Business models and organizational structures of family-owned wineries in Italy

The main goal of this study is to analyse the family business organizational structure and how wineries family firms operate in the market. The socioemotional wealth model (SEW) has been used to represent the non-financial goals and utilities of family owned firms. In this regard, a survey was proposed. Finally, to investigate the development and current state of research on image and reputation in family firms, a systematic literature review has been conducted

Sintesi e caratterizzazione di nuovi cluster triangolari di Platino

Scopo del presente lavoro di tesi è la sintesi di architetture molecolari composte da cluster trinucleari di platino alternati da spaziatori organici od organometallici, lo studio della corrispondente reattività, nonché delle proprietà ottiche, magnetiche, elettriche di tali derivati. All’interno di tale progetto s’inserisce il tentativo di utilizzare come bulding blocks cluster trinucleari di platino magneticamente attivi con numero di elettroni di valenza dispari (NEV) e l’eventuale caratterizzazione dei medesimi. Nella sintesi dei derivati verranno utilizzati diversi leganti carbenici, e terpiridine funzionalizzate come spaziatori, a partire dal precursore [Pt3(u-PBut2)3(CO)3]+CF3SO3-

Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells

Β-blockers (BB) are a primary treatment for chronic heart disease (CHD), resulting in prognostic and symptomatic benefits. Cardiac cell therapy represents a promising regenerative treatment and, for autologous cell therapy, the patients clinical history may correlate with the biology of resident progenitors and the quality of the final cell product. This study aimed at uncovering correlations between clinical records of biopsy-donor CHD patients undergoing cardiac surgery and the corresponding yield and phenotype of cardiospheres (CSs) and CS-derived cells (CDCs), which are a clinically relevant population for cell therapy, containing progenitors. We describe a statistically significant association between BB therapy and improved CSs yield and CDCs phenotype. We show that BB-CDCs have a reduced fibrotic-like CD90 + subpopulation, with reduced expression of collagen-I and increased expression of cardiac genes, compared to CDCs from non-BB donors. Moreover BB-CDCs had a distinctive microRNA expression profile, consistent with reduced fibrotic features (miR-21, miR-29a/b/c downregulation), and enhanced regenerative potential (miR-1, miR-133, miR-101 upregulation) compared to non-BB. In vitro adrenergic pharmacological treatments confirmed cytoprotective and anti-fibrotic effects of β1-blocker on CDCs. This study shows anti-fibrotic and pro-commitment effects of BB treatment on endogenous cardiac reparative cells, and suggests adjuvant roles of β-blockers in cell therapy applications

The IMiDs targets IKZF-1/3 and IRF4 as novel negative regulators of NK cell-activating ligands expression in multiple myeloma

Immunomodulatory drugs (IMiDs) have potent anti-tumor activities in multiple myeloma (MM) and are able to enhance the cytotoxic function of natural killer (NK) cells, important effectors of the immune response against MM. Here, we show that these drugs can enhance the expression of the NKG2D and DNAM-1 activating receptor ligands MICA and PVR/CD155 in human MM cell lines and primary malignant plasma cells. Depletion of cereblon (CRBN) by shRNA interference strongly impaired upregulation of these ligands and, more interestingly, IMiDs/CRBN-mediated downregulation of the transcription factors Ikaros (IKZF1), Aiolos (IKZF3) and IRF4 was critical for these regulatory mechanisms. Indeed, shRNA knockdown of IKZF1 or IKZF3 expression was both necessary and sufficient for the upregulation of MICA and PVR/CD155 expression, suggesting that these transcription factors can repress these genes; accordingly, the direct interaction and the negative role of IKZF1 and IKZF3 proteins on MICA and PVR/CD155 promoters were demonstrated. Finally, MICA expression was enhanced in IRF4-silenced cells, indicating a specific suppressive role of this transcription factor on MICA gene expression in MM cells. Taken together, these findings describe novel molecular pathways involved in the regulation of MICA and PVR/CD155 gene expression and identify the transcription factors IKZF-1/IKZF-3 and IRF4 as repressors of these genes in MM cells

Hepatic adrenal rest tumor in a patient with multifactorial liver cirrhosis: a case report with CT and MRI findings and pathologic correlation

AbstractBackgroundAdrenal rest tumor is an ectopic collection of adrenocortical cells in an extra-adrenal site, more frequently located around the kidney, retroperitoneum, spermatic cord, para-testicular region and broad ligament, but very rarely occurring also in the liver. Hepatic adrenal rest tumor poses a diagnostic challenge in differentiating it from hepatocellular carcinoma, particularly in a cirrhotic liver.Case presentationAn 83-years-old male was referred to our hospital by his family doctor for hepatological evaluation due to multifactorial liver cirrhosis. Ultrasound revealed a centimetric hypoechoic nodule in the VI hepatic segment in the context of a liver with signs of cirrhosis and steatosis. The patient first underwent MRI and then CT, which showed a fat containing focal liver lesion in the subcapsular location of the right lobe, strictly adjacent to the homolateral adrenal gland. The nodule was hypervascular in the arterial phase, washed out in the portal-venous and transitional phases, resulting hypointense in the hepato-biliary phase at MR imaging. In the suspicion of a hepatocellular carcinoma, the nodule was surgically removed, and the patient's postoperative course was unremarkable. The final histopathological diagnosis was of adrenal rest tumor of the liver.ConclusionsHepatic adrenal rest tumor is an extremely rare hepatic tumor, often without any clinical manifestation, that can also occur in the cirrhotic liver as in our case. Although there are not specific imaging findings, the possible diagnosis of HART should be considered when we observe a well-defined lesion in the subcapsular location of the right lobe, with fat containing, hypervascularity after contrast medium injection and vascular supply from the right hepatic artery

