Search results for "Inflammation."

Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach

2018

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This netw…

Noncoding RNAs in Critical Limb Ischemia

2020

Peripheral artery disease, caused by chronic arterial occlusion of the lower extremities, affects over 200 million people worldwide. Peripheral artery disease can progress into critical limb ischemia (CLI), its more severe manifestation, which is associated with higher risk of limb amputation and cardiovascular death. Aiming to improve tissue perfusion, therapeutic angiogenesis held promise to improve ischemic limbs using delivery of growth factors but has not successfully translated into benefits for patients. Moreover, accumulating studies suggest that impaired downstream signaling of these growth factors (or angiogenic resistance) may significantly contribute to CLI, particularly under h…

2020

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the Huntingtin gene. As disease-modifying therapies for HD are being developed, peripheral blood cells may be used to indicate disease progression and to monitor treatment response. In order to investigate whether gene expression changes can be found in the blood of individuals with HD that distinguish them from healthy controls, we performed transcriptome analysis by next-generation sequencing (RNA-seq). We detected a gene expression signature consistent with dysregulation of immune-related functions and inflammatory response in peripheral blood from HD ca…

Nuclear Factor Kappa B Signaling Complexes in Acute Inflammation.

2020

[Significance]: Nuclear factor kappa B (NF-κB) is a master regulator of the inflammatory response and represents a key regulatory node in the complex inflammatory signaling network. In addition, selective NF-κB transcriptional activity on specific target genes occurs through the control of redox-sensitive NF-κB interactions.

Heterogeneity of biomaterial-induced multinucleated giant cells: Possible importance for the regeneration process?

2015

Biomaterial-associated multinucleated giant cells (BMGCs) have been found within the implantation beds of many different biomaterials. However, their exact differentiation and their involvement in the inflammatory and healing events of the foreign body response still remain mostly unclear. Silk fibroin (SF) scaffolds, which induces a tissue reaction involving both macrophages and BMGCs, was implanted in the subcutaneous connective tissue of four CD-1 mice for 15 days using an established subcutaneous implantation model. Analysis of macrophage polarization and BMGCs was performed by immunohistochemcial detection of pro- (cyclooxygenase-2 (COX-2), C-C chemokine receptor type 7 (CCR7), nuclear…

The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19

2021

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 over…

Context- and Tissue-Specific Regulation of Immunity and Tolerance by Regulatory T Cells

2016

The immune system has evolved to defend the organism against an almost infinite number of pathogens in a locally confined and antigen-specific manner while at the same time preserving tolerance to harmless antigens and self. Regulatory T (Treg) cells essentially contribute to an immunoregulatory network preventing excessive immune responses and immunopathology. There is emerging evidence that Treg cells not only operate in secondary lymphoid tissue but also regulate immune responses directly at the site of inflammation. Hence, the classification of Treg cells might need to be further extended by Treg cell subsets that are functionally and phenotypically polarized by their residency. In this…

Reply to Comment on Huang, X., et al. “Sourdough Fermentation Degrades Wheat Alpha-Amylase/Trypsin Inhibitor (ATI) and Reduces Pro-Inflammatory Activ…

2020

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N-retinylidene-N-retinylethanolamine adduct induces expression of chronic inflammation cytokines in retinal pigment epithelium cells

2021

Blindness due to photoreceptor degeneration is observed in both genetic and acquired eye disorders. Long blue light exposure can contribute to increase levels of oxidative compounds within the retinal pigment epithelium (RPE), enhancing risk of retinal damage. In retina, reactive oxygen species contribute to the activation of inflammatory cascade. If chronic, this inflammatory response can result in photoreceptor death. Therefore, we investigated the effects of the endogenous adduct N-retinylidene-N-retinylethanolamine (A2E) on RPE cells, in order to identify the most dysregulated cytokines and their related inflammatory pathways. RPE cells were exposed to A2E and blue light for 3h and 6h. …

Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and …

2020

The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELIS…