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Lipid Bubbles and Ultrasound for Drug Delivery
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Gene delivery has also been examined by co-injection of plasmid DNA with bubbles and combined with ultrasound exposure with the purpose of increasing the gene expression locally. In a study in our lab plasmids carrying the Interleukin-12 (IL-12) gene were used to treat tumours in mice. IL-12 is known to have immunomodulatory effects, affecting the immune response against cancer (Lu, 2017; Brunda, 1994). In our study IL-12 plasmid (pCMV-IL-12) was combined with bubbles injected locally before US exposure (Suzuki et al., 2010). This was compared to the same plasmid alone or with bubbles without US exposure or US but no bubbles. Also, the commercial transfection tool Lipofectamine 2000 (LF2000) was tested with pCMV-IL-12. The effect was evaluated by measuring tumour volume and the results showed a significant decrease of tumour growth with pCMV-IL-12, bubbles and ultrasound whereas the other groups did not affect tumour growth (Fig. 7.5). Further, the mechanism of the effect was investigated, and it was found that depletion of CD8+ T-cells effectively blocked the anti-tumour effect of the treatment showing the involvement of the immune system (Suzuki et al., 2010).
Mass spectrometry techniques for detection of COVID-19 viral and host proteins using naso-oropharyngeal swab and plasma
Published in Sanjeeva Srivastava, Multi-Pronged Omics Technologies to Understand COVID-19, 2022
Recently, MS-based proteomics techniques have been explored for the detection of both viral and host proteins. The list of host and viral proteins detected in swab samples using MS techniques are shown in Table 3.2. Nikolaev et al. identified around 1,500 proteins in the nasopharynx swabs using an untargeted LC-MS/MS approach, out of which nucleoprotein (P0DTC9) from SARS-CoV-2 was detected with high confidence (Nikolaev et al. 2020). Akgun et al., using nanoLC-MS, identified 17 statistically significant proteins out of a total of 207 host proteins detected in the swab samples. The significant proteins such as Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were identified to be linked to alteration in the innate immune system, specifically via neutrophil degranulation (Akgun et al. 2020). Cardozo et al. developed a high-throughput targeted proteomics assay to detect COVID-19 nucleoprotein peptides from nasopharyngeal and oropharyngeal swab samples. Data-dependent acquisition (DDA) analyses revealed around 119 unique peptides belonging to the eight SARS-CoV-2 proteins, out of which nucleoprotein (NCAP_WCPV) accounted for 23.5% of the identified peptides (Cardozo et al. 2020). Rivera et al. detected an average of 1,100 host proteins from the infected swab sample. The most abundant proteins detected in positive swabs were guanylate-binding protein 1, tapasin, and HLA class II histo-compatibility antigen DR beta chain. The biological processes altered in infected host cells were SRP-dependent cotranslational protein targeting membrane, viral transcription and translational initiation and nuclear-transcribed mRNA catabolic process, and nonsense-mediated decay (Rivera et al. 2020). Gouveia et al., with a 20-minute MS acquisition window, were able to identify and quantify several virus-specific peptides. They pointed out that the peptides ADETQALPQR (and its variant forms) and GFYAQGSR from the nucleocapsid protein are of most interest for developing rapid, targeted assays (Gouveia et al. 2020). Bankar et al. identified a few of the host proteins such as interleukin-6, ferritin, l-lactate dehydrogenase, C-reactive protein, and aspartate aminotransferase to be upregulated only in COVID-19-positive patients using targeted proteomics assay. The enriched pathways identified in the host were neutrophil degranulation, interleukin-12 (IL-12) signaling pathways, and mRNA translation of proteins (Bankar et al. 2021). Thus, the following studies indicate that MS-detected host proteins have a potential for monitoring the disease progression and the panel of these proteins can be used for clinical translation.
Inhibitory effect of particulate matter on toll-like receptor 9 stimulated dendritic cells by downregulating mitogen-activated protein kinase and NF-κB pathway
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Madeeha Arooj, Irshad Ali, Hee Kyoung Kang, Jin Won Hyun, Young-Sang Koh
Antigen-presenting cells secrete an important pro-inflammatory cytokine interleukin 12 (IL-12), also categorized as a T-cell stimulating factor, which orchestrates differentiation of naïve T-cells into CD4 T helper 1 (Th1) cells (Samperio 2010). Interleukin 6 (IL-6) is a multifunctional cell-signaling cytokine, known as anti- and pro-inflammatory cytokine initially recognized to be a stimulatory factor for B-cells (Scheller et al. 2011). Tumor necrosis factor-alpha (TNF-α) is involved in local and systemic infection. Liu et al. (2017) reported the inhibitory effect of TNF-α on viral replication and tumorigenesis. Following exposure to bacterial or viral infections, NF-κB and TNF-α regulate antimicrobial mediators (Abdul Cader et al. 2016).