Identification and physiological significance of temporal NFκB signaling codewords deployed by macrophages to classify immune threats

Acute and chronic inflammatory pathologies involve misregulation of macrophage functions. Physiologically, macrophages are immune sentinels that initiate inflammatory responses via the transcription factor NFκB. The temporal pattern of NFκB activity determines which genes are expressed, suggesting that a temporal signaling code specifies a stimulus-appropriate immune response. To identify the signaling codewords, we developed tools to enable high-throughput analysis of live, primary macrophages responding to host- and pathogen-derived stimuli. An information-theoretic workflow identified six dynamical features that constitute codewords that convey stimulus information to the nucleus. In particular, “oscillatory” trajectories are a hallmark of the responses to host cytokine TNF. Remarkably, examining macrophages derived from a systemic autoimmune disease model suggests that confusion of two NFκB signaling codewords, and thus miscoding of TNF as a pathogen-derived stimulus, may underlie sporadic inflammatory pathology. Overall, this study identifies six codewords of the temporal NFκB signaling code for classifying immune threats and demonstrates their biological significance.

NFkappaB is a Key Player in the Crosstalk between Inflammation and Cardiovascular Diseases

Inflammation is a key mechanism of cardiovascular diseases. It is an essential component of atherosclerosis and a significant risk factor for the development of cardiovascular events. In the crosstalk between inflammation and cardiovascular diseases, the transcription factor NFκB seems to be a key player since it is involved in the development and progression of both inflammation and cardiac and vascular damage. In this review, we deal with the recent findings of the role of inflammation in cardiac diseases, focusing, in particular, on NFκB as a functional link. We describe strategies for the therapeutic targeting of NFκB as a potential strategy for the failing heart.

Clinical and Pharmacological Basis for the Use of Drugs Inhibiting of the RAAS in Patients with Diabetic Neuropathy

Diabetes mellitus (DM) is the most common cause of diabetic neuropathy (DN) comprises a heterogeneous group of disorders that can cause neuronal dysfunction throughout the human body. The incidence of diabetes and its complications is increasing to staggering proportions. In 2014 the WHO estimated an overall prevalence of 422 million (8, 5%). The incidence of diabetic neuropathy approaches 50% in most diabetic populations; there is no treatment, and its consequences in the form of foot ulceration and amputation. The recent studies suggest that the renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure. In the same time the metabolic abnormalities associated with diabetes lead to activation RAAS, which might promote the formation of reactive oxygen species to lead the endothelial and neuronal dysfunctions. Furthermore, TNFα is part of the response of the organism to hypertension and is originally described as one of the central mediators of inflammation trough the activation of transcription factor NFκB an important factor in the control of cell proliferation, differentiation, and apoptosis. Methodology & Theoretical Orientation: The study is going on in parallel groups. The patients (enrolled on randomized principle) with DPN will be investigated. The enrolled subjects was divided into two main groups: group I with Type I and Type II DM, complicated by DPN to take Aliskiren and group II with the same pathology, proceeding with the treatment without Aliskiren but given Telmisartan, for certainty of Aliskiren efficacy. At the start of the trial and on completion of the six week period TNFα level and C-peptide will be determined. Findings: Telmisartan has less TNFα modulatory effects then Aliskiren, Namely, the symptoms of neuropathy a well as blood TNFα level and C-peptide level are not changed significantly. Conclusion & Significance: TNFα is involved in DPN pathogenesis formation and clinical manifestation. Aliskiren ameliorates symptoms in DPN patients by modulatory impact on TNFα, so we have results for clinical and pharmacological analysis of Aliskiren application in DPN. The involvements of RAAS system in developments of DNP needs further research study.