PPAR Alpha as a Metabolic Modulator of the Liver: Role in the Pathogenesis of Nonalcoholic Steatohepatitis (NASH)

The strong relationship between metabolic alterations and non-alcoholic steatohepatitis (NASH) suggests a pathogenic interplay. However, many aspects have not yet been fully clarified. Nowadays, NASH is becoming the main cause of liver-associated morbidity and mortality. Therefore, an effort to understand the mechanisms underlying the pathogenesis of NASH is critical. Among the nuclear receptor transcription factors, peroxisome-proliferator-activated receptor alpha (PPARα) is highly expressed in the liver, where it works as a pivotal transcriptional regulator of the intermediary metabolism. In this context, PPARα's function in regulating the lipid metabolism is essential for proper liver functioning. Here, we review metabolic liver genes under the control of PPARα and discuss how this aspect can impact the inflammatory condition and pathogenesis of NASH

Multidisciplinary Management of Spondyloarthritis-Related Immune-Mediated Inflammatory Disease

Immune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis and uveitis

Patient-reported impact of spondyloarthritis on work disability and working life: The ATLANTIS survey

44noopenopenRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study groupRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study, Grou

Morphologic, dynamic and high-resolution microscopy MRI in early-onset spondyloarthritis finger dactylitis

Objective Up to now, the pathophysiology of SpA dactylitis has not been entirely clarified. It is not clear which are the involved tissues and which is the primary lesion of the "sausage-like" digit. The aim of our study was to examine the finger structures in early-onset finger dactylitis using high-resolution microscopy MRI together with morphologic and dynamic MRI. Subjects and methods In a 6-month period, 13 SpA patients (7 females and 6 males), mean age 54.07 years (range 37-73 years) and mean disease duration 7.07 years (range 1-44 years) with early-onset finger dactylitis (less than 3 months) were recruited. Nine patients had PsA, 3 HLA-B27-positive uSpA and 1 HLA-B27-negative uSpA. One patient had 2 dactylitis fingers. Ten healthy volunteers matched for age and sex with no personal and family history of SpA were enrolled. All dactylitis fingers and randomly selected fingers of the normal control subjects were imaged by morphologic, dynamic and high-resolution microscopy MRI. Results We have found flexor tenosynovitis in all the 14 dactylitis fingers, joint synovitis in 5 and oedema in the finger soft tissue in 10. In 2 dactylitis fingers, there was oedema at the insertion of the joint capsule suggesting enthesitis. In 5 dactylitis fingers, there was only mild enhancement at the enthesis organ (collateral ligament, flexor and extensor tendons). Conclusions Our MRI study on early-onset dactylitis demonstrates that flexor tenosynovitis, joint synovitis and oedema of the digit soft tissue are the predominant alterations visible in the early phase of evolution of dactylitis and that, therefore, enthesitis may not be considered the primary lesion of dactylitis

Follicular bisection in hair restoration: in vivo experiment.

[No abstract available

ACLY as a modulator of liver cell functions and its role in Metabolic Dysfunction-Associated Steatohepatitis

Abstract Background Non-alcoholic Fatty Liver Disease (NAFLD), now better known as Metabolic (Dysfunction)-Associated Fatty Liver Disease (MAFLD) and its progression to Nonalcoholic Steatohepatitis (NASH), more recently referred to as Metabolic (Dysfunction)-Associated Steatohepatitis (MASH) are the most common causes of liver failure and chronic liver damage. The new names emphasize the metabolic involvement both in relation to liver function and pathological features with extrahepatic manifestations. This study aims to explore the role of the immunometabolic enzyme ATP citrate lyase (ACLY), with a critical function in lipogenesis, carbohydrate metabolism, gene expression and inflammation. Methods ACLY function was investigated in TNFα-triggered human hepatocytes and in PBMC-derived macrophages from MASH patients. Evaluation of expression levels was carried out by western blotting and/or RT-qPCR. In the presence or absence of ACLY inhibitors, ROS, lipid peroxidation and GSSG oxidative stress biomarkers were quantified. Chromatin immunoprecipitation (ChIP), transient transfections, immunocytochemistry, histone acetylation quantitation were used to investigate ACLY function in gene expression reprogramming. IL-6 and IL-1β were quantified by Lumit immunoassays. Results Mechanistically, ACLY inhibition reverted lipid accumulation and oxidative damage while reduced secretion of inflammatory cytokines in TNFα-triggered human hepatocytes. These effects impacted not only on lipid metabolism but also on other crucial features of liver function such as redox status and production of inflammatory mediators. Moreover, ACLY mRNA levels together with those of malic enzyme 1 (ME1) increased in human PBMC-derived macrophages from MASH patients when compared to age-matched healthy controls. Remarkably, a combination of hydroxycitrate (HCA), the natural ACLY inhibitor, with red wine powder (RWP) significantly lowered ACLY and ME1 mRNA amount as well as IL-6 and IL-1β production in macrophages from subjects with MASH. Conclusion Collectively, our findings for the first time highlight a broad spectrum of ACLY functions in liver as well as in the pathogenesis of MASH and its diagnostic and therapeutic potential value. Graphical Abstrac