scholarly journals A bioartificial kidney device with polarized secretion of immune modulators

2018 ◽  
Vol 12 (7) ◽  
pp. 1670-1678 ◽  
Author(s):  
N. V. Chevtchik ◽  
M. Mihajlovic ◽  
M. Fedecostante ◽  
L. Bolhuis-Versteeg ◽  
J. Sastre Toraño ◽  
...  
Author(s):  
Greg V. Martin ◽  
Ann L. Hubbard

The microtubule (MT) cytoskeleton is necessary for many of the polarized functions of hepatocytes. Among the functions dependent on the MT-based cytoskeleton are polarized secretion of proteins, delivery of endocytosed material to lysosomes, and transcytosis of integral plasma membrane (PM) proteins. Although microtubules have been shown to be crucial to the establishment and maintenance of functional and structural polarization in the hepatocyte, little is known about the architecture of the hepatocyte MT cytoskeleton in vivo, particularly with regard to its relationship to PM domains and membranous organelles. Using an in situ extraction technique that preserves both microtubules and cellular membranes, we have developed a protocol for immunofluorescent co-localization of cytoskeletal elements and integral membrane proteins within 20 µm cryosections of fixed rat liver. Computer-aided 3D reconstruction of multi-spectral confocal microscope images was used to visualize the spatial relationships among the MT cytoskeleton, PM domains and intracellular organelles.


2020 ◽  
Vol 04 (04) ◽  
pp. 369-372
Author(s):  
Paul B. Romesser ◽  
Christopher H. Crane

AbstractEvasion of immune recognition is a hallmark of cancer that facilitates tumorigenesis, maintenance, and progression. Systemic immune activation can incite tumor recognition and stimulate potent antitumor responses. While the concept of antitumor immunity is not new, there is renewed interest in tumor immunology given the clinical success of immune modulators in a wide range of cancer subtypes over the past decade. One particularly interesting, yet exceedingly rare phenomenon, is the abscopal response, characterized by a potent systemic antitumor response following localized tumor irradiation presumably attributed to reactivation of antitumor immunity.


Author(s):  
Oleg Melnikov ◽  
Diana Zabolotnaya ◽  
Alexander Bredun ◽  
Bogdan Bil ◽  
Oksana Rylska ◽  
...  

Introduction: In recently ears factors of innate immunity both cellular and humoral have been paid considerable attention as they are a protective barrier of a fast response and that is why they are largely concentrated at the intersection of the digestive tract and airways. The data concerning the activity level of factors of innate immunity in the upper airways affected by nonspecific inflammatory processes is insufficient and sparse and therefore the purpose of this research was to study the content of humoral factors of innate immunity in the oropharyngeal secretion (ORS) of patients with chronic infectious inflammatory diseases of the upper airways in remission. Materials and Methods: There was an examination of 16 patients with chronic rhinosinusitis (CRS) of bacterial genesis (15-40 years old), 12 patients with rhinopharyngitis of post-viral genesis (8-16 years old), 12 people with scleroma from 30 tо 52 years of age (atrophic form), 10 patients with chronic tonsillitis in remission (from 10 to 33 years of age) and 11 patients of a control group (practically healthy donors from 12 tо 40 years of age). The content of MIP-1b, defensin-1β, lactoferrin, lysozyme, α-interferon was studied in the nonstimulated OPS. Statistics were carried out using Mann-Whitney U-test. Results: The greatest number of deviations in the decrease in the content of the examined nonspecific protective factors was found in cases of scleroma, chronic tonsillitis and chronic rhinosinusitis (p<0,05). The lack of protective humoral factors of innate immunity can be evidence of local immunodeficiency even in remission, which is a pathophysiological component of the maintenance of chronic inflammation. Conclusion: The decrease int he quantitative composition of factors of innate immunity in the oropharyngeal secretion of patients with chronic infectious inflammatory diseases of the airways is an objective ground not only for a replacement therapy, but also for the use of immune response modifiers from photo-immune modulators to “genuine immune modulators” controlling the state of the factors of both innate immunity and immunoglobulins, primarily of secretory type, the level and functionality of various groups of immunocompetent and accessory cells.


