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Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease worldwide. In 20%-30% of MASLD patients, the disease progresses to metabolic dysfunction-associated steatohepatitis (MASH, previously NASH) which can lead to fibrosis/cirrhosis, liver failure as well as hepatocellular carcinoma (HCC). Here we investigated the role of histidine-rich glycoprotein (HRG), a plasma protein produced by hepatocytes, in MASLD/MASH progression and HCC development. Methods: The role of HRG was investigated by morphological, cellular, and molecular biology approaches in (a) HRG knock-out mice (HRG-/- mice) fed on a CDAA dietary protocol or a MASH related diethyl-nitrosamine/CDAA protocol of hepatocarcinogenesis, (b) THP1 monocytic cells treated with purified HRG, and (c) well-characterized cohorts of MASLD patients with or without HCC. Results: In non-neoplastic settings, murine and clinical data indicate that HRG increases significantly in parallel with disease progression. In particular, in MASLD/MASH patients, higher levels of HRG plasma levels were detected in subjects with extensive fibrosis/cirrhosis. When submitted to the procarcinogenic protocol, HRG-/- mice showed a significant decrease in the volume and number of HCC nodules in relation to decreased infiltration of macrophages producing pro-inflammatory mediators, including IL-1b, IL-6, IL-12, IL-10, and VEGF as well as impaired angiogenesis. The histopathological analysis (H-score) of MASH-related HCC indicate that the higher HRG positivity in peritumoral tissue significantly correlates with a lower overall patient survival and an increased recurrence. Moreover, a significant increase in HRG plasma levels was detected in cirrhotic (F4) patients and in patients carrying HCC vs. F0/F1 patients. Conclusion: Murine and clinical data indicate that HRG plays a significant role in MASLD/MASH progression to HCC by supporting a specific population of tumorassociated macrophages with pro-inflammatory response and pro-angiogenetic capabilities which critically support cancer cell survival. Furthermore, our data suggest HRG as a possible prognostic predictor in HCC patients with MASLD/MASH-related HCCs. [ABSTRACT FROM AUTHOR]

Background: Hepatic myofibroblasts (MFs) can originate from hepatic stellate cells, portal fibroblasts, or bone marrow-derived mesenchymal stem cells and can migrate towards the site of injury by aligning with nascent and established fibrotic septa in response to several mediators. OncostatinM (OSM) is known to orchestrate hypoxia-modulated hepatic processes involving the hypoxia-inducible factor 1 (HIF-1). Methods. In vivo and in vitro experiments were performed to analyze the expression of OSM and OSM-receptor (OSMR) in three murine models of non-alcoholic-fatty liver disease (NAFLD) and -steatohepatitis (NASH) and in human NASH patients as well as the action of OSM on phenotypic responses of human MFs. Results: Hepatic OSM and OSMR levels were overexpressed in three murine NASH models and in NASH patients. OSM stimulates migration in human MFs by involving early intracellular ROS generation and activation of Ras/Erk, JNK1/2, PI3K/Akt as well as STAT1/STAT3 pathways and HIF-1α. OSM-dependent migration relies on a biphasic mechanism requiring early intracellular generation of reactive oxygen species (ROS) and late HIF1-dependent expression and release of VEGF. Conclusion: OSM is overexpressed in experimental and human progressive NAFLD and can act as a profibrogenic factor by directly stimulating migration of hepatic MFs. [ABSTRACT FROM AUTHOR]

Objectives: No data are available in the literature on the extent to which the immune host-response and bacterial-elicited inflammation separately contributes to the increase in gingival crevicular fluid (GCF) levels of inflammatory biomarkers in patients affected by desquamative gingivitis (DG) secondary to oral lichen planus (OLP). The aim of this study was to investigate the effect of a structured plaque control intervention on GCF levels of MMP-1 and MMP-9 in OLP patients with DG and to compare them with those of non-OLP patients. Materials and methods: The study population consisted of 18 unrelated Caucasian patients with DG, while 18 periodontally healthy subjects were recruited for the control group. Periodontal parameters and GCF biomarker amounts were evaluated at baseline and 2 months after a structured plaque control intervention, comprising professional oral hygiene sessions, manual toothbrushing, and interdental cleaning advice, only for DG patients. Determination of MMP-1 and MMP-9 levels was carried out by means of an enzyme-linked immunosorbent assay. Results: Plaque control program led to improvement in all examined clinical parameters and resulted in significant decrease in GCF total amount and concentration of MMP-1 and MMP-9 in comparison to baseline (p < 0.001). However, MMP-1 and MMP-9 levels in DG patients were still significantly higher than those in the healthy control group (p < 0.01). Conclusions: These findings would seem to support an intrinsic upregulated expression of MMPs in DG patients that is exacerbated by bacterial plaque. Clinical relevance: The present outcomes provide further scientific grounds for the importance of strict professional oral hygiene sessions in DG patients. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this randomized, parallel‐design, clinical trial was to investigate the effectiveness of an intensive plaque control programme with sonic versus manual toothbrushing on clinical outcomes and gingival crevicular fluid (GCF) levels of matrix metalloproteinases (MMP) in desquamative gingivitis (DG) patients. Methods: A total of 32 patients affected by DG secondary to oral lichen planus (OLP) were consecutively recruited and randomly assigned to a test (n = 16) and control (n = 16) group. Both groups were enrolled in an intensive control programme comprising supragingival scaling and polishing, and brush‐specific instructions for a period of 8 weeks. The treatment of interest (test) was the use of a sonic‐powered toothbrush, and the standard treatment (control) was the utilization of a soft‐bristle manual toothbrush for twice‐daily home oral hygiene procedures. Periodontal parameters, patient‐centred outcomes, MMP‐1 and MMP‐9 GCF levels were evaluated at baseline and 8 weeks after starting the programme. Results: The plaque control programme resulted in statistically significant reduction in periodontal parameters with consequent improvement in the clinical features, painful symptoms and severity of DG lesions in both groups (all P < 0.001). When a sonic toothbrush was used, there was a more significant decrease in clinical indices, mucosal disease scores and GCF levels of MMP‐1 and MMP‐9. Conclusions: This clinical trial reported the effectiveness of a combined protocol based on professional oral hygiene and supervised toothbrushing in OLP patients with DG. The daily use of a sonic toothbrush would seem to perform better in the short term. [ABSTRACT FROM AUTHOR]