The transport and exchange systems: respiratory and cardiovascular
Nick Draper, Helen Marshall in Exercise Physiology, 2014
Lymphocytes, the most common agranulocyte are found within the blood but, more commonly, within the tissues of the lymphatic (immune) system. Nevertheless, they are the second most common leukocyte (25% of total) in the blood where their role involves producing immunoglobulins (antibodies) which are used to identify and neutralise bacteria and viruses. Monocytes, the largest type of leukocyte (around 6% of total leukocytes), are carried in the blood to sites of infection where they leave the blood to enter the infected tissue where they phagocytise pathogens. Monocytes play additional roles in antigen presentation (capturing antigens and presenting them to lymphocytes to activate an immune response against the antigen) and cytokine release. Cytokines are signal-ling molecules with a wide variety of immunomodulatory functions.
Gramicidin inhibits cholangiocarcinoma cell growth by suppressing EGR4
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Xiaoli Gong, Liming Zou, Miaomiao Wang, Yingheng Zhang, Shuxian Peng, Mingtian Zhong, Jiankui Zhou, Xun Li, Xiaodong Ma
To identify the potential therapeutic targets in cholangiocarcinoma cells treated with gramicidin, we performed RNA-sequencing (RNA-seq) using total RNA isolated from RBE cells treated with PBS or gramicidin for 12 h. After quality filtering and normalising the raw sequencing data, we identified differentially expressed genes (DEGs) based on the following criteria: fold change >2 or <0.5, p-value <.05. By comparing the reads per kilobase per million (RPKM) values between PBS and gramicidin treatment, a total of 265 DEGs (64 upregulated and 201 downregulated) were identified in RBE cells treated with gramicidin. Ingenuity Pathway Analysis (IPA) shown that most of enriched canonical pathway was involved the role of granulocyte adhesion, agranulocyte adhesion and IL-17A. Of note, several cholesterol biosynthesis pathways were enriched between PBS and gramicidin treatment, which indicated the possible key role of lipid metabolism pathway in cholangiocarcinoma cell growth (Figure 2(A,B)). Next, we found that early growth response protein 4 (EGR4) is one of the most down-regulated gene in identified DEGs (Figure 2(B)). Next, we performed quantitative real-time PCR (qPCR) to validate the RNA-seq data and found the mRNA of EGR4 was dramatically down-regulated in both RBE and HuCCT1 cholangiocarcinoma cells (Figure 2(C,D)). Accordingly, the protein level of EGR4 was significantly lower in RBE and HuCCT1 cells after gramicidin treatment (Figure 2(E,F)). These results implicate that gramicidin inhibits cholangiocarcinoma cell growth by downregulating EGR4 and EGR4 is a potential target in cholangiocarcinoma.
Pulmonary toxicity and gene expression changes in response to whole-body inhalation exposure to multi-walled carbon nanotubes in rats
Published in Inhalation Toxicology, 2022
Tina M. Sager, Christina M. Umbright, Gul Mehnaz Mustafa, Jenny R. Roberts, Marlene S. Orandle, Jared L. Cumpston, Walter G. McKinney, Theresa Boots, Michael L. Kashon, Pius Joseph
Bioinformatic analysis of the SDEGs identified the IPA biological functions and canonical pathways that were significantly enriched in the rat lungs in response to MWCNT-7 exposure. Lung cancer, leukocyte migration, inflammatory response, mitosis, cell movement of phagocytes, recruitment of leukocytes, inflammation of airway, accumulation of leukocytes, recruitment of phagocytes, and activation of macrophages were among the top ranking, enriched IPA biological functions (Figure 8(A)). The IPA canonical pathways that were significantly enriched and ranked high were kinetochore metaphase signaling pathway, granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, acute phase response signaling, LXR/RXR activation, complement system, TREM1 signaling, phagosome formation, cell cycle control of chromosomal replication, and communication between innate and adaptive immune cells (Figure 8(B)).
Lung toxicity and gene expression changes in response to whole-body inhalation exposure to cellulose nanocrystal in rats
Published in Inhalation Toxicology, 2021
Pius Joseph, Christina M. Umbright, Jenny R. Roberts, Jared L. Cumpston, Marlene S. Orandle, Walter G. McKinney, Tina M. Sager
Bioinformatic analysis of the SDEGs detected in the CNC exposed rat lungs identified significant enrichment in multiple IPA diseases and biological function categories. The top 10 most significantly enriched IPA diseases and biological function categories were transport of molecules, quantity of cells, inflammation of organ, rheumatic disease, inflammation of absolute anatomical region, cell movement of blood cells, leukocyte migration, inflammatory response, cell movement of leukocytes, and recruitment of granulocytes (Figure 9). Many other IPA biological functions related to cancer, oxidative stress, and fibrosis were also significantly enriched in response to CNC exposure (Supplemental Table 2). The top 10 most significantly enriched IPA canonical pathways were acute phase response signaling, granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, LXR/RXR activation, FXR/RXR activation, altered T cell and B cell signaling in rheumatoid arthritis, communication between innate and adaptive immune cells, phagosome formation, complement system, and role of IL-17A in psoriasis (Figure 10). Other significantly enriched canonical pathways included GADD45 signaling, circadian rhythm signaling, role of pattern recognition receptors in recognition of bacteria and viruses, production of nitric oxide and ROS in macrophages, NRF2-mediated oxidative stress response, toll-like receptor signaling, NFκB signaling, PPAR signaling, IGF-1 signaling, HIF1α signaling, calcium signaling, mTOR signaling and many cancer-related pathways (Supplemental Table 3). Gene Ontology (GO) enrichment analysis of the SDEGs confirmed the significant enrichment in many of the functions and pathways detected by the IPA analysis (data not presented).
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