14 research outputs found
Investigating why online purchasing push offline sales in the luxury market
The digital revolution has led to major changes, both in the luxury market, which has been a traditional one for thousands of years, and in the luxury customer experience, which is now affected by omnichannel retailing and requires a perfect integration between online and offline channels. Luxury firms have been slower than many non- luxury firms to adopt online digital marketing, but today the trends show that online purchasing contribute to overall market growth more than cannibalizing and continue to grow. This study lays the foundations for investigating the factors affecting luxury consumers’ behaviour in the digital era, as the online sales contributes to global sales and push offline purchases
The Fragile X Mental Retardation Protein Regulates RIPK1 and Colorectal Cancer Resistance to Necroptosis
Background & aims: The fragile X mental retardation protein (FMRP) affects multiple steps of the mRNA metabolism during brain development and in different neoplastic processes. However, the contribution of FMRP in colon carcinogenesis has not been investigated.
Methods: FMR1 mRNA transcript and FMRP protein expression were analyzed in human colon samples derived from patients with sporadic colorectal cancer (CRC) and healthy subjects. We used a well-established mouse model of sporadic CRC induced by azoxymethane to determine the possible role of FMRP in CRC. To address whether FMRP controls cancer cell survival, we analyzed cell death pathway in CRC human epithelial cell lines and in patient-derived colon cancer organoids in presence or absence of a specific FMR1 antisense oligonucleotide or siRNA.
Results: We document a significant increase of FMRP in human CRC relative to non-tumor tissues. Next, using an inducible mouse model of CRC, we observed a reduction of colonic tumor incidence and size in the Fmr1 knockout mice. The abrogation of FMRP induced spontaneous cell death in human CRC cell lines activating the necroptotic pathway. Indeed, specific immunoprecipitation experiments on human cell lines and CRC samples indicated that FMRP binds receptor-interacting protein kinase 1 (RIPK1) mRNA, suggesting that FMRP acts as a regulator of necroptosis pathway through the surveillance of RIPK1 mRNA metabolism. Treatment of human CRC cell lines and patient-derived colon cancer organoids with the FMR1 antisense resulted in up-regulation of RIPK1.
Conclusions: Altogether, these data support a role for FMRP in controlling RIPK1 expression and necroptotic activation in CRC
Rafoxanide sensitizes colorectal cancer cells to TRAIL-mediated apoptosis
Colorectal cancer (CRC) remains a leading causes of cancer-related death in the world, mainly due to the lack of effective treatment of advanced disease. TNF-related apoptosis-inducing ligand (TRAIL)-driven cell death, a crucial event in the control of tumor growth, selectively targets malignant rather than non-transformed cells. However, the fact that cancer cells, including CRC cells, are either intrinsically resistant or acquire resistance to TRAIL, represents a major hurdle to the use of TRAIL-based strategies in the clinic. Agents able to overcome CRC cell resistance to TRAIL have thus great therapeutic potential and many researchers are making efforts to identify TRAIL sensitizers. The anthelmintic drug rafoxanide has recently emerged as a potent anti-tumor molecule for different cancer types and we recently reported that rafoxanide restrained the proliferation of CRC cells, but not of normal colonic epithelial cells, both in vitro and in a preclinical model mimicking sporadic CRC. As these findings were linked with the induction of endoplasmic reticulum stress, a phenomenon involved in the regulation of various components of the TRAIL-driven apoptotic pathway, we sought to determine whether rafoxanide could restore the sensitivity of CRC cells to TRAIL. Our data show that rafoxanide acts as a selective TRAIL sensitizer in vitro and in a syngeneic experimental model of CRC, by decreasing the levels of c-FLIP and survivin, two key molecules conferring TRAIL resistance. Collectively, our data suggest that rafoxanide could potentially be deployed as an anti-cancer drug in the combinatorial approaches aimed at overcoming CRC cell resistance to TRAIL-based therapies
The Impact of Customer Education on the Perception of Made in Italy Products in the Agri-Food Sector
While the global COVID-19 pandemic affected all the industries, the Italian agri-food sector positively performed over this period, supported by the exports, underlining the need for new international strategies to authentically engage consumers.This study aims to investigate the impact of customer education (CE) on the perceptions and evaluations of foreign consumers towards Made in Italy products as a part of the food experience in the agri-food sector. After a literature review, the paper illustrates the main topics of customer education, food experience and country-of-origin (COO) effect of Made in Italy. The purposes of the conceptual paper relate to the strategic use of country-of-origin effect by companies in order to promote products and services in foreign markets, and to the analysis of the impact of customer education within the food sector on the perception of Made in Italy products taking into account the new challenges of the current situation
