Circulating perilipin 2 levels are associated with fat mass, inflammatory and metabolic markers and are higher in women than men.

Perilipin 2 (PLIN2) is a protein involved in lipid storage and metabolism in non-adipose tissues. Detectable levels of circulating PLIN2 (cPLIN2) have been reported to be associated with some types of cancer, but no systematic analysis of age-related modifications in cPLIN2 levels has ever been performed. We measured serum cPLIN2 in a group of old people including centenarians in comparison with young subjects and tested possible correlations with parameters of body composition, fat and glucose metabolism, and inflammation. We found that: i. levels of cPLIN2 do not change with age, but women have higher levels of cPLIN2 with respect to men; ii. cPLIN2 levels strongly correlate to BMI, as well as fat and lean mass; iii. cPLIN2 levels strongly correlate with the proinflammatory adipokine leptin. Due to the adipogenic activity of leptin, it is hypothesized that cPLIN2 is affected and possibly regulated by this pleiotropic adipokine. Moreover, these results suggest that cPLIN2 (possibly together with leptin) could be assumed as a proxy for body adiposity.

Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting.

The Sarcolab pilot study of 2 crewmembers, investigated before and after a 6-mo International Space Station mission, has demonstrated the substantial muscle wasting and weakness, along with disruption of muscle's oxidative metabolism. The present work aimed at evaluating the pro/anti-inflammatory status in the same 2 crewmembers (A, B). Blood circulating (c-)microRNAs (miRs), c-proteasome, c-mitochondrial DNA, and cytokines were assessed by real-time quantitative PCR or ELISA tests. Time series analysis was performed ( i.e., before flight and after landing) at 1 and 15 d of recovery (R+1 and R+15, respectively). C-biomarkers were compared with an age-matched control population and with 2-dimensional proteomic analysis of the 2 crewmembers' muscle biopsies. Striking differences were observed between the 2 crewmembers at R+1, in terms of inflamma-miRs (c-miRs-21-5p, -126-3p, and -146a-5p), muscle specific (myo)-miR-206, c-proteasome, and IL-6/leptin, thus making the 2 astronauts dissimilar to each other. Final recovery levels of c-proteasome, c-inflamma-miRs, and c-myo-miR-206 were not reverted to the baseline values in crewmember A. In both crewmembers, myo-miR-206 changed significantly after recovery. Muscle biopsy of astronaut A showed an impressive 80% increase of α-1-antitrypsin, a target of miR-126-3p. These results point to a strong stress response induced by spaceflight involving muscle tissue and the proinflammatory setting, where inflamma-miRs and myo-miR-206 mediate the systemic recovery phase after landing.-Capri, M., Morsiani, C., Santoro, A., Moriggi, M., Conte, M., Martucci, M., Bellavista, E., Fabbri, C., Giampieri, E., Albracht, K., Flück, M., Ruoss, S., Brocca, L., Canepari, M., Longa, E., Di Giulio, I., Bottinelli, R., Cerretelli, P., Salvioli, S., Gelfi, C., Franceschi, C., Narici, M., Rittweger, J. Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting.

Inflammaging and cancer: a challenge for the Mediterranean diet.

Aging is considered the major risk factor for cancer, one of the most important mortality causes in the western world. Inflammaging, a state of chronic, low-level systemic inflammation, is a pervasive feature of human aging. Chronic inflammation increases cancer risk and affects all cancer stages, triggering the initial genetic mutation or epigenetic mechanism, promoting cancer initiation, progression and metastatic diffusion. Thus, inflammaging is a strong candidate to connect age and cancer. A corollary of this hypothesis is that interventions aiming to decrease inflammaging should protect against cancer, as well as most/all age-related diseases. Epidemiological data are concordant in suggesting that the Mediterranean Diet (MD) decreases the risk of a variety of cancers but the underpinning mechanism(s) is (are) still unclear. Here we review data indicating that the MD (as a whole diet or single bioactive nutrients typical of the MD) modulates multiple interconnected processes involved in carcinogenesis and inflammatory response such as free radical production, NF-κB activation and expression of inflammatory mediators, and the eicosanoids pathway. Particular attention is devoted to the capability of MD to affect the balance between pro- and anti-inflammaging as well as to emerging topics such as maintenance of gut microbiota (GM) homeostasis and epigenetic modulation of oncogenesis through specific microRNAs.

Immunoproteasome in cancer and neuropathologies: a new therapeutic target?

Immunoproteasome is an emerging biological target that constitutes a key element not only in antigen presentation but also in T cell and cytokine regulation as well as cellular homeostasis. Respect to standard proteasome, the inducible expression and different sensitivity towards activity modulators of immunoproteasome render it a potential therapeutic target for tumours and central nervous system diseases. In this review we report the cutting edge studies for understanding when immunoproteasome expression is induced and how it regulates pivotal pathways involved in tumours and neuropathologies, including apoptosis and inflammation. We emphasize its role as a new pharmacological target by describing the recent medicinal chemistry efforts aimed at design selective small-molecule modulators of both standard- and immuno-proteasome forms. Finally, we also present an in silico model of the human immunoproteasome structure by the major molecular differences with the 20S standard proteasome and discuss the perspective for the design of novel specific smallmolecule modulators for the different proteasome isoforms.

Immunoproteasome expression is induced in mesial temporal lobe epilepsy.

Immunoproteasome has been associated to neurodegenerative and autoimmune diseases as a marker and regulator of inflammatory mechanisms. Its expression in the brain may occur upon neuroinflammation in different cell types and affect a variety of homeostatic and inflammatory pathways including the oxidized protein clearance and the self-antigen presentation. In the present study we investigated the immunoproteasome expression in hippocampi and cortex of patients affected by different histopathological forms of pharmaco-resistent mesial temporal lobe epilepsy. We identified a pathology-specific pattern of immunoproteasome expression, which could provide insight into the complex neuroinflammatory pathogenic components of this disease.