Stefania Pucciarelli

Fat reduction in cheese remains a major technological challenge due to the critical role of milk fat in structuring the protein matrix and modulating flavor release. Limited information is available on the use of fat replacers in short-ripened cheeses, where rapid matrix reorganization strongly influences texture and aroma development. This study investigated the effect of inulin (2.5% and 5%) as a fat replacer on the physicochemical, biochemical, and sensory properties of low-fat Caciotta cheese during 21 days of ripening. Inulin was completely retained within the cheese matrix under conventional processing conditions. Matrix composition significantly affected lipolysis, resulting in reduced free fatty acid formation in inulin-enriched samples. These modifications influenced the generation and partitioning of volatile compounds. Sensory evaluation indicated improved quality at 2.5% inulin, whereas higher levels caused excessive softening. Overall, matrix organization was identified as a key factor governing texture and aroma development in short-ripened, low-fat cheese systems.

This paper explores the concept of alterity within “ethical” meat production and consumption, focusing on small-scale producers and consumers in a rural Mediterranean context. Drawing on a relational understanding of alterity as a process through which actors negotiate difference within capitalist foodscapes, the study examines how ethical commitments and socio-material practices co-produce what counts as “alternative.” Using qualitative interviews with producers of “ethical meat” and their consumers from a solidarity-based Alternative Food Network (AFN) in Le Marche (Italy), the paper investigates how producer–consumer relations, animal welfare, and ecological care are interlinked within an ethical meatscape. Despite differing perceptions of the AFN’s role, embodied exchanges and face-to-face trust emerge as key to sustaining ethical and environmentally conscious practices. By capturing the micro-social dynamics through which relational alterity is enacted, the paper contributes to debates on sustainable agri-food transitions and socio-environmental justice, showing how ethical and ecological outcomes are co-produced through human and more-than-human relations.

Lung cancers that harbor wild type KRAS (KRAS-WT) represent a molecularly diverse subset of tumors that often lack targeted therapeutic options. Using synthesized gold(I)-based inhibitors, a multi-omics approach, and functional validation, we identified Thioredoxin reductase 1 (TXNRD1), encoding as a selective vulnerability in KRAS-WT and oncogenic KRAS mutant (KM)-independent lung cancer (LC). Mechanistically, TRXR1 blockade induces ferroptosis through glutathione depletion, lipid reactive oxygen species (ROS) accumulation, and HMOX1-dependent iron overload in KRAS-WT LC both in vitro and in vivo. Furthermore, while KM LC cells are intrinsically resistant to TRXR1 inhibition, KMLC cells that acquire resistance to KRAS inhibitors (KRASi) undergo a redox shift that renders them sensitive to TRXR1 inhibition, uncovering a potential novel therapeutic vulnerability in KRASi-refractory tumors. These findings establish TRXR1 as a targetable redox checkpoint in KRAS-WT and KRASi-resistant lung cancers and support further development of TRXR1 inhibitors.

Inonotus obliquus (Chaga) is a medicinal mushroom with several pharmacological properties that is used as a tea in traditional Chinese medicine. In this study, Chaga water extract was digested in vitro to mimic the natural processing and absorption of its biocomponents when it is consumed as functional beverage, and its anticancer activities were evaluated in breast cancer (BC) cell lines, representing HER2-positive and triple-negative subtypes. After chemical characterization by liquid chromatography/mass spectrometry (HR-QTOF) analysis, the effect of Chaga biocomponents on cell viability and cell cycle progression was assessed by MTT assay, FACS analysis, and Western blot. Dihydrofolate reductase (DHFR) activity was measured by an enzymatic assay. Four highly bioactive triterpenoids (inotodiol, trametenolic acid, 3-hydroxy-lanosta-8,24-dien-21-al, and betulin) were identified as the main components, able to decrease BC cell viability and block the cell cycle in G0/G1 by inducing the downregulation of cyclin D1, CDK4, cyclin E, and phosphorylated retinoblastoma protein. DHFR was identified as their crucial target. Moreover, bioactive Chaga components exerted a synergistic action with cisplatin and with trastuzumab in SK-BR-3 cells by inhibiting both HER2 and HER1 activation and displayed an immunomodulatory effect. Thus, Inonotus obliquus represents a source of triterpenoids that are effective against aggressive BC subtypes and display properties of targeted drugs.