How process accumulation knowledge enables circular business model: a case study
The Waste of Electrical and Electronic Equipment industry is gaining primary importance within the circular economy, but its implementation is facing internal and external barriers. This paper shows how knowledge-accumulation favours the transition to circular-business-models in a traditional sector. It focuses on the internal barrier related to knowledge and technology and shows a successful overcome within the case study of Astelav Ri-Generation project. The company was able to make the transition to a circular-business-model, preserving the value of the product and achieving economic, environmental and social benefits. The research methodology proposes a holistic single-case study approach, multiple source of evidence have been used to collect different types of data. The study shows that the transition to a circular-business-model is not easy as it appears, but it is a long and complex process that requires accumulation of knowledge and its correct strategic application in the changing competitive environment
Dynamic innovation for sustainability in the luxury apparel industry
Sustainability in the luxury fashion industry is increasingly at the forefront of major brands’ marketing. Yet, achieving environmental and social sustainability in apparel products is virtually impossible without actions upstream in the supply-chain. In this article, we study the role of first tier suppliers in introducing sustainability-driven innovations in the industry. With an in-depth case study of an Italian B2B luxury “fashion engineering” company, we map the systematic introduction of new sustainability practices and innovations, that gradually built internal know-how regarding sustainability. The process moved from innovations in processes, to the supply-chain, and lastly to the product level, spanning organizational, operational, and communication practices. We find that the company could sustain significant growth over the past decade also thanks to its sustainable innovations, which have become more ambitious and effective thanks to the learning-by-doing embedded in this dynamic trajectory
Targeted Therapy of Interleukin-34 as a Promising Approach to Overcome Cancer Therapy Resistance
Chemotherapy and immunotherapy have markedly improved the management of several malignancies. However, not all cancer patients respond primarily to such therapies, and others can become resistant during treatment. Thus, identification of the factors/mechanisms underlying cancer resistance to such treatments could help develop novel effective therapeutic compounds. Tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) are major components of the suppressive tumor microenvironment and are critical drivers of immunosuppression, creating a tumor-promoting and drug-resistant niche. In this regard, therapeutic strategies to tackle immunosuppressive cells are an interesting option to increase anti-tumor immune responses and overcome the occurrence of drug resistance. Accumulating evidence indicates that interleukin-34 (IL-34), a cytokine produced by cancer cells, and/or TAMs act as a linker between induction of a tumor-associated immunosuppressive microenvironment and drug resistance. In this article, we review the current data supporting the role of IL-34 in the differentiation/function of immune suppressive cells and, hence, in the mechanisms leading to therapeutic resistance in various cancers
Toward negative CO2 emissions and circular carbon economy by carbonization of low-value organic waste in the presence of zinc- based molten salts
Catalytic carbonization in molten salts offers a new and emerging technology approach for treating organic wastes to achieve negative CO2 emissions and a circular carbon economy by converting the low-value carbon content of the waste into high value solid carbon materials which can be reused, and also converting the hydrogen content of the waste into a low-carbon hydrogen-rich fuel gas. In the work herein, the use of pure molten ZnCl2 in batch reactors was studied for this purpose. A proper reaction apparatus was designed and realized. The ZnCl2 was provided by VWR Chemicals (>97% of purity) and C16-C18 saturated hydrocarbons and synthetic polyolefins were used as model compounds to carry out a preliminary investigation of the effect of kinetic severity, tuned by changing reaction temperature and time, on the performances of the process evaluated in terms of yield of gaseous hydrogen and solid carbon in the residue. TGA analyses of pure ZnCl2 and high density polyethylene (HDPE) and of their binary mixtures demonstrated the catalytic activity of ZnCl2 made evident by an improvement of the mass loss rate. Exploratory carbonization experiments of high density polyethylene showed that, when the reaction temperature increased from 300 to 380 °C for 30 min, the gaseous H2 yield increased from 0,3% to 1,1 %w/w, the limiting theoretical value being 14% w/w. When the reaction time was further increased from 30 min to 3 h an enhancement in the production of light olefins in the place of hydrogen
