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Mite allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Enrique Fernández-Caldas, Leonardo Puerta, Luis Caraballo, Victor Iraola, Richard F. Lockey
Der f 24 was identified as an ubiquinol-cytochrome c reductase binding protein (UQCRB)–like protein homologue. D. farinae UQCRB-like protein clustered with proteins of other arthropods but branched away from the cluster, underscoring its uniqueness. Serum IgE reactivity was demonstrated in 22 sera from mite-allergic patients to the recombinant UQCRB by ELISA and positive SPT in five of ten subjects tested [132].
Mitochondrial DNA Mutations and Mitochondrial Diseases
Published in Sara C. Zapico, Mechanisms Linking Aging, Diseases and Biological Age Estimation, 2017
Although 72 of the 85 subunits that form the respiratory chain complexes are encoded in the nucleus, mutations in such genes are rare. This might be a reflection of the highly deleterious nature of these mutations, which would result in lethality during embryogenesis. To date, mutations have been described in subunits of complex I (NDUFS 1, 2, 3, 4, 7 and 8, NDUFV1 and 2, and NDUFA1 and 11), associated with Leigh syndrome, encephalomyopathy, leukodystrophy and the four subunits of complex II (SDHA, B, C and D) associated with Leigh syndrome and ataxia in the case of the A subunit, and more rarely paraganglioma and feocromocitoma in the case of subunits B, C, and D. Mutations have also been described in complex III subunits UQCRB and UQCRQ associated with hypoglycemia, lactic acidosis and severe psychomotor delay with extra pyramidal signs, as well as a mutation in the complex IV (COX6B1) associated with childhood encephalomyopathy (Zhu et al. 2009).
Mitochondrial-targeted penetrating peptide delivery for cancer therapy
Published in Expert Opinion on Drug Delivery, 2018
Jiao Wu, Jason Li, Hu Wang, Chang-Bai Liu
Ubiquinol-cytochrome c reductase binding protein (UQCRB), a component of the mitochondrial complex III, has been recently concerned in angiogenesis, and widely recognized in targeting mitochondria to balance vascular homeostasis. However, the effect of UQCRB replenishment by direct delivery remains unknown. To explore the biological function of UQCRB, Chang J [106] generated a novel PTD-conjugated UQCRB fusion protein. PTD-UQCRB localized to mitochondria as does endogenous UQCRB. Treatment with PTD-UQCRB generated mitochondrial ROSwithout cytotoxicity, following hypoxia inducible factor-1α (HIF-1α) stabilization and downstream vascular endothelial growth factor expression. Accordingly, PTD-UQCRB induced angiogenesis in vitro and PTD-UQCRB pro-angiogenic activity was further validated in Matrigel plug assay and in cutaneous wound-healing mouse models in vivo. Together, these results demonstrate that the developed cell-permeable PTD-UQCRB can be utilized as a pro-angiogenic agent, and CPP conjugated with mitochondrial-targeted molecules is advisable strategy for cancer therapy.
Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing
Published in OncoImmunology, 2022
Wen-Sa Peng, Xin Zhou, Wen-Bin Yan, Yu-Jiao Li, Cheng-Run Du, Xiao-Shen Wang, Chun-Ying Shen, Qi-Feng Wang, Hong-Mei Ying, Xue-Guan Lu, Ting-Ting Xu, Chao-Su Hu
A PPI network was constructed using the STRING database to reveal the interactions between the DEGs upregulated in rNPC. Using the MCODE in Cytoscape, three modules that might play important roles in the characteristics of rNPC were detected (Figure 5F). Module 1 correlated with antigen presentation, consisting of both MHC-I (HLA-A/B/C/E/F) and MHC-II (HLA-DQ/DP/DR) molecules. Upregulation of these genes in rNPC indicated decreased tumor immune escape and increased T cell recognition/activation, which further confirmed increased immunogenicity of rNPC cancer cells. Module 2 consisted of KRT genes encoding keratins, which are the typical intermediate filament proteins of the epithelium. KRT6/16/17 are constitutive keratins with a relatively high proliferative state and are induced upon stress, injury, or inflammation. KRT5 is commonly used to diagnose undifferentiated NPCs.43 This module showed an altered epithelial differentiation state in patients with the complicated epithelial cell development process. Module 3 consisted of enzymes responsible for ATP synthesis (ATP5L/ATP5F1/ATP5H/ATP5G3) and the mitochondrial respiratory chain (COX5B/COX7B/COX4I1 and UQCRB/UQCRQ), consistent with increased oxidative phosphorylation (OXPHOS) and hypoxia in rNPC. With high metastatic and tumorigenic potential, cancer stem cells are more reliant on OXPHOS than the bulk and putatively nonstem components.44 Thus, OXPHOS inhibitors could be used to target rNPC and alleviate therapeutically adverse tumor hypoxia. Apart from the hub genes listed, the heatmap of DEGs showed that some immune-related genes, such as chemokines (CXCL1, CXCL8, CXCL14, and CCL20) and inhibitors (IDO1), were highly expressed in rNPC, indicating a complex immune response of these cancer cells (Figure S4E).