L’Accademia delle Scienze, con il patrocinio dell’Alma Mater Studiorum - Università di Bologna, promuove una serie di incontri volta ad analizzare il percorso scientifico compiuto dalle diverse aree di ricerca dislocate entro il perimetro dell’Alma Mater, nel periodo che corre dai primi anni Cinquanta agli esordi del XXI secolo. L’intento dell’iniziativa non è quello dell’autocelebrazione di una fase che è stata indubbiamente molto positiva nella vita plurisecolare del nostro ateneo, ma di porre in evidenza gli esiti che ha conseguito la sua ricerca sul piano nazionale e internazionale; le reti scientifiche che intorno a queste attività sono nate e si sono sviluppate; l’attività formativa che ne è seguita; i rapporti con le imprese, le amministrazioni pubbliche e altri comparti della vita civile cittadina e regionale. Questa ricognizione, che non è solo di memoria, si propone anche l’obiettivo di segnalare i possibili livelli di crescita e di intersezione tra le frontiere della scienza e della tecnologia e le esigenze della vita poiché la ricerca e la formazione sono chiamate a svolgere compiti molto rilevanti nella società della conoscenza.

Supplementary Table 1, Figures 1-4 from Oncogenic Role of miR-483-3p at the IGF2/483 Locus

Supplementary Table 3 from Cyclin G1 Is a Target of miR-122a, a MicroRNA Frequently Down-regulated in Human Hepatocellular Carcinoma

ST1: Discovery and validation surgical patient cohorts. ST2: Advanced HCC patient cohort. ST3: Primer sequences for luciferase assay. ST4: Primer sequences for PCR and qPCR. ST5: Antibodies. ST6: Probe sequences for EMSA. ST7: Deregulated miR-30 family members in rat model.

1Professor of Radiology, Northeastern Ohio Medical University, Southwoods Imaging, Youngstown, Ohio 44512 2Honorary Professor of the University of Bologna, Italy 3President of the Academy of Sciences of Bologna, Italy, Strada Maggiore 48, Bologna, 4015 Correspondence Honorary Professor of the University of Bologna, Italy, President of the Academy of Sciences of Bologna, Italy, Strada Maggiore 48, Bologna, 4015. Email: [email protected]

Supplementary Table 1 from MiR-122/Cyclin G1 Interaction Modulates p53 Activity and Affects Doxorubicin Sensitivity of Human Hepatocarcinoma Cells

Supplementary Table 1 from Cyclin G1 Is a Target of miR-122a, a MicroRNA Frequently Down-regulated in Human Hepatocellular Carcinoma

Supplementary Table S1. Characteristics of surgical HCC patients analysed in this study. Supplementary Table S2. Patients assessed for circulating miR-221. Supplementary Table S3. Primer sequences and PCR conditions for the cloning experiment. Supplementary Table S4. Primer sequences and PCR conditions. Supplementary Table S5. Antibodies used in Western blot analysis.

Supplementary Table 3 from MiR-199a-3p Regulates mTOR and c-Met to Influence the Doxorubicin Sensitivity of Human Hepatocarcinoma Cells

Introduction: The burden of metabolic (dysfunction) associated fatty liver disease (MAFLD) is rising mirrored by an increase in hepatocellular cancer (HCC). MAFLD and its sequelae are characterized by perturbations in lipid handling, inflammation, and mitochondrial damage. The profile of circulating lipid and small molecule metabolites with the development of HCC is poorly characterized in MAFLD and could be used in future studies as a biomarker for HCC. Methods: We assessed the profile of 273 lipid and small molecule metabolites by ultra-performance liquid chromatography coupled to high-resolution mass spectrometry in serum from patients with MAFLD (n = 113) and MAFLD-associated HCC (n = 144) from six different centers. Regression models were used to identify a predictive model of HCC. Results: Twenty lipid species and one metabolite, reflecting changes in mitochondrial function and sphingolipid metabolism, were associated with the presence of cancer on a background of MAFLD with high accuracy (AUC 0.789, 95% CI: 0.721–0.858), which was enhanced with the addition of cirrhosis to the model (AUC 0.855, 95% CI: 0.793–0.917). In particular, the presence of these metabolites was associated with cirrhosis in the MAFLD subgroup (p < 0.001). When considering the HCC cohort alone, the metabolic signature was an independent predictor of overall survival (HR 1.42, 95% CI: 1.09–1.83, p < 0.01). Conclusion: These exploratory findings reveal a metabolic signature in serum which is capable of accurately detecting the presence of HCC on a background of MAFLD. This unique serum signature will be taken forward for further investigation of diagnostic performance as biomarker of early stage HCC in patients with MAFLD in the future.

Microarray analysis, cell transfection and infection, cell proliferation assay, clonogenic and sphere formation assays, TP53 hypothetical binding sites.

Figure S4. (A, E) Box plot graphs of serum AFP in HCC patients with high and low miR-221 or caspase-3 expression levels. High and low miR-221 or caspase-3 expression was identified on the basis of the median value.

Figure S2. Histopathological images of HCC nodules arisen in DEN-treated rats following Sorafenib administration. Nodules that responded to Sorafenib displayed large necrotic areas.

Supplementary Figure Legends 1-4 from MiR-122/Cyclin G1 Interaction Modulates p53 Activity and Affects Doxorubicin Sensitivity of Human Hepatocarcinoma Cells

<p>Supplementary Material and Methods, Results, 1 figure, and 1 table</p>

Supplementary Material and Methods, Results, 1 figure, and 1 table

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) has been traditionally associated with insulin resistance and obesity. Recently, pollutants have been shown to contribute to the development of MASLD. Given the global burden of MASLD, understanding whether pollutants are merely associated with steatosis or contribute to its progression to advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC) is critical. Workers exposed to occupational toxicants represent an ideal population for assessing the potentially hazardous consequences of professional exposure. Confirming a link between occupational exposure and ACLD/HCC may provide further elements in understanding MASLD and contribute to preventive strategies for exposed workers.AimThis study aimed to assess the prevalence of self-reported occupational exposure to toxicants in patients with MASLD.MethodsThis hospital-based prospective pilot study included 201 patients with MASLD. Data on workplace toxicant exposure were collected systematically using a structured questionnaire. Subsequently, patients with ACLD and/or HCC (n=55) were compared to controls (n=146). Logistic regression analysis and propensity score models were used to investigate the associations between self-reported occupational exposure and ACLD and/or HCC.ResultsPatients with ACLD/HCC reported exposure to metals, halogenated refrigerants, pain/resins, and fuel emissions more often than the controls. After controlling for confounders, durations of 21–30 years and >30 years of occupational exposure to toxicants showed odds ratios (ORs) of 2.31 (95% confidence interval [CI]: 1.09–4.88, p=0.029) and 4.47 (95% CI: 2.57–7.78, p<0.001), respectively.ConclusionsIn this pilot study, patients with MASLD complications were more likely to report workplace toxicant exposure. Our results warrant future multicentre confirmatory studies, as implementing prevention policies may reduce the risk of life-threatening diseases among exposed populations.

Supplementary Table 4 from Cyclin G1 Is a Target of miR-122a, a MicroRNA Frequently Down-regulated in Human Hepatocellular Carcinoma

Figure S1. Schematic flow chart of HCC patients.