Lung cancer is a leading cause of cancer-related death worldwide that needs updated therapies to contrast both the serious side effects and the occurrence of drug resistance. A panel of non-small cell lung cancer (NSCLC) cells were herein employed as cancer models. Eight structurally related gold(I) and gold(III) complexes with NHC and halides or triphenylphosphane ligands were investigated as lung cancer cell growth inhibitors. As expected, gold compounds with PPh₃ were found to be more cytotoxic than homoleptic [(NHC)₂-Au(I)]X or heteroleptic NHC-Au(I)X or NHC-Au(III)X₃ complexes. Mixed ligand gold(I) compounds exhibiting the linear NHC-AuPPh₃ (compound 7) or the trigonal NHC-Au(Cl)PPh₃ (compound 8) arrangements at the central metal were found to be the best lung cancer cytotoxic compounds. Analysis of the TrxR residual activity of the treated cells revealed that these compounds efficiently inhibit the most accredited molecular target for gold compounds, the TrxR, with compound 8 reaching more than 80% activity reduction in lung cells. Some of the current cancer lung therapy protocols consist of specific lung cancer cell cytotoxic agents combined with antifolate drugs; interestingly, the herein gold compounds are both TrxR and antifolate inhibitors. The human DHFR was inhibited with IC₅₀ ranging between 10–21 µM, depending on substrate concentrations, proceeding by a likely allosteric mechanism only for compound 8.

The study of the impact of polyQ expansion driven proteotoxicity on cell metabolism has evi-denced NAD molecule as a central player in regulating metabolic response and cell repair in neurodegeneration. The decline in NAD intracellular levels represents a hallmark of ageing aris-ing from a dysregulation between NAD-consuming and biosynthetic enzymatic reactions in which NMNAT plays a key role. By an integrated bioanalytical and proteomic experimental design, the derangement of NAD metabolism deriving from the accumulation of polyQ-Htt protein has been analysed in Saccha-romices cerevisiae harbouring a 103Q-Htt and compared with wild-type Htt, in absence and in presence of a phenolic extract from EVOO, as a source of antioxidant bioactive compounds. Quantification of NAD and its precursors and proteomic analysis of the differential protein ex-pression has been performed by LC-DAD-MS. Chronological lifespan and NAD homeostasis was strongly impaired by proteotoxic polyQ-Htt, eliciting a depletion of NAD levels and accumulation of NaMN. In parallel a downregulation of Sirt2 expression levels has been observed. Phenolic extract administration had no meaningful ef-fects on NAD replenishment to prevent proteotoxicity. NaMN can represent a biomarker of accel-erated aging, and/or a signaling molecule for cell repair.

Acute diarrhea is a very frequent condition affecting dogs; nevertheless, little is known about what happens in the GI tract during such conditions. Proteomics allows the study of proteins present in a specific biologic substrate, and fecal proteomic investigations have been recently implemented to study GI diseases in dogs. In the present study, the fecal protein profiles of eight dogs suffering from acute uncomplicated diarrhea at the time of inclusion was investigated for the first time, and then the same patients were followed, replicating two further evaluations at two subsequent time points (after 2 and 14 days from the first presentation), with the aim of gaining possible new insights regarding the pathologic changes in the gastrointestinal environment during such conditions. Two-dimensional gel electrophoresis (2-DE) was performed, followed by mass spectrometry. Nine spots, corresponding to four (groups of) proteins (i.e., albumin, alkaline phosphatase, chymotrypsin-C-like, and some immunoglobulins), showed significant differences at two or more of the three time points investigated, almost all behaving similarly and decreasing at T1 (2 days after the onset of the condition) and significantly increasing at T2 (14 days after the onset), mainly evidencing a reaction of the organism. Further studies including a greater number of patients and possibly different techniques are needed to confirm the present findings.

Breast cancers (BCs) may present dramatic diagnoses, both for ineffective therapies and for the limited outcomes in terms of lifespan. For these types of tumors, the search for new drugs is a primary necessity. It is widely recognized that gold compounds are highly active and extremely potent as anticancer agents against many cancer cell lines. The presence of the metal plays an essential role in the activation of the cytotoxicity of these coordination compounds, whose activity, if restricted to the ligands alone, would be non-existent. On the other hand, gold exhibits a complex biochemistry, substantially variable depending on the chemical environments around the central metal. In this review, the scientific findings of the last 6–7 years on two classes of gold(I) compounds, containing phosphane or carbene ligands, are reviewed. In addition to this class of Au(I) compounds, the recent developments in the application of Auranofin in regards to BCs are reported. Auranofin is a triethylphosphine-thiosugar compound that, being a drug approved by the FDA—therefore extensively studied—is an interesting lead gold compound and a good comparison to understand the activities of structurally related Au(I) compounds.