2021 ◽  
Vol 9 (7) ◽  
pp. 1415
Author(s):  
Sonia Laneri ◽  
Mariarita Brancaccio ◽  
Cristina Mennitti ◽  
Margherita G. De Biasi ◽  
Maria Elena Pero ◽  
...  

Antimicrobial peptides (AMPs), α- and β-defensins, possess antiviral properties. These AMPs achieve viral inhibition through different mechanisms of action. For example, they can: (i) bind directly to virions; (ii) bind to and modulate host cell-surface receptors, disrupting intracellular signaling; (iii) function as chemokines to augment and alter adaptive immune responses. Given their antiviral properties and the fact that the development of an effective coronavirus disease 2019 (COVID-19) treatment is an urgent public health priority, they and their derivatives are being explored as potential therapies against COVID-19. These explorations using various strategies, range from their direct interaction with the virus to using them as vaccine adjuvants. However, AMPs do not work in isolation, specifically in their role as potent immune modulators, where they interact with toll-like receptors (TLRs) and chemokine receptors. Both of these receptors have been shown to play roles in COVID-19 pathogenesis. In addition, it is known that a healthy lifestyle accompanied by controlled physical activity can represent a natural weapon against COVID-19. In competitive athletes, an increase in serum defensins has been shown to function as self-protection from the attack of microorganisms, consequently a controlled physical activity could act as a support to any therapies in fighting COVID-19. Therefore, including information on all these players’ interactions would produce a complete picture of AMP-based therapies’ response.


2021 ◽  
Vol 8 (7) ◽  
pp. 130
Author(s):  
Simona Sagona ◽  
Baldassare Fronte ◽  
Francesca Coppola ◽  
Elena Tafi ◽  
Matteo Giusti ◽  
...  

β-glucans can activate the animal innate immune system by acting as immune-modulators and inducing various stimulatory effects. The aim of this study was to investigate the effect of 1,3-1,6 β-glucans administered orally for 96 h on Apis mellifera workers (newly emerged and nurse bees). β-glucans were included in honey and syrup. Survival rate and phenoloxidase activity were measured. In both newly emerged and nurse bees, β-glucans supplementation did not affect survival rate (p > 0.05). Conversely, phenoloxidase activity was higher in both newly emerged bees (p = 0.048) and nurse bees (p = 0.014) fed with a honey diet enriched with β-glucans compared to those fed with only honey. In both the newly emerged and nurse bees, no statistical differences in phenoloxidase activity were recorded between the group fed with a syrup-based diet enriched with β-glucans and the control group (p > 0.05). The absence of significant variation in survival suggests that the potential negative effect of β-glucans in healthy bees could be mitigated by their metabolism. Conversely, the inclusion of β-glucans in a honey-based diet determined an increase of phenoloxidase activity, suggesting that the effect of β-glucan inclusion in the diet of healthy bees on phenoloxidase activity could be linked to the type of base-diet. Further investigations on β-glucans metabolism in bees, on molecular mechanism of phenoloxidase activation by 1,3-1,6 β-glucans, and relative thresholds are desirable. Moreover, investigation on the combined action of honey and β-glucans on phenoloxidase activity are needed.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan H. Trager ◽  
Emanuelle Rizk ◽  
Sharon Rose ◽  
Kuixi Zhu ◽  
Branden Lau ◽  
...  

AbstractThe presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p < 0.0001). Post-imiquimod therapy, levels of CDK1, CXCL13, IL1B, GADPH, TTK, ILF3, EWSR1, BIRC5, PLAUR, ISG20, and C1QBP were significantly lower (adjusted p < 0.05). Complete responders (CR) exhibited a distinct pattern of inflammatory gene expression pre-treatment relative to incomplete responders (IR), with alterations in 15 inflammatory pathways (p < 0.05) reflecting differential expression of 103 genes (p < 0.05). Presence of adverse effects was associated with improved treatment response. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treament may play a part in regression of AKs. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy.


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