was observed. Preliminary results indicate that ZnCl2 can catalyze the carbonization of polyolefins
Hepcidin Upregulation in Colorectal Cancer Associates with Accumulation of Regulatory Macrophages and Epithelial–Mesenchymal Transition and Correlates with Progression of the Disease
Advanced, metastatic colorectal cancer (CRC) is associated with high rate of mortality because of its poor responsiveness to chemotherapy/immunotherapy. Recent studies have shown that hepcidin, a peptide hormone produced mainly by hepatocytes, is expressed by and enhances the growth of tumor cells. We here assessed whether hepcidin expression helps identify subsets of CRC with advanced and aggressive course. By integrating results of in vitro/ex vivo studies with data of bioinformatics databases, we initially showed that hepcidin RNA and protein expression was more pronounced in tissue samples taken from the tumor area, as compared to the macroscopically unaffected, adjacent, colonic mucosa of CRC patients. The induction of hepcidin in the colonic epithelial cell line HCEC-1ct by interleukin (IL)-6, IL-21 and IL-23 occurred via a Stat3-dependent mechanism and, in primary CRC cells, hepcidin co-localized with active Stat3. In CRC tissue, hepcidin content correlated mainly with macrophage accumulation and IL-10 and CD206 expression, two markers of regulatory macrophages. Consistently, both IL-10 and CD206 were up-regulated by hepcidin in blood mononuclear cells. The highest levels of hepcidin were found in metastatic CRC and survival analysis showed that high expression of hepcidin associated with poor prognosis. Moreover, hepcidin expression correlated with markers of epithelial-to-mesenchymal transition and the silencing of hepcidin in CRC cells reduced epithelial-to-mesenchymal transition markers. These findings indicate that hepcidin is markedly induced in the advanced stages of CRC and suggest that it could serve as a prognostic biomarker in CRC
An essential role of adenosine deaminase acting on RNA 1 in coeliac disease mucosa
Background and aimType I interferons (IFNs) are highly expressed in the gut mucosa of celiac disease (CD) gut mucosa and stimulates immune response prompted by gluten ingestion, but the processes that maintain the production of these inflammatory molecules are not well understood. Adenosine deaminase acting on RNA 1 (ADAR1), an RNA-editing enzyme, plays a crucial role in inhibiting self or viral RNAs from activating auto-immune mediated responses, most notably within the type-I IFN production pathway. The aim of this study was to assess whether ADAR1 could contribute to the induction and/or progression of gut inflammation in patients with celiac disease.Material and methodsADAR1 expression was assessed by Real time PCR and Western blotting in duodenal biopsy taken from inactive and active celiac disease (CD) patients and normal controls (CTR). To analyze the role of ADAR1 in inflamed CD mucosa, lamina propria mononuclear cells (LPMC) were isolated from inactive CD and ADAR1 was silenced in with a specific antisense oligonucleotide (AS) and then incubated with a synthetic analogue of viral dsRNA (poly I:C). IFN-inducing pathways (IRF3, IRF7) in these cells were evaluated with Western blotting and inflammatory cytokines were evaluated with flow cytometry. Lastly, the role of ADAR1 was investigated in a mouse model of poly I:C-driven small intestine atrophy.ResultsReduced ADAR1 expression was seen in duodenal biopsies compared to inactive CD and normal controls. Ex vivo organ cultures of duodenal mucosal biopsies, taken from inactive CD patients, stimulated with a peptic-tryptic digest of gliadin displayed a decreased expression of ADAR1. ADAR1 silencing in LPMC stimulated with a synthetic analogue of viral dsRNA strongly boosted the activation of IRF3 and IRF7 and the production of type-I IFN, TNF-α and IFN-γ. Administration of ADAR1 antisense but not sense oligonucleotide to mice with poly I:C-induced intestinal atrophy, significantly increased gut damage and inflammatory cytokines production.ConclusionsThese data show that ADAR1 is an important regulator of intestinal immune homeostasis and demonstrate that defective ADAR1 expression could provide to amplifying pathogenic responses in CD intestinal mucosa