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The antibody-related immune response is mediated by immunoglobulins (Igs), soluble circulating glycoproteins produced by activated B cells that, upon the recognition of specific epitopes on pathogen surfaces, activate, proliferate, and differentiate into antibody-secreting plasma cells. Although the antibodies are effectors of the humoral immune adaptive response, their overproduction in response to a dysregulated proliferation of clonal plasma cell production in tumoral conditions (i.e., multiple myeloma), enriches the serum and urinary matrices, assuming the crucial role of biomarkers. Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the expansion and accumulation of clonally activated plasma cells in bone marrow, determining the release of high amounts of monoclonal component (MC) that can be detected as intact immunoglobulin (Ig), immunoglobulin fragments, or free light chains (FLCs). The importance of detecting biomarkers for the diagnosis, monitoring, and prognosis of diseases is highlighted by the international guidelines that recommend specific assays for the analysis of intact Igs and FLC. Moreover, a developed assay called Hevylite® allows for the quantification of immunoglobulins that are both involved (iHLC) and not involved (uHLC) in the tumor process; this is a fundamental aspect of following up the patient’s workup and evaluating the progression of disease, together with the treatments response. We here summarize the major points of the complex scenario involving monoclonal gammopathies and MM clinical management in view of advantages derived for the use of Hevylite®.

A radiological or nuclear attack could involve such a large number of subjects as to overwhelm the emergency facilities in charge. Resources should therefore be focused on those subjects needing immediate medical attention and care. In such a scenario, for the triage management by first responders, it is necessary to count on efficient biological dosimetry tools capable of early detection of the absorbed dose. At present the validated assays for measuring the absorbed dose are dicentric chromosomes and micronuclei counts, which require more than 2–3 days to obtain results. To overcome this limitation the NATO SPS Programme funded an Italian–Egyptian collaborative project aimed at validating a fast, accurate and feasible tool for assessing the absorbed dose early after radiation exposure. Biomarkers as complete blood cell counts, DNA breaks and radio-inducible proteins were investigated on blood samples collected before and 3 h after the first fraction of radiotherapy in patients treated in specific target areas with doses/fraction of about: 2, 3.5 or > 5 Gy and compared with the reference micronuclei count. Based on univariate and multivariate multiple linear regression correlation, our results identify five early biomarkers potentially useful for detecting the extent of the absorbed dose 3 h after the exposure.

Objective Mitochondria play pivotal roles in orchestrating signaling pathways in order to guarantee metabolic homeostasis under different stimuli. It has been demonstrated that the mito-nuclear communication is fundamental for facing physiological and/or stress-mediated cellular response through the activation of nuclear transcription factors. Here, we focused on the Forkhead box protein O1 (FoxO1) transcription factor that belongs to the FoxOs family proteins and is considered a “nutrients sensor” modulating the expression of nutrient-stress response genes. Methods In vitro and in vivo experimental systems, including 3T3-L1 white, X-9 beige and T37i brown adipocytes and different fat depots from C57BL/6 mice were used. The mitochondrial localization of FoxO1 was demonstrated by western blot analysis, confocal microscopy and chromatin immunoprecipitation assay, after sub-cellular compartment isolation. RT-qPCR analysis was used to evaluate the expression of antioxidant and mitochondrial genes after modulation of FoxO1 activity/localization. Treatment with diverse reactive oxygen species (ROS) species/sources were performed and assessed by cytofluorimetric analysis. Results We demonstrated that FoxO1 not exclusively localizes to cytosol and nucleus of adipocytes but also to mitochondria where it binds to mitochondrial DNA. We also proved that mitochondrial FoxO1 is phosphorylated upon normal feeding condition. Mitochondrial FoxO1 responds to starvation leaving mitochondrial compartment by ROS-mediated activation of the mitochondrial phosphatase PTPMT1. Indeed, FoxO1 de-phosphorylation and mito-to-nucleus shuttling was observed under starvation. Moreover, we provided evidence that ROS species/sources are able to differently modulate the mitochondrial localization of FoxO1. Conclusion The ability to localize at different cell compartments, including mitochondria, highlights a different layer of regulation of FoxO1 necessary for assuring a fast and efficient nutrient-stress response in white/beige adipose tissue. FoxO1 could be thus endorsed in the list of transcription factors involved in the mito-nuclear communication where ROS can act as upstream signals.

Scope Epigenetic aberrations caused by environmental factors and lifestyle choices have been associated with the development of a number of pathologies, including cardiovascular disorders. However, whether obesity-related heart dysfunction can occur via epigenetic mechanisms is largely undisclosed. The manifested role of DNA hydroxymethylation in heart pathophysiology prompts an investigation of its levels/machinery in heart of mice fed with high-fat diet (HFD) and its possible relation with genes linked to obesity-associated cardiac remodeling. Methods and results Alterations in levels of DNA methylation/hydroxymethylation modifications and in expression of Tet family of DNA hydroxylases are observed in hearts of mice treated with HFD for 8 and 16 weeks. Decreased levels of the Tet co-substrate α-ketoglutarate are also observed and associate with mitochondrial mass reduction and augmented oxidative stress. Finally, expression markers of cardiac remodeling are monitored by RT-qPCR analysis and associate with DNA hydroxymethylation signature by DNA immunoprecipitation and correlation analyses. Conclusion Global changes of DNA hydroxymethylation in hearts of HFD-fed mice are associated with upregulation of the dioxygenase Tet3 and decreased content of α-ketoglutarate. A relation between Tet genes and markers of cardiac hypertrophic response is observed and, if further validated, it will provide insights concerning epigenetics and obesity-related cardiac complications.