👤 Massimo Federici

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality in individuals with diabetes, partly driven by dyslipidemia. While low-density lipoprotein cholesterol (LDL-C) reduction is the primary target of lipid management, many patients with diabetes exhibit mixed dyslipidemia characterised by elevated triglycerides and increased concentrations of atherogenic remnant lipoproteins, which are more comprehensively captured by non-high-density lipoprotein cholesterol (non-HDL-C). Current guidelines from international societies, including the American Diabetes Association (ADA), the American Association of Clinical Endocrinology (AACE), and the European Society of Cardiology (ESC), recommend LDL-C and non-HDL-C targets based on individual cardiovascular risk profiles. Despite clear therapeutic algorithms, lipid target attainment remains suboptimal in routine clinical practice, necessitating more intensive and individualised treatment strategies. Lipid-lowering therapies, including statins, ezetimibe, bempedoic acid and PCSK9 inhibitors, effectively reduce LDL-C and non-HDL-C, significantly lowering cardiovascular risk. Triglyceride-lowering therapies, including omega-3 fatty acids and fibrates, have demonstrated substantial reductions in triglyceride levels, but their impact on cardiovascular outcomes remains uncertain. Given the heterogeneity of dyslipidemia in diabetes, non-HDL-C and apolipoprotein B (apoB) have emerged as superior markers for assessing atherogenic burden. While LDL-C reduction remains central, additional efforts are needed to optimise the management of residual atherogenic lipoprotein particles in diabetes. Future research should focus on refining risk stratification, improving lipid target attainment, and integrating novel lipid-modifying agents to enhance cardiovascular outcomes in this high-risk population. Show less

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is fundamental to increasing survival and therapeutic adjustment. In stages II-IV especially, additional indications for adjuvant therapy purposes after resection and for treatment of metastatic patients are urgently needed. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) derived from the plasma of stage 0-I, II and III-IV melanoma patients ( Show less

Serum proteome investigations have raised an incredible interest in the research of novel molecular biomarker, nevertheless few of the proposed evidences have been translated to the clinical practice. One of the limiting factors has been the lack of generally accepted guidelines for clinical proteomics studies and the lack of a robust analytical and pre-analytical ground for the proposed classification models. Pre-analytical issues may results in a deep impact for biomarker discovery campaign. In this study we present a systematic evaluation of sample storage and sampling conditions for clinical proteomics investigations. We have developed and validated a linear MALDI-TOF-MS protein profiling method to explore the low protein molecular weight region (5-20 kDa) of serum samples. Data normalization and processing was performed using optimise peak detection routine (LIMPIC) able to describe each group under investigation. Data were acquired either from healthy volunteers and from multiple sclerosis patients in order to highlight ex vivo protein profile alteration related to different physio-pathological conditions. Our data showed critical conditions for serum protein profiles depending on storage times and temperatures: 23 degrees C, 4 degrees C, -20 degrees C and -80 degrees C. We demonstrated that upon a -20 degrees C short term storage, characteristic degradation profiles are associated with different clinical groups. Protein signals were further identified after preparative HPLC separation by peptide sequencing on a nanoLC-Q-TOF TANDEM mass spectrometer. Apolipoprotein A-IV and complement C3 protein fragments, transthyretin and the oxidized isoforms in different apolipoprotein species represent the major molecular features of such a degradation pattern. Show less

Leber's hereditary optic neuropathy (LHON) is a genetic disease leading to the loss of central vision and optic nerve atrophy. The existence of occasional cases of LHON patients developing a Multiple Sclerosis (MS)-like illness and the hypothesis that mtDNA variants may be involved in MS suggest the possibility of some common molecular mechanisms linking the two diseases. We have pursued a comparative proteomics approach on cerebrospinal fluid (CSF) samples from LHON and MS patients, as well as healthy donors by employing 2-DE gel separations coupled to MALDI-TOF-MS and nLC-MS/MS investigations. 7 protein spots showed significant differential distribution among the three groups. Both CSF of LHON or MS patients are characterized by lower level of transthyretin dimer adduct while a specific up regulation of Apo A-IV was detected in LHON CSF. Show less