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Unlocking the NF-?B Conundrum: Embracing Complexity to Achieve Specificity.

ABSTRACT: Transcription factors of the nuclear factor ?B (NF-?B) family are central coordinating regulators of the host defence responses to stress, injury and infection. Aberrant NF-?B activation also contributes to the pathogenesis of some of the most common current threats to global human health, including chronic inflammatory diseases, autoimmune disorders, diabetes, vascular diseases and the majority of cancers. Accordingly, the NF-?B pathway is widely considered an attractive therapeutic target in a broad range of malignant and non-malignant diseases. Yet, despite the aggressive efforts by the pharmaceutical industry to develop a specific NF-?B inhibitor, none has been clinically approved, due to the dose-limiting toxicities associated with the global suppression of NF-?B. In this review, we summarise the main strategies historically adopted to therapeutically target the NF-?B pathway with an emphasis on oncology, and some of the emerging strategies and newer agents being developed to pharmacologically inhibit this pathway.

SUBMITTER: Begalli F

PROVIDER: S-EPMC5618308 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity.

Begalli Federica F Bennett Jason J Capece Daria D Verzella Daniela D D'Andrea Daniel D Tornatore Laura L Franzoso Guido G

Biomedicines 20170822 3

Transcription factors of the nuclear factor κB (NF-κB) family are central coordinating regulators of the host defence responses to stress, injury and infection. Aberrant NF-κB activation also contributes to the pathogenesis of some of the most common current threats to global human health, including chronic inflammatory diseases, autoimmune disorders, diabetes, vascular diseases and the majority of cancers. Accordingly, the NF-κB pathway is widely considered an attractive therapeutic target in a ...[more]

PMID: 28829404

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Project description:BackgroundHandwashing with soap is a cost-effective, efficient health behavior to prevent various diseases. Despite its immense health benefits, the lowest prevalence of handwashing is found in low-income countries. Here, its practice is not only determined by individual behavior, but also heavily shaped by deprivations in the social and structural ecology. Moreover, handwashing barriers are not equally experienced as overlapping social identities (e.g., age and gender) intersect and create inequities between members of different social groups. To embrace the complexities of handwashing beyond individual-level behavior and singular social identities, a combined socioecological and intersectional perspective is employed. This multi-level approach with regards to intersecting privileges and disadvantages serves as a basis to promote this highly important health behavior.MethodsThis study used a qualitative, theory-based approach and combined data from two samples: experts in health promotion (n = 22) and local citizens stratified by gender and rural/urban location (n = 56). Data was collected in face-to-face interviews in Sierra Leone between November 2018 and January 2019 and analyzed using thematic analysis and typology of the qualitative data.ResultsThe conceptualization of multi-level determinants of handwashing within a socioecological model showed the high relevance of inhibiting social and structural factors for handwashing practice. By establishing seven distinguishing social identity dimensions, data demonstrates that individuals within the same social setting yet with distinct social identities experience strikingly differing degrees of power and privileges to enact handwashing. While a local leader is influential and may also change structural-level determinants, a young, rural wife experiences multiple social and structural constraints to perform handwashing with soap, even if she has high handwashing intentions.ConclusionThis study provides a holistic analytical framework for the identification of determinants on multiple levels and accumulating intersections of socially produced inequalities for handwashing and is applicable to other health topics. As the exploration of handwashing was approached from a solution-focused instead of a problem-focused perspective, the analysis can guide multi-level intervention approaches (e.g., using low-cost, participatory activities at the community level to make use of the available social capital).

Dataset Information

Unlocking the NF-?B Conundrum: Embracing Complexity to Achieve Specificity.

Publications

Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity.

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