Biomarkers of systemic treatment response in people with psoriasis: a scoping review.

Background: Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare.

Objectives: To perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community.

Biomarkers of disease progression in people with psoriasis: a scoping review.

Background: Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.

Objectives: To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.

Use of a baseline risk score to identify the risk of serious infectious events in patients with rheumatoid arthritis during certolizumab pegol treatment.

Background: The risk of serious infectious events (SIEs) is increased in patients with rheumatoid arthritis (RA). The aim of this study was to develop an age-adjusted comorbidity index (AACI) to predict, using baseline characteristics, the SIE risk in patients with RA treated with certolizumab pegol (CZP).

Methods: Data of CZP-treated patients with RA were pooled from the RAPID1/RAPID2 randomized controlled trials (RCT CZP) and their open-label extensions (All CZP).

A somatization comorbidity phenotype impacts response to therapy in rheumatoid arthritis: post-hoc results from the certolizumab pegol phase 4 PREDICT trial.

Background: Comorbidities may contribute to disease activity and treatment response in rheumatoid arthritis (RA) patients. We defined a somatization comorbidity phenotype (SCP) and examined its influence on response to certolizumab pegol (CZP) using data from the PREDICT trial.

Methods: Patients in PREDICT were randomized to the patient-reported Routine Assessment of Patient Index Data 3 (RAPID3) or physician-based Clinical Disease Activity Index (CDAI) for treatment response assessment.

The interplay between the lysine demethylase KDM1A and DNA methyltransferases in cancer cells is cell cycle dependent.

DNA methylation and histone modifications are key epigenetic regulators of gene expression, and tight connections are known between the two. DNA methyltransferases are upregulated in several tumors and aberrant DNA methylation profiles are a cancer hallmark. On the other hand, histone demethylases are upregulated in cancer cells.

DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients.

In addition to genetic predisposition, environmental and lifestyle factors contribute to the pathogenesis of type 2 diabetes (T2D). Epigenetic changes may provide the link for translating environmental exposures into pathological mechanisms. In this study, we performed the first comprehensive DNA methylation profiling in pancreatic islets from T2D and non-diabetic donors.

Regulation of mammalian DNA methyltransferases: a route to new mechanisms.

DNA methyltransferases (DNMTs) establish and maintain DNA methylation patterns at specific regions of the genome, thereby contributing to gene regulation. It is becoming evident that an intricate web of pathways target DNMTs to these genomic regions. Here, we review the understanding of these regulatory mechanisms and provide an overview of the new findings, emphasizing the emerging scenario in which several levels of regulation are coordinated to control DNMTs.

Exposing the DNA methylome iceberg.

DNA methylation was the first epigenetic modification discovered. Until recently, comprehensive coverage of the composition and distribution of methylated cytosines across the genome was lacking. Technological advances, however, are providing methylation maps that can reveal the genomic distribution of DNA methylation in different cell states or phenotypes.

Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders.

Numerous clinical, physiopathological and epidemiological studies have underlined the detrimental or beneficial role of nutritional factors in complex inflammation related disorders such as allergy, asthma, obesity, type 2 diabetes, cardiovascular disease, rheumatoid arthritis and cancer. Today, nutritional research has shifted from alleviating nutrient deficiencies to chronic disease prevention. It is known that lifestyle, environmental conditions and nutritional compounds influence gene expression.

Hyperactivated NF-{kappa}B and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells.

Interleukin-6 (IL-6), involved in cancer-related inflammation, acts as an autocrine and paracrine growth factor, which promotes angiogenesis, metastasis, and subversion of immunity, and changes the response to hormones and to chemotherapeutics. We explored transcription mechanisms involved in differential IL-6 gene expression in breast cancer cells with different metastatic properties. In weakly metastatic MCF7 cells, histone H3 K9 methylation, HP1 binding, and weak recruitment of AP-1 Fra-1/c-Jun, NF-kappaB p65 transcription factors, and coactivators is indicative of low chromatin accessibility and gene transcription at the IL-6 gene promoter.

Keeping up NF-kappaB appearances: epigenetic control of immunity or inflammation-triggered epigenetics.

Controlled expression of cytokine genes is an essential component of an immune response and is crucial for homeostasis. In order to generate an appropriate response to an infectious condition, the type of cytokine, as well as the cell type, dose range and the kinetics of its expression are of critical importance. The nuclear factor-kappaB (NF-kappaB) family of transcription factors has a crucial role in rapid responses to stress and pathogens (innate immunity), as well as in development and differentiation of immune cells (acquired immunity).

Attenuation of mitogen- and stress-activated protein kinase-1-driven nuclear factor-kappaB gene expression by soy isoflavones does not require estrogenic activity.

We have analyzed in molecular detail how soy isoflavones (genistein, daidzein, and biochanin A) suppress nuclear factor-kappaB (NF-kappaB)-driven interleukin-6 (IL6) expression. In addition to its physiologic immune function as an acute stress cytokine, sustained elevated expression levels of IL6 promote chronic inflammatory disorders, aging frailty, and tumorigenesis. Our results in estrogen-unresponsive fibroblasts, mitogen- and stress-activated protein kinase (MSK) knockout cells, and estrogen receptor (ER)-deficient breast tumor cells show that phytoestrogenic isoflavones can selectively block nuclear NF-kappaB transactivation of specific target genes (in particular IL6), independently of their estrogenic activity.

Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production.

Apoptotic cells are cleared by phagocytosis during development, homeostasis, and pathology. However, it is still unclear how necrotic cells are removed. We compared the phagocytic uptake by macrophages of variants of L929sA murine fibrosarcoma cells induced to die by tumor necrosis factor-induced necrosis or by Fas-mediated apoptosis.