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Biologic Therapies for Rheumatoid Arthritis
Published in Thomas F. Kresina, Monoclonal Antibodies, Cytokines, and Arthritis, 2020
Ian R. Mackay, Merrill J. Rowley, Claude C. A. Bernard
There is release of cytokines, particularly interleukin-1 (IL-1), after uptake of antigen by macrophages. II-1 and the related cytokine tumor necrosis factor (TNF) aid the immune response by activating T cells but also cause various local and sytemic adverse effects of rheumatoid inflammation. Interference with the secretion of IL-1 by antibody blockade or by other cytokines would obviously damp the afferent limb of the autoimmune response. However, it is more convenient to consider biotherapy based on cytokines in Sec. IV.D dealing with the efferent (effector) limb.
Serratia
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Naheed S. Kanji, Umesh Narsinghani, Ritu A. Kumar
Infections by Serratia and related microbes secrete a pore-forming toxin hemolysin/cytolysin, which is responsible for its virulence. This hemolysin ShIA is cytotoxic that lyses erythrocytes, leukocytes, and macrophages precipitating a systemic inflammatory response. The S. marcescens hemolysin represents the prototype of a growing family of pore-forming toxins. This cytotoxin is believed to aid in tissue penetration and may be linked to a widespread host invasive pathogenic pathway involving bacterial swarming, quorum sensing, and biofilm production. The hemolysin is determined by two genes, ShlA and shlB, arranged in tandem. ShlA encodes the hemolysin, and ShlB encodes the outer membrane protein that secretes ShlA. Both have proteins with signal sequences for export across the cytoplasmic membrane by the Sec system. ShlB not only secretes ShlA but also activates ShlA. The hemolysin was the first characterized example of a large group of proteins secreted by the two partner secretion system (TPSS) or type V-secretion system.62,63
The rab Gene Family
Published in Juan Carlos Lacal, Frank McCormick, The ras Superfamily of GTPases, 2017
Armand Tavitian, Ahmed Zahraoui
There is strong genetic evidence that SEC4 and YPT1: two small GTP-binding proteins highly related to mammalian rab proteins, are required for intracellular transport in S. cerevisiae. Thermosensitive mutations of the SEC4 gene impair the fusion of post-Golgi vesicles with the PM, suggesting that its product is required for the targeting and/or the fusion of vesicles with PM. In agreement with this, the SEC4p (p for protein) is found associated with the cytoplasmic face of vesicles in transit to the cell surface and the inner face of the PM.46 Further genetic studies have identified at least 10 genes to be essential for post-Golgi secretory events. One of these, SEC 15 localized on secretory vesicles, may be a SEC4 target. This suggests that SEC4 controls the formation of a complex between a docking protein, SEC15, and a PM target.47
Comprehensive bioinformatics analysis reveals the hub genes and pathways associated with multiple myeloma
Published in Hematology, 2022
Shengli Zhao, Xiaoyi Mo, Zhenxing Wen, Lijuan Ren, Zhipeng Chen, Wei Lin, Qi Wang, Shaoxiong Min, Bailing Chen
SEC61A1 encodes the α-subunit of the heteropolymeric SEC61 complex, which is essential in the process of secretion and insertion of polypeptides into the ER [32]. Abnormalities in SEC61A1 have been linked to the progression of kidney disease and liver cancer in humans [33–35]. In a B cell inactivation study, a decrease in the expression of SEC61A1 and the production of IgM and IgG were simultaneously observed, suggesting that the variation in SEC61 may be related to plasma cell deficiency [36]. Further research by Schubert et al. confirmed that B cells of SEC61A1 mutation carriers have an intrinsic deficiency to develop into plasma cells. At the same time, less immunoglobulin secretion was observed in EBV-transformed B cell lines carrying SEC61A1 mutations [37]. In our study, 7 protein-related pathways were enriched in the pathway interrelation analysis of SEC61A1, which indicated that the important regulatory role of SEC61A1 participates in protein metabolism (Figure 6B). Therefore, further studies are necessary and urgent to clarify the roles of SEC61A1 in the pathogenic mechanism of MM.
Cancer Chemopreventive Properties of Sulfated Enterolobium cyclocarpum Extract
Published in Nutrition and Cancer, 2021
Amira M. Gamal-Eldeen, Hassan Amer, Amani A Alrehaili, Ahmed Saleh, Abd El-Rahman Al Ghamdi, Nahed M Hawsawi, Asma Salman, Bassem M. Raafat
This study is a novel attempt that successfully prepared the sulfated water extract of EC. Taken together, this study indicated that SEC acts as an effective chemopreventive agent via both blocking and suppressing mechanisms. It showed effective tumor anti-initiating activity through CYP1A inhibition and GSTs induction; additionally, it has a potential anti-promoting property, as indicated by its anti-inflammatory activity, enhancing macrophage proliferation, increasing the binding affinity of FITC-LPS to macrophages and inhibiting the stimulated NO. SEC showed specific cytotoxicity against Hep G2 cells, but it induced the growth of lymphocytes. SEC led to a major disturbance in the cell cycle including arrest at both the S-and G2/M-phases in Hep G2 cells. This disturbance was associated with an induced-necrosis, but not apoptosis. In Vivo experiments indicated that SEC could reverse many DEN-induced histopathological changes and inhibit the tumor initiation stage.
cDNA expression library screening revealed novel functional genes involved in clear cell carcinogenesis of the ovary in vitro
Published in Journal of Obstetrics and Gynaecology, 2021
Yasushi Yamada, Tsutomu Miyamoto, Shotaro Higuchi, Motoki Ono, Hisanori Kobara, Ryoichi Asaka, Hirofumi Ando, Akihisa Suzuki, Tanri Shiozawa
SEC61B is one of the structural proteins of the transmembrane Sec61 complex, which is located on the endoplasmic reticulum and is involved in protein transport (Park and Rapoport 2012). Polypeptides newly synthesised in ribosomes are transferred to the endoplasmic reticulum through the Sec61 complex, folded, and become mature proteins. Unfolding proteins are carried to the cytoplasm through the Sec61 complex, and degenerated by the ubiquitin-proteasome pathway (Zimmermann et al. 2011). The overexpression of the Sec61B protein has been reported in colorectal cancer (Fan et al. 2011). In ovarian cancer cells, SEC61B has been shown to affect chemosensitivity via copper transport (Abada et al. 2012). Therefore, SEC61B may affect the chemosensitivity of CCC.