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Medicinal Plants for Eczema
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Plant-based compounds that are used to modulate NF-κB activity include kamebakaurin, acanthoic acid, isohelenin and parthenolide. Both kamebakaurin, isolated from Isodon japonicus (Burm. f.) H. Hara, and acanthoci acid, derived from Acanthopanax koreanum Nakai, have been shown to interfere with the NF-κB activation cascade. Isohelenin, isolated from Arnica montana L., prevents IκB degradation by alkylating the p69 subunit of NF-κB, and parthenolide, derived from Tanacetum parthenium (L.) Sch. Bip., binds to and inhibits I kappa B kinase beta (IKK-β) (Palladino et al., 2003).
Intracellular Maturation of Acute Phase Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Erik Fries, E. Mathilda Sjöberg
Studies during the last 10 years have revealed that all cells possess a system for stopping incompletely folded or otherwise defective secretory proteins from leaving the cell (reviewed in Reference 22). The key component in this system is a soluble ER protein called the immunoglobulin heavy-chain binding protein, or BiP. This protein was discovered when it was observed to coprecipitate with the heavy chain of IgG in cells producing only this subunit.29 Later, BiP was found to bind to other incomplete or aberrant proteins.30 BiP apparently binds to polypeptide structures which are normally hidden.31 Proteins that fail to leave the ER, such as the PiZ α1-antitrypsin variant, are eventually degraded in a nonly-sosomal compartment through a process that is poorly understood.32,33
Analysis of Vaccine Studies and Causal Inference
Published in Leonhard Held, Niel Hens, Philip O’Neill, Jacco Wallinga, Handbook of Infectious Disease Data Analysis, 2019
The problem is that in people in the control group for whom , the value of , the surrogate value under vaccination, is not observed. That is, is a missing potential outcome under . To assess whether an immunological measurement is a specific principal surrogate of protection, knowledge about is needed. That is, we need to be able to predict the immune response that an unvaccinated participant would have had if vaccinated. Follmann (2006) proposed two augmented vaccine trial designs to address the missing potential outcomes. The first approach, called “baseline immunogenicity predictor” (BIP), needs some variable measured pre-vaccination that predicts the immune response to vaccination. The BIP strategy develops an imputation model for the unobserved baseline immune measure based on the observed relationship between baseline covariates and biomarker values. Follmann (2006) suggested to vaccinate with another vaccine. But that can be hard to implement, and the immune response to two different antigens, the vaccine of interest and the irrelevant vaccine, could be quite different. One option for a good BIP is measurement of the same marker used as the candidate surrogate at baseline.
Identification and validation of core genes in tumor-educated platelets for human gastrointestinal tumor diagnosis using network-based transcriptomic analysis
Published in Platelets, 2023
Yuhong Jiang, Jun He, Xiaobo Wang, Chao Liu, Weihan Zhou, Dekun Liu, Zhushu Guo, Kuijie Liu
Next, the association between the proteins encoded by these TEP DEGs was investigated using PPI network analysis. We find that among the TEP DEGs of the core subnetwork, CDK1 and HSPA5 have the highest degree values. Thereby, this two-gene diagnostic signature may be used for GI cancer detection. Cyclin-dependent kinase (CDK1), also known as cell division control protein 2 (CDC2), is essential for directing the cell cycle in all cell types.47 Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5), also named Glucose-Regulated Protein 78 (GRP78) or immunoglobulin heavy chain binding protein (BiP), is a chaperone heat shock protein that expresses in all eukaryotes on the membrane of Endoplasmic Reticulum (ER).48 GRP78 is overexpressed on the membranes of many cancer cells, which makes GI malignancies like PAAD and CRC more aggressive.49 Although according to previous studies,50 HSPA5 is aberrantly activated in tumor tissues compared to normal control, however, its expression changes in TEPs seems to be the opposite as revealed by our study. Therefore, here we discover a novel two-gene signature specifically in platelets for GI tumor diagnosis.
M2 macrophage-derived exosomes suppress tumor intrinsic immunogenicity to confer immunotherapy resistance
Published in OncoImmunology, 2023
Naisheng Zheng, Tingting Wang, Qin Luo, Yi Liu, Junyao Yang, Yunlan Zhou, Guohua Xie, Yanhui Ma, Xiangliang Yuan, Lisong Shen
To understand the detailed molecular mechanism of how ApoE enrichment elicits lower MHC-I expression, we sought to identify the direct functional protein of ApoE in tumor cells through Co-IP followed by LC-MS. Among the multiple proteins that potentially interact with ApoE, binding immunoglobulin protein (BiP; also termed GRP78) is the top protein binding with ApoE with the highest affinity (Figure 5A, Table S6). BiP, a major endoplasmic reticulum (ER) chaperone, acts as the primary sensor in the activation of the unfolded protein response, reducing ER stress levels due to an enhancement of the cellular folding capacity. Importantly, proper folding and assembly in the ER are essential steps for the expression of functional MHC-I molecules on the cell surface,35 and BiP was reported to regulate the MHC-I repairing and loading.36 Thus, we focus on BiP protein to figure out the molecular mechanism of ApoE-mediated MHC-I loss. By immunoprecipitation assay, we validated that ApoE binds with BiP (Figure 5B). Confocal co-localization assay also validated that M2-exosomal ApoE also interacted and colocalized with BiP in M2-Exo-treated MC38 cells (Figure 5C, Figure S8G).
The endoplasmic reticulum chaperone BiP: a target for immunogenic cell death inducers?
Published in OncoImmunology, 2022
Oliver Kepp, Lucillia Bezu, Guido Kroemer
The unfolded protein response (UPR) is a type of ER stress that is activated in response to the accumulation of unfolded or misfolded proteins in the ER lumen. In this context, the ER chaperone heat shock protein family A member 5 (HSPA5, better known as binding immunoglobulin protein, BiP) acts as an ER stress sensor. Misfolded proteins present in the ER lumen interact with BiP, thus causing its dissociation from several effectors of the UPR: ER to nucleus signaling 1 (ERN, best known as IRE1α), eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3, best known as PERK) and activating transcription factor 6 (ATF6). This then triggers the alternative splicing of X-box binding protein 1 (XBP1) mRNA by IRE1α, the phosphorylation of eukaryotic initiation factor a (eIF2α) by PERK (with downstream expression of ATF4), and the nuclear translocation of ATF6. ATF4, ATF6 and the short form of XBP1 (XBP1s) act as transcription factors that, in combination with the phospho-eIF2α-mediated suppression of cap-dependent protein translation, activate a transcriptional and translational response altering the cellular proteome for homeostatic adaptation and cellular survival4,5 (Figure 1a). Of note, in the case of failure of the adaptive responses, the prolongation of ER stress in time results in the transactivation of DNA damage inducible transcript 3 (DDIT3, better known as C/EBP homologous protein, CHOP), thus leading to the induction of apoptotic cell death.6