Search

Assessing HER2 expression in breast cancer cells holds significant diagnostic and prognostic importance. Traditional methods like immunohistochemistry and in situ hybridization suffer from low sensitivity and misclassification rates. In this frame, techniques such as vibrational microscopies can ensure, together with low costs and analytical speed, both high accuracy and precision. Herein, we propose a combined Raman and SERS approach for characterizing 4 breast cancer cell lines and normal cells with varying HER2 expression levels. We show that Raman spectroscopy offers a promising alternative, providing unique molecular fingerprints for cell types based on their biochemical signatures. Its non-invasive nature and ability to detect subtle changes in cellular metabolism make it ideal for cancer cell analysis. Coupled with machine learning techniques like PCA and LDA, Raman spectroscopy can classify different breast cancer subcategories accurately. Surface Enhanced Raman Scattering (SERS) further enhances sensitivity, allowing the detection of single molecules like HER2 receptors. Overall, our results enable fast screening of cancer subpopulation in terms of HER2 concentration and macromolecule cell content. Integration of Raman spectroscopy with SERS offers precise identification and opens avenues for personalized therapies.

Nucleic acids are essential biomolecules for the functioning of cells. In past years, nucleic acids have been assessing their role in prognostics and diagnostics. The progress of nanotechnology has allowed the fabrication of various type of nanostructured biosensors able to detect them with high sensitivity and specificity. Among the available sensing mechanisms, the sensor technology based on Surface-enhanced Raman Spectroscopy (SERS) is frequently preferred for identifying nucleic acids. In these sensors, natural or synthetic oligonucleotide sequences, acting as probes to hybridize the target molecules, are immobilized on a plasmonic sensing platform. In particular, aptamers, short DNA/RNA sequences, are emerging as new recognition elements for their chemical stability and specificity. Here, we focus on the combination of a specific type of aptamer, a molecular aptamer beacon, and nanostructured SERS biosensors for a sensitive detection of nucleic acids.

In this study, we report the results of two non-invasive optical methods, Raman microscopy (RM) and polarization-sensitive digital holographic imaging (PSDHI), for distinguishing prostate cancer cells from healthy ones. RM reveals cancer cells metabolize glucose faster, storing it as fatty acids and cholesteryl esters in lipid droplets (LDs). On the other hand, PSDHI shows significant morphological changes in LDs in glucose-incubated cancer cells, including number, volume, and refractive index. High birefringence in cancer LDs under perpendicular polarizations was observed, enabling fast discrimination with over 90% accuracy. PSDHI results align closely with Raman microscopy, suggesting its potential as a promising, high-speed technique for cancer screening purposes.

Metastasis stands as the leading cause of mortality among colorectal cancer (CRC) patients. Galunisertib (LY2157299, LY) is a small molecule demonstrating promising anti-cancer effects by targeting the Transforming Growth Factor-beta (TGF-β) pathway. This route plays a pivotal role in initiating the epithelial-to-mesenchymal transition (EMT), a critical process for metastatic spread. Unfortunately, LY chronic treatment causes undesired effects. To mitigate these side effects, nanoscale drug delivery systems have emerged as a transformative approach in cancer treatment, enhancing drug effectiveness while minimizing toxicity. In this study, we introduce a hybrid nanosystem (DNP-AuNPs-LY@Gel) comprising porous diatomite nanoparticles decorated with plasmonic gold nanoparticles (AuNPs), encapsulating LY within a gelatin shell. This multifunctional nanosystem demonstrates efficient LY delivery, EMT reversal in CRC 2D and 3D cultures, and anti-cancer effects in vivo. Moreover, the nanosystem allowed the quantification with sub-femtogram resolution of the drug intracellularly released using surface-enhanced Raman spectroscopy (SERS). The release of LY is triggered by CRC cell acidic microenviroment. Real-time monitoring of drug release at the single-cell level is achieved by analyzing SERS signals of LY within CRC cells. The heightened efficacy of LY delivery through the DNP-AuNPs-LY@Gel complex offers a promising alternative strategy for reducing drug dosages and subsequent undesired effects.