Genotoxic stress modulates the release of exosomes from multiple myeloma cells capable of activating NK cell cytokine production: role of HSP70/TLR2/NF-kB axis

Exosomes are a class of nanovesicles formed and released through the late endosomal compartment and represent an important mode of intercellular communication. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Here, we investigated whether genotoxic stress could promote the release of exosomes from multiple myeloma (MM) cells and studied the immunomodulatory properties they exert on NK cells, a major component of the antitumor immune response playing a key role in the immunosurveillance of MM. Our findings show that melphalan, a genotoxic agent used in MM therapy, significantly induces an increased exosome release from MM cells. MM cell-derived exosomes are capable of stimulating IFNg production, but not the cytotoxic activity of NK cells through a mechanism based on the activation of NF-kB pathway in a TLR2/ HSP70-dependent manner. Interestingly, HSP70 positive exosomes are primarily found in the bone marrow (BM) of MM patients suggesting that they might have a crucial immunomodulatory action in the tumor microenvironment. We also provide evidence that the CD56high NK cell subset is more responsive to exosome-induced IFNg production mediated by TLR2 engagement. All together, these findings suggest a novel mechanism of synergism between chemotherapy and antitumor innate immune responses based on the drug-promotion of nanovesicles exposing DAMPs for innate receptors

Neuroprotective Effects of IGF-I against TNFα-Induced Neuronal Damage in HIV-Associated Dementia

AbstractHuman immunodeficiency virus type 1 (HIV-1) infection often results in disorders of the central nervous system, including HIV-associated dementia (HAD). It is suspected that tumor necrosis factor-α (TNFα) released by activated and/or infected macrophages/microglia plays a role in the process of neuronal damage seen in AIDS patients. In light of earlier studies showing that the activation of the insulin-like growth factor I receptor (IGF-IR) exerts a strong neuroprotective effect, we investigated the ability of IGF-I to protect neuronal cells from HIV-infected macrophages. Our results demonstrate that the conditioned medium from HIV-1-infected macrophages, HIV/CM, causes loss of neuronal processes in differentiated PC12 and P19 neurons and that these neurodegenerative effects are associated with the presence of TNFα. Furthermore, we demonstrate that IGF-I rescues differentiated neurons from both HIV/CM and TNFα-induced damage and that IGF-I-mediated neuroprotection is strongly enhanced by overexpression of the wt IGF-IR cDNA and attenuated by the antisense IGF-IR cDNA. Finally, IGF-I-mediated antiapoptotic pathways are continuously functional in differentiated neurons exposed to HIV/CM and are likely supported by TNFα-mediated phosphorylation of IκB. All together these results suggest that the balance between TNFα and IGF-IR signaling pathways may control the extent of neuronal injury in this HIV-related experimental setting

The impact of environmental factors in influencing epigenetics related to oxidative states in the cardiovascular system

Oxidative states exert a significant influence on a wide range of biological and molecular processes and functions. When their balance is shifted towards enhanced amounts of free radicals, pathological phenomena can occur, as the generation of reactive oxygen species (ROS) in tissue microenvironment or in the systemic circulation can be detrimental. Epidemic chronic diseases of western societies, such as cardiovascular disease, obesity, and diabetes correlate with the imbalance of redox homeostasis. Current advances in our understanding of epigenetics have revealed a parallel scenario showing the influence of oxidative stress as a major regulator of epigenetic gene regulation via modification of DNA methylation, histones, and microRNAs. This has provided both the biological link and a potential molecular explanation between oxidative stress and cardiovascular/metabolic phenomena. Accordingly, in this review, we will provide current insights on the physiological and pathological impact of changes in oxidative states on cardiovascular disorders, by specifically focusing on the influence of epigenetic regulation. A special emphasis will highlight the effect on epigenetic regulation of human's current life habits, external and environmental factors, including food intake, tobacco, air pollution, and antioxidant-based approaches. Additionally, the strategy to quantify oxidative states in humans in order to determine which biological marker could best match a subject's profile will be discussed

Microglia reactivity entails microtubule remodeling from acentrosomal to centrosomal arrays

Microglia reactivity entails a large-scale remodeling of cellular geometry, but the behavior of the microtubule cytoskeleton during these changes remains unexplored. Here we show that activated microglia provide an example of microtubule reorganization from a non-centrosomal array of parallel and stable microtubules to a radial array of more dynamic microtubules. While in the homeostatic state, microglia nucleate microtubules at Golgi outposts, and activating signaling induces recruitment of nucleating material nearby the centrosome, a process inhibited by microtubule stabilization. Our results demonstrate that a hallmark of microglia reactivity is a striking remodeling of the microtubule cytoskeleton and suggest that while pericentrosomal microtubule nucleation may serve as a distinct marker of microglia activation, inhibition of microtubule dynamics may provide a different strategy to reduce microglia reactivity in inflammatory disease