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  • Garner posted an update 7 months, 2 weeks ago

    These findings suggest that these impaired trafficking pathways may represent similar therapeutic targets in these classes of neurodegenerative disorders.Regulatory T cells (Tregs) are a small yet critical subset of CD4+ T cells, which have the role of maintaining immune homeostasis by, for example, regulating self-tolerance, tumor immunity, anti-microbial resistance, allergy and transplantation rejection. The suppressive mechanisms by which Tregs function are varied and pleiotropic. The ability of Tregs to maintain self-tolerance means they are critical for the control and prevention of autoimmune diseases. Irregularities in Treg function and number can result in loss of tolerance and autoimmune disease. Restoring immune homeostasis and tolerance through the promotion, activation or delivery of Tregs has emerged as a focus for therapies aimed at curing or controlling autoimmune diseases. Such therapies have focused on the Treg cell subset by using drugs to suppress T effector cells and promote Tregs. Other approaches have trialed inducing tolerance by administering the autoantigen via direct administration, by transient expression using a DNA vector, or by antigen-specific nanoparticles. More recently, cell-based therapies have been developed as an approach to directly or indirectly enhance Treg cell specificity, function and number. This can be achieved indirectly by transfer of tolerogenic dendritic cells, which have the potential to expand antigen-specific Treg cells. Treg cells can be directly administered to treat autoimmune disease by way of polyclonal Tregs or Tregs transduced with a receptor with high affinity for the target autoantigen, such as a high affinity T cell receptor (TCR) or a chimeric antigen receptor (CAR). This review will discuss the strategies being developed to redirect autoimmune responses to a state of immune tolerance, with the aim of the prevention or amelioration of autoimmune disease.Vitex doniana is a major but threatened economic plant collected as a leafy vegetable and fruit in West Africa. How the species withstands coppicing as an agricultural management practice was investigated in this research. MDL-28170 Three seedling vigor classes (10-25 mm, 25-30 mm, 30-40 mm) and two coppicing heights (20 and 40 cm) were compared to controls in eight replicates using a randomized complete block design. Mixed effect models were used to compare the effects of treatments on sprouting intensity, sprout growth, and biomass yield in the short (12 months) and medium term (three and five years). Results indicated that V. doniana is a fast-growing species, with heights between 2.72-7.73 m and diameter at breast height between 4.46-14.64 cm in five years. Vigorous (basal diameter > 30 mm) and shorter coppices (20 cm high) produced a higher number of sprouts. Although biomass yield was relatively higher on high coppices, the difference was not statistically significant. While a more severe harvesting regime was detrimental to plant growth, V. doniana can be managed to produce both vegetables and fuel wood in the medium term. These findings are significant for further improvement of the species, for food security, and climate resilience.Currently, the problem of the impact of climate change on the productivity of forest ecosystems and their carbon-depositing capacity is far from being solved. Therefore, this paper presents the models for the stand biomass of the two-needled subgenus’ (Pinus spp.) and the genus Picea spp.’s trends along the trans-Eurasian hydrothermal gradients, designed for pure stands in a number of 2110- and 870-sample plots with Pinus and Picea correspondingly. It was found that in the case of an increase in mean winter temperatures by 1 °C, pine and spruce respond by increasing the biomass of most components, and in the case of an increase in the annual sum of precipitation by 100 mm, the total, aboveground, stem and root biomasses of pine and spruce react the same way, but crown biomass reacts in the opposite way. Therefore, all identified trends are species-specific.The authors wish to make the following corrections to this paper […].Worldwide, the number of people with diabetes has quadrupled since 1980 reaching 422 million in 2014 (World Health Organization). This distressing rise in diabetes also affects pregnant women and thus, in regard to early programming of adult diseases, creates a vicious cycle of metabolic dysfunction passed from one generation to another. Metabolic diseases are complex and caused by the interplay between genetic and environmental factors. High-glucose exposure during in utero development, as observed with gestational diabetes mellitus (GDM), is an established risk factor for metabolic diseases. Despite intense efforts to better understand this phenomenon of early memory little is known about the molecular mechanisms associating early exposure to long-term diseases risk. However, evidence promotes glucose associated oxidative stress as one of the molecular mechanisms able to influence susceptibility to metabolic diseases. Thus, we decided here to further explore the relationship between early glucose exposure and cellular stress in the context of early development, and focus on the concept of glycemic memory, its consequences, and sexual dimorphic and epigenetic aspects.Pulmonary drug delivery represents an attractive, non-invasive administration option. In addition to locally acting drugs, molecules that are intended to produce systemic effects can be delivered via the pulmonary route. Several factors need to be considered in the context of delivering drugs to or via the lungs-in addition to the drug itself, its formulation into an appropriate inhalable dosage form of sufficient stability is critical. It is also essential that this formulation is paired with a suitable inhaler device, which generates an aerosol of a particle/droplet size that ensures deposition in the desired region of the respiratory tract. Lastly, the patient’s (patho-) physiology and inhalation manoeuvre are of importance. This Special Issue brings together recent advances in the areas of inhalation device testing, aerosol formulation development, use of in vitro and in silico models in pulmonary drug deposition and drug disposition studies, and pulmonary delivery of complex drugs, such as vaccines, antibiotics and peptides, to or via the lungs.

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