholarly journals Hemoglobin stimulates vigorous growth of Streptococcus pneumoniae and shapes the pathogen's global transcriptome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fahmina Akhter ◽  
Edroyal Womack ◽  
Jorge E. Vidal ◽  
Yoann Le Breton ◽  
Kevin S. McIver ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Positive Influence ◽  
The Body ◽  
Host Proteins ◽  
Vigorous Growth ◽  
Cultivation In Vitro ◽  
The Impact ◽  
Heme Binding Protein

Abstract Streptococcus pneumoniae (Spn) must acquire iron from the host to establish infection. We examined the impact of hemoglobin, the largest iron reservoir in the body, on pneumococcal physiology. Supplementation with hemoglobin allowed Spn to resume growth in an iron-deplete medium. Pneumococcal growth with hemoglobin was unusually robust, exhibiting a prolonged logarithmic growth, higher biomass, and extended viability in both iron-deplete and standard medium. We observed the hemoglobin-dependent response in multiple serotypes, but not with other host proteins, free iron, or heme. Remarkably, hemoglobin induced a sizable transcriptome remodeling, effecting virulence and metabolism in particular genes facilitating host glycoconjugates use. Accordingly, Spn was more adapted to grow on the human α − 1 acid glycoprotein as a sugar source with hemoglobin. A mutant in the hemoglobin/heme-binding protein Spbhp-37 was impaired for growth on heme and hemoglobin iron. The mutant exhibited reduced growth and iron content when grown in THYB and hemoglobin. In summary, the data show that hemoglobin is highly beneficial for Spn cultivation in vitro and suggest that hemoglobin might drive the pathogen adaptation in vivo. The hemoglobin receptor, Spbhp-37, plays a role in mediating the positive influence of hemoglobin. These novel findings provide intriguing insights into pneumococcal interactions with its obligate human host.

scholarly journals Iodothyronine deiodinase structure and function: from ascidians to humans

2012 ◽  
Vol 215 (2) ◽  
pp. 189-206 ◽  
Author(s):  
Veerle M Darras ◽  
Stijn L J Van Herck
Keyword(s):  
Developmental Stages ◽  
The Body ◽  
Thyroid Status ◽  
Iodothyronine Deiodinase ◽  
Relative Contribution ◽  
Iodothyronine Deiodinases ◽  
Different Types ◽  
And Function ◽  
The Impact

Iodothyronine deiodinases are important mediators of thyroid hormone (TH) action. They are present in tissues throughout the body where they catalyse 3,5,3′-triiodothyronine (T3) production and degradation via, respectively, outer and inner ring deiodination. Three different types of iodothyronine deiodinases (D1, D2 and D3) have been identified in vertebrates from fish to mammals. They share several common characteristics, including a selenocysteine residue in their catalytic centre, but show also some type-specific differences. These specific characteristics seem very well conserved for D2 and D3, while D1 shows more evolutionary diversity related to itsKm, 6-n-propyl-2-thiouracil sensitivity and dependence on dithiothreitol as a cofactorin vitro. The three deiodinase types have an impact on systemic T3levels and they all contribute directly or indirectly to intracellular T3availability in different tissues. The relative contribution of each of them, however, varies amongst species, developmental stages and tissues. This is especially true for amphibians, where the impact of D1 may be minimal. D2 and D3 expression and activity respond to thyroid status in an opposite and conserved way, while the response of D1 is variable, especially in fish. Recently, a number of deiodinases have been cloned from lower chordates. Both urochordates and cephalochordates possess selenodeiodinases, although they cannot be classified in one of the three vertebrate types. In addition, the cephalochordate amphioxus also expresses a non-selenodeiodinase. Finally, deiodinase-like sequences have been identified in the genome of non-deuterostome organisms, suggesting that deiodination of externally derived THs may even be functionally relevant in a wide variety of invertebrates.

scholarly journals Artificial skin composites

2019 ◽  
Vol 73 (1) ◽  
pp. 51
Author(s):  
Agata Ładniak
Keyword(s):  
Wound Dressings ◽  
Skin Damage ◽  
Skin Substitutes ◽  
Significant Deterioration ◽  
Form And Function ◽  
Potential Applications ◽  
And Function ◽  
The Impact

<p>Skin injuries are a health problem and can lead to serious, significant deterioration in the quality of life and, consequently, even illness and disability. Therefore, after wounding, immediate regeneration of the tissue is necessary to avoid further complications and pathogenesis. Consequently, many wound healing strategies have been developed, leading to the progress in constructing of multifunctional tissue substitutes for the skin, biomembranes, scaffolds and intelligent dressings. The field of science focusing on the creation of the above-mentioned products is tissue engineering (TE). Its main goal is to find a system that is able to replace or be a model that perfectly mimics the form and function of the skin. Research carried out on such constructs is mainly based on the analysis of mechanical properties (porosity, elasticity), as well as the assessment of the impact of individual components on processes related to the formation of new tissue as cell proliferation and differentiation, proliferation, angiogenesis - through <em>in vivo</em> studies (using animal models: mice, New Zealand rabbits) and <em>in vitro</em> (most often using mouse fibroblasts - L929). Skin constructions may have potential applications as wound dressings or skin substitutes in cases of severe skin damage.</p>

scholarly journals Dorsoventral polarity directs cell responses to migration track geometries

