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Nanotechnological Approaches for Management of NeuroAIDS
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Divya Suares, Mohd Farooq Shaikh, Clara Fernandes
Several scientists have done modifications to the liposomal surface by using polymers such as PEG and thus minimized the loss of actives and enhance the systemic circulation time. On similar lines, HIV latency activators may be incorporated into liposomes for selective targeting to primary CD4+ cells thus minimizing bystander (unrelated) cell activation. Thus, Kovochich and co-workers (2011) developed liposomes (Lip-Bry-Nel) containing HIV latency activator (viz. bryostatin–2) and protease inhibitor (viz. nelfinavir) by thin film evaporation method providing nanoparticles of average size 219 nm. This hypothesis was demonstrated by the researchers using peripheral blood mononuclear cell (PBMC) culture wherein the response of Lip-Bry-Nel was compared with isotype control antibody-coated liposomes, confirming selective targeting.
Cellular Therapeutics: A Novel Modality with Great Therapeutic Potential
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
As indicated previously, the area that is capturing a lot of attention is CART cells. Currently, viral vectors (lentiviruses, gamma retrovirus) are used to modify the T cells, but these are very costly and represent a large portion of the COGS for CART cells. Furthermore, the use of other expensive raw materials (e.g., serum, albumin), the need for segregated manufacturing stations to ensure cross-contamination does not occur, and the high cost of quality control (QC) on the final product all impact the final COGS. Lastly, as these processes are highly labor- and clean room time-intensive, this increases COGS values further. With the allogeneic approach, there are additional costs such as the need for nucleic acid material to knock out certain genes to allow for administration of the therapeutic to non-HLA-matched patients. Additionally, the cost for procuring the starting cellular material (i.e., peripheral blood mononuclear cell (PBMCs) adds to the overall cost of the allogeneic drug. However, for allogeneic CARTs, this is counterbalanced by the fact that multiple doses can be produced for multiple patients from a single manufacturing run. This reduces QC, labor, and facility costs on a per-dose basis.
Biomaterials and Immune Response in Periodontics
Published in Nihal Engin Vrana, Biomaterials and Immune Response, 2018
Sivaraman Prakasam, Praveen Gajendrareddy, Christopher Louie, Clarence Lee, Luiz E. Bertassoni
The mechanism of immune activation by dental alloys is still under investigation. Metal ions and proteins possibly form stable bonds, becoming haptens with immunogenic potential. Au-Pd alloys seem to be a weaker allergen than Ni, Cr or Co in other alloys, and individuals who are sensitive to Ni are likely to be allergic to Pd.128In vitro studies suggest that human peripheral blood mononuclear cell (PBMC) sensitisation to Co, Cr, Pd and Au may result in a Th1- and Th2-type mixed cellular immune response.129 PBMC can increase the levels of interleukin synthesis (IL) in accordance to the type of metal. Contact with Co increases IL-2 and 13, Pd raises IL-2 and IL-4, Au promotes IL-13 and interferon gamma (IFN- γ release), and Ni is related to high levels of IL-2, IL-4, IL-13, IFN- γ.129 Patients with oral nickel exposure may present increased levels of cytokines such as IL-4, IFN- γ, IL-5 and IL-10, which are related to type I hypersensitivity and type V immune reaction.127 Dental cast alloys can activate human monocyte-derived dendritic cells by inducing IL-8 production.130 Also, it has been described that Ni, Co and Pd directly bind to the toll-like receptor 4 (TLR4)131,132 and Au binds to TLR3 commencing the maturation of antigen-presenting cells.133
Triethylene glycol dimethacrylate: adjuvant properties and effect on cytokine production
Published in Acta Biomaterialia Odontologica Scandinavica, 2018
Sara Alizadehgharib, Anna-Karin Östberg, Ulf Dahlgren
Fresh blood cells from eight healthy blood donors were obtained from Sahlgrenska University Hospital in Gothenburg, Sweden. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation using Ficoll-Paque Plus (GE Healthcare Bio-Sciences, Uppsala, Sweden). The cells were resuspended in PBS, centrifuged, and resuspended in Dulbecco’s Modified Eagle’s Medium (D-MEM) (Invitrogen, Lidingö, Sweden) that was supplemented with 5% heat-inactivated human AB serum (Sigma Chemical Co., St. Louis, MO), 100 U/mL of penicillin and 100 μg/mL of streptomycin (Invitrogen). Cell viability was determined by staining with 0.4% Trypan Blue (Sigma-Aldrich, Steinheim, Germany) and counted under a microscope using a Bürker chamber.
DNA damage in mononuclear cells following maximal exercise in sedentary and physically active lean and obese men
Published in European Journal of Sport Science, 2021
Alessandra Peres, Igor M. Da Silva, Maeli Santos, Ângela Beretta, Vanessa Moraes Andrade, Pedro R. T. RomãO, Gilson P. Dorneles
During acute exercise, peripheral blood mononuclear cells (PBMC) are exposed to several molecules, including cytokines, ROS, and hormones, that alters the cellular redox state and may activate cell death pathways (Fisher et al., 2011; Neubauer, Reichhold, Nersesyan, König, & Wagner, 2008). PBMC, which includes mainly lymphocytes and monocytes, are responsible for specialized immune activities, such as cell growth, surveillance, pathogen recognition, and cytokinesis (Sen, Kemppainen, & Orešič, 2018). Indeed, an increase in lymphocyte DNA damage, as well as lymphopenia, has been observed following exhaustive endurance exercise, which may be associated with the inflammatory response and low immune surveillance (Danese et al., 2017; Peres et al., 2018). In a literature review, Neubauer and coworkers (Neubauer et al., 2008) found no relationship between exercise-induced inflammatory response and the promotion of lymphocyte DNA damage, mainly due to the anti-inflammatory impact of moderate exercise in healthy individuals. On the other hand, a recent systematic review and meta-analysis study identified a substantial increase in DNA damage immediately after acute endurance exercise that remains significant at least 1 day after the bout (Tryfidou, McClean, Nikolaidis, & Davison, 2020). The relationship between exercise and DNA damage may be explained through the elevation of ROS production during acute bouts by increased activity of phagocytes or due to systemic and tissue metabolic events (Tryfidou et al., 2020). Although exercise-induced ROS can act as cellular signalling molecules for the induction of physiological adaptations, exacerbations of DNA damage may be detrimental for obese individuals (Peres et al., 2018).
Genotoxic effects induced by beta-myrcene following metabolism by liver HepG2/C3A human cells
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Juliana Botinhon Orlando, Brian Ogushi Silva, Camila Lehnhardt Pires-Cunha, Clélia Akiko Hiruma-Lima, Isabel O’Neill de Mascarenhas Gaivão, Edson Luis Maistro
Human peripheral blood mononuclear cells (PBMC) (non-metabolizing cells), collected from four healthy (two males and two females) non-smoking volunteers (18 to 27 years old), and the human hepatoma cell line (HepG2/C3A), displaying phase 1 and phase 2 enzymes (metabolizing cells) (Hewitt and Hewitt 2004), were handled according to recommendations of OECD 487 (2014). PBMC were isolated from blood by using Histopaque®-1077, following manufacturer instructions. Donors provided written consent for blood sampling. The Human Ethical Committee of the São Paulo State University (UNESP), in Marília town, Brazil, approved the present study on August 6, 2014 (protocol 1009/2014).