scholarly journals The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1155
Author(s):  
Olga Witkowska-Piłaszewicz ◽  
Rafał Pingwara ◽  
Anna Winnicka

Physical activity has an influence on a variety of processes in an athlete’s organism including the immune system. Unfortunately, there is a lack of studies regarding racehorse immune cells, especially when the horse model is compared to human exercise physiology. The aim of the study was to determine changes in immune cell proliferation, lymphocyte populations, and monocyte functionality in trained and untrained racehorses after exercise. In this study, field data were collected. The cells from 28 racehorses (14 untrained and 14 well-trained) were collected before and after exercise (800 m at a speed of about 800 m/min) and cultured for 4 days. The expression of CD4, CD8, FoxP3, CD14, MHCII, and CD5 in PBMC, and reactive oxygen species (ROS) production, as well as cell proliferation, were evaluated by flow cytometry. In addition, IL-1β, IL-4, IL-6, IL-10, IL-17, INF-γ, and TNF-α concentrations were evaluated by ELISA. The creation of an anti-inflammatory environment in well-trained horses was confirmed. In contrast, a pro-inflammatory reaction occurred in untrained horses after training. In conclusion, an anti-inflammatory state occurs in well-trained racehorses, which is an adaptational reaction to an increased workload during training.

2021 ◽  
Vol 2 (1) ◽  
pp. 100332
Author(s):  
Chirag Vasavda ◽  
Solomon H. Snyder ◽  
Bindu D. Paul

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 936
Author(s):  
Olga Witkowska-Piłaszewicz ◽  
Rafał Pingwara ◽  
Jarosław Szczepaniak ◽  
Anna Winnicka

Clenbuterol, the β2-adrenoceptor agonist, is gaining growing popularity because of its effects on weight loss (i.e., chemical liposuction). It is also popular in bodybuilding and professional sports, due to its effects that are similar to anabolic steroids. However, it is prohibited by anti-doping control. On the other hand, it is suggested that clenbuterol can inhibit the inflammatory process. The cells from 14 untrained and 14 well-trained race horses were collected after acute exercise and cultured with clenbuterol. The expressions of CD4, CD8, FoxP3, CD14, MHCII, and CD5 in PBMC, and reactive oxygen species (ROS) production, as well as cell proliferation, were evaluated by flow cytometry. In addition, IL-1β, IL-4, IL-6, IL-10, IL-17, INF-γ and TNF-α concentrations were evaluated by ELISA. β2-adrenoceptor stimulation leads to enhanced anti-inflammatory properties in well-trained horses, as do low doses in untrained animals. In contrast, higher clenbuterol doses create a pro-inflammatory environment in inexperienced horses. In conclusion, β2-adrenoceptor stimulation leads to a biphasic response. In addition, the immune cells are more sensitive to drug abuse in inexperienced individuals under physical training.


Nanomedicine ◽  
2021 ◽  
Author(s):  
Muktashree Saha ◽  
Anil P  Bidkar ◽  
Siddhartha S  Ghosh

Aim: The primary aim of this study was to develop biomimetic nanocarriers for specific homologous targeting of the anticancer drugs ammonium pyrrolidine dithiocarbamate (PDTC) and doxorubicin. Methods: Membranous nanovesicles were synthesized from a breast cancer cell line (MCF7) by syringe extrusion process and were loaded with PDTC and doxorubicin. Besides their abilities for self-homing, the drug loaded nanovesicles showed anti-cell proliferative effects via the generation of reactive oxygen species. Results: The nanovesicles demonstrated efficient internalization via homologous targeting. Delivery of PDTC showed a higher killing effect for homologous cell targeting than other cell types. Experimental results demonstrated increased antiproliferative potency of PDTC, which induced apoptosis via reactive oxygen species generation. Conclusion: The developed membrane-derived nanocarrier is an attractive biocompatible system for ex vivo targeted drug delivery.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi37-vi37
Author(s):  
Gabrielle Price ◽  
Daniel Rivera ◽  
Alexandros Bouras ◽  
Constantinos Hadjipanayis

Abstract Diffuse midline gliomas (DMGs) are highly invasive, unresectable tumors in children. To date, there is no effective treatment for DMGs. Fractionated radiotherapy (RT), currently the standard of care, has provided limited disease control. Current obstacles to treatment include the blood brain barrier (BBB) that limits systemic drug delivery, tumor therapy resistance, and brainstem infiltration. Given the unmet need for more effective DMG treatments, photodynamic therapy (PDT), with the precursor photosensitizing agent 5-aminolevulinic acid (5-ALA), is an oncologic treatment that holds promise. 5-ALA PDT of tumors occurs by targeting tumor cells that accumulate the 5-ALA metabolite, protoporphyrin IX (PPIX), with 635 nm light to create deadly reactive oxygen species (ROS). We explore the synergism of 5-ALA PDT with the MEK inhibitor, trametinib, since the RAS/MEK signaling pathway regulates tumor cell proliferation and survival and has been shown to therapeutically enhance PDT in select tumor models. We demonstrated that sub-micromolar levels of 5-ALA PDT and nanomolar levels of trametinib successfully decrease cell proliferation and induce apoptosis in multiple DMG cell lines. Cell viability assays revealed that drug response differs based on the histone mutation (H3.1 or H3.3) of the line. Mechanisms of decreased cell survival involves the generation of reactive oxygen species that induces programmed cell death. Through the use of a DMG genetically engineered mouse model, we also found 5-ALA PDT to induce apoptosis in vivo. The synergistic effects of MEK inhibition and 5-ALA PDT in vitro and apoptotic effects of 5-ALA PDT in vivo, highlights the potential therapeutic efficacy of this treatment modality.


2009 ◽  
Vol 2 (5) ◽  
pp. 317-321 ◽  
Author(s):  
Camila Armond Isoni ◽  
Érica Abreu Borges ◽  
Clara Araújo Veloso ◽  
Rafael Teixeira Mattos ◽  
Miriam Martins Chaves ◽  
...  

Peripheral blood mononuclear cells (PBMNC) from patients with type 2 diabetes (DM2) have generated higher levels of reactive oxygen species (ROS) that were higher than those in cells from healthy individuals. In the presence of a cAMP-elevating agent, ROS production was significantly activated in PBMNC from DM2 patients but it was inhibited in cells from healthy subjects. Higher levels of IL-6 has been detected in the supernatant of PBMNC cultures from DM2 patients in comparison with healthy controls. When cells were cultured in the presence of a cAMP-elevating agent, the level of IL-6 decreased has by 46% in the supernatant of PBMNC from DM2 patients but it remained unaltered in controls. No correlations between ROS and IL-6 levels in PBMNC from DM2 patients or controls have been observed. Secretions of IL-4 or IFN by PBMNC from patients or controls have not been affected by the elevation of cAMP. cAMP elevating agents have activated the production of harmful reactive oxidant down modulated IL-6 secretion by these cells from DM2 patients, suggesting an alteration in the metabolic response possibly due to hyperglicemia. The results suggest that cAMP may play an important role in the pathogenesis of diabetes.


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