Biology subjects

Malavasi, F.

Publications and source records attributed to Malavasi, F..

3 recordsLinked to original sources

bioRxiv2025

Role of Hypertrophic Adipocytes, Collagen VI and CD38 in Fat Fibrosis of Patients with Obesity

Fat fibrosis correlates to metabolic consequences in patients with obesity, and is due to three types of collagen: I and III (fibrillar) and VI (non-fibrillar). In this sudy the extent of fibrosis in obese patients (n 50) was significant only in visceral parenchymal fat (4.7% vs 2.5% in controls (n 15) P<0.0001) and not in subcutaneous fat. Electron microscopy, in vivo and in vitro data, suggested that obese adipocytes are responsible for fibrillar collagen (I and III) production. COL6 (gene producing the non fibrillar form) resulted less expressed. In line, patients with COL6 mutations, showed increased fibrotic tissue even in subcutaneous fat: about 6.5 times vs controls in the patient with the severe form (Ullrich) and 2.8 times in two patients with the milder form (Bethlem). Approximately 15% of obese adipocytes were dead (perilipin1 negative), and consequent infiltrating macrophages showed hyperexpression of CD38, an ectoenzyme implicated in systemic fibrosis. Correlations with gene expression confirmed the importance also of myofibroblasts and the extracellular matrix peptidase D. All together our data support a role for obese adipocytes in the fibrillar collagen production and evidentiate collagen VI and CD38 as new molecular determinants, reinforcing the idea of a multi-factorial origin of fat fibrosis.

cell biology↗

bioRxiv2019

The Creative Mind: Blending Oxytocinergic, Dopaminergic and Personality

In a fast-changing world, creative thinking (CT) is an extraordinary currency. Oxytocin (OT) is associated with CT and release of OT depends on ADP ribosyl-cyclases (CD38 and CD157). Moreover, CT as well as OTs mechanism of action are mediated via central dopaminergic pathways. Consequently, we evaluate the roles of CD38, CD157, dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) peripheral gene expression in CT. Two principal domains of CT, divergent thinking and insight solving problems, were assessed using validated behavioral assessments. To facilitate discriminant validity, two established correlates of CT, trait Openness and fluid intelligence as well as age and sex were included in the regression model. In women, significant main effects (p<0.01) were positively associated with the expression CD38, CD15, and their interaction CD38 x CD157 controlling for Openness, fluid intelligence and age. Subsequent analysis on the subscale-level revealed significant main effects for CD157 and CD38 x CD157 in men specifically for divergent thinking. In women, significant (p<0.01) results are also observed for dopaminergic expression (DRD2, COMT, DRD2 x COMT). The full model (oxytocinergic and dopaminergic gene expressions, Openness, and fluid intelligence) explains a sizable 39% of the variance in females. Significant main effects are observed for CD38, CD157, DRD2 and COMT as well as their interactions (CD38xCD157 and DRD2xCOMT). In conclusion, we show that oxytocinergic and dopaminergic gene expression contribute significantly to the complex CT phenotype suggesting the notion that the perspective gained from examining the peripheral transcriptome meaningfully adds to understanding the landscape of creative thinking.\n\nSignificance StatementCreative thinking (CT) is a powerful driving force galvanizing progress and civilization. Towards better understanding the neurobiology of CT, we implement a gene expression strategy that is considered to capture not only genomic elements but also environmental signatures. We employ laboratory measures of CT (alternative uses test and insight problem solving), controlling for fluid intelligence and the personality trait of Openness. We focus on oxytocinergic and dopaminergic genes that contribute to the molecular architecture of CT. Oxytocinergic and dopaminergic gene expression significantly explains a robust 39% of the variance in CT. Notably, this study demonstrates the potential of the peripheral transcriptome towards tracing gene pathways underlying some complex cognitive behaviors such as creative thinking.

neuroscience↗

bioRxiv2019

CD38 is a good predictor of anti-PD-1 immunotherapy responsiveness in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated mortality in the world. However, with the associated low five-year survival and high recurrence rates, alternative treatment modalities specifically immunotherapy have been researched. A correlation between CD38+ tumour-infiltrating leukocyte (TIL) density and improved prognosis was found in a recent study. However, studies relating to CD38 expression in immune infiltrates within tumours are limited. In the present study, we confirmed the expression of CD38 on macrophages in HCC and determined the relationship between CD38+ leukocytes and lymphocytes and patient response to immunotherapy. Using immunohistochemistry, we analysed tissue samples obtained from 20 patients from Singapore with HCC prior to immunotherapy. Tumour infiltrating leukocytes expression within tumour were correlated to the responsiveness of patients to immunotherapy.\n\nExpression of CD38 was found within the tumour cells and surrounding immune infiltrates including lymphocytes and macrophages. We then ask whether CD38 expression by the distinct cell populations may acquire theranostic relevance. Patients with higher level of CD38+ immune infiltrate subsets had significantly better response to anti-PD-1 immunotherapy, and this is also true for CD38+ lymphocytes within the tumour microenvironment. In particular, a cut-off of 13.0% positive out of total leukocytes and 12.4% positive out of total lymphocytes is found to be of strong predictive value of responsiveness to immunotherapy treatment, thus a strong theranostic impact is seen by using CD38 as a biomarker for anti-PD-1 therapy.\n\nThe establishment of an association between CD38 expression and the response to anti-PD-1 immunotherapy in HCC, could be applied to a larger cohort outside Singapore. These may eventually change the routine testing in clinical practice to identify HCC patients suitable for immunotherapy.

cancer biology↗