2020 ◽  
Vol 6 (31) ◽  
pp. eaba6505
Author(s):  
Emily O. Wisniewski ◽  
Panagiotis Mistriotis ◽  
Kaustav Bera ◽  
Robert A. Law ◽  
Jitao Zhang ◽  
...  
Keyword(s):  
Imaging Techniques ◽  
Myosin Ii ◽  
Cross Sectional ◽  
Dorsoventral Polarity ◽  
Rhoa Activity ◽  
Cell Responses ◽  
Aspect Ratios ◽  
The Impact

How migrating cells differentially adapt and respond to extracellular track geometries remains unknown. Using intravital imaging, we demonstrate that invading cells exhibit dorsoventral (top-to-bottom) polarity in vivo. To investigate the impact of dorsoventral polarity on cell locomotion through different confining geometries, we fabricated microchannels of fixed cross-sectional area, albeit with distinct aspect ratios. Vertical confinement, exerted along the dorsoventral polarity axis, induces myosin II–dependent nuclear stiffening, which results in RhoA hyperactivation at the cell poles and slow bleb-based migration. In lateral confinement, directed perpendicularly to the dorsoventral polarity axis, the absence of perinuclear myosin II fails to increase nuclear stiffness. Hence, cells maintain basal RhoA activity and display faster mesenchymal migration. In summary, by integrating microfabrication, imaging techniques, and intravital microscopy, we demonstrate that dorsoventral polarity, observed in vivo and in vitro, directs cell responses in confinement by spatially tuning RhoA activity, which controls bleb-based versus mesenchymal migration.

Iodinated poly(p-dioxanone) as a facile platform for X-ray imaging of resorbable implantable medical devices

2020 ◽  
Vol 35 (1) ◽  
pp. 39-48
Author(s):  
Fan Zhao ◽  
Haiyan Xu ◽  
Wen Xue ◽  
Yan Li ◽  
Jing Sun ◽  
...  
Keyword(s):  
Medical Devices ◽  
Melt Spinning ◽  
Imaging Techniques ◽  
Fibrous Materials ◽  
Hybrid Fibers ◽  
Implantable Medical Devices ◽  
X Ray ◽  
The Impact

Currently, implantable fibrous medical devices still suffer from invisibility under current clinical imaging techniques. To address this problem, 2, 3, 5-triiodobenzoic acid (TIBA) was recruited as a contrast agent, and then a set of iodinated poly( p-dioxanone) (PPDO) fibers was fabricated via melt-spinning hybrid blends of PPDO with TIBA (PPDO/TIBA). The impact of TIBA content on the rheological behavior of blends was evaluated firstly. The physical, chemical, and thermal properties of PPDO/TIBA fibers were investigated accordingly by SEM, FTIR, DSC, and TGA. Moreover, the radiopaque property of PPDO/TIBA hybrid fibers as a potential radio-opacifying platform for medical devices was verified in vitro and in vivo. Finally, the accumulated release results of the hybrid fibers during in vitro degradation indicate the continual X-ray visibility of the hybrid fibers maintains for 22 days. This intriguing iodinated platform may pave the way for constructing fibrous materials with in-situ X-ray tracking property.

scholarly journals Weaning-associated feed deprivation stress causes microbiota disruptions in a novel mucin-containing in vitro model of the piglet colon (MPigut-IVM)

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Raphaële Gresse ◽  
Frédérique Chaucheyras-Durand ◽  
Sylvain Denis ◽  
Martin Beaumont ◽  
Tom Van de Wiele ◽  
...  
Keyword(s):  
Animal Experiments ◽  
Taxonomic Composition ◽  
Economic Losses ◽  
Strong Increase ◽  
Swine Industry ◽  
Feed Deprivation ◽  
And Function ◽  
The Impact

Abstract Background Risk factors for the etiology of post-weaning diarrhea, a major problem in swine industry associated with enormous economic losses, remain to be fully elucidated. In concordance with the ethical concerns raised by animal experiments, we developed a new in vitro model of the weaning piglet colon (MPigut-IVM) including a mucin bead compartment to reproduce the mucus surface from the gut to which gut microbes can adhere. Results Our results indicated that the MPigut-IVM is able to establish a representative piglet archaeal and bacterial colon microbiota in terms of taxonomic composition and function. The MPigut-IVM was consequently used to investigate the potential effects of feed deprivation, a common consequence of weaning in piglets, on the microbiota. The lack of nutrients in the MPigut-IVM led to an increased abundance of Prevotellaceae and Escherichia-Shigella and a decrease in Bacteroidiaceae and confirms previous in vivo findings. On top of a strong increase in redox potential, the feed deprivation stress induced modifications of microbial metabolite production such as a decrease in acetate and an increase in proportional valerate, isovalerate and isobutyrate production. Conclusions The MPigut-IVM is able to simulate luminal and mucosal piglet microbiota and represent an innovative tool for comparative studies to investigate the impact of weaning stressors on piglet microbiota. Besides, weaning-associated feed deprivation in piglets provokes disruptions of MPigut-IVM microbiota composition and functionality and could be implicated in the onset of post-weaning dysbiosis in piglets.

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