Plasmonic and Photonics applications of superconducting materials, suggested at first by the necessity to minimize the dissipative losses of conventional metals in the high frequency ranges, are topics of growing interest in Optics. In this perspective, GdSr2RuCu2O8-δ (Gd1212) Rutheno-Cuprate Superconductor presents very promising properties, showing both superconducting and magnetically ordered phases coexisting in the same cell. To investigate its features, the fabrication of macroscopic crystallographically oriented samples is necessary. The use of melt texturing techniques has shown to be among the most effective ways to achieve the best characteristics, although the fabrication of high-quality Gd1212 samples is intrinsically difficult. To reach a better understanding of Gd1212 incongruent melting reaction, a series of bulk samples annealed at temperatures below and above the melting temperature was prepared. Raman Microscopy and Mapping performed on molten and re-solidified samples revealed the presence of different phases, corresponding to those identified in our previous studies. These observations were also confirmed by XRD, TGA-DTA, and SEM+EDS characterisations. Secondary phases formation showed a strong dependence on the temperature of the annealing treatments. Susceptibility and magnetization measurements show both superconducting and magnetic transitions and a contribution of different spurious magnetic phases as suggested by EDS.

Here we have developed an advanced surface-enhanced Raman scattering (SERS) platform that enables the ultrasensitive, rapid and highly specific identification of tumour biomarkers in liquid biopsies. Our focus is on the detection of Thyroglobulin (Tg), the most important tumour biomarker for the diagnosis and prognosis of thyroid cancer. Specifically, SERS-active substrates fabricated by nanosphere lithography on chip or on tips of optical fiber (OF) were functionalised with Tg Capture antibodies. Gold nanoparticles were functionalized with Detection antibodies and conjugated with a Raman reporter. The sandwich assay platform was validated in the planar configuration and a detection limit of only 7 pg/ml was successfully achieved. A careful morphological characterisation of the SERS substrates allowed us to strictly correlate the coverage area with the Tg concentration. The same approach was successfully demonstrated in the washout of fine needle aspiration biopsies from cancer patients. The strategy was transferred to the Lab On Fiber (LOF) SERS platform and successfully used to detect Tg concentration. The proposed SERS-enhanced immunoassay platform has proven to be highly versatile and can be used with both microfluidic chip POC devices and SERS-OF-based optrodes to perform sensitive, specific and rapid ex vivo assays for Tg detection in liquid intraoperative biopsies.

Despite extensive research efforts, cancer continues to stand as one of the leading causes of death on a global scale. To gain profound insights into the intricate mechanisms underlying cancer onset and progression, it is imperative to possess methodologies that allow the study of cancer cells at the single-cell level, focusing on critical parameters such as cell morphology, metabolism, and molecular characteristics. These insights are essential for effectively discerning between healthy and cancerous cells and comprehending tumoral progression. Recent advancements in microscopy techniques have significantly advanced the study of cancer cells, with Raman microspectroscopy (RM) emerging as a particularly powerful tool. Indeed, RM can provide both biochemical and spatial details at the single-cell level without the need for labels or causing disruptions to cell integrity. Moreover, RM can be correlated with other microscopy techniques, creating a synergy that offers a spectrum of complementary insights into cancer cell morphology and biology. This review aims to explore the correlation between RM and other microscopy techniques such as confocal fluoresce microscopy (CFM), atomic force microscopy (AFM), digital holography microscopy (DHM), and mass spectrometry imaging (MSI). Each of these techniques has their own strengths, providing different perspectives and parameters about cancer cell features. The correlation between information from these various analysis methods is a valuable tool for physicians and researchers, aiding in the comprehension of cancer cell morphology and biology, unraveling mechanisms underlying cancer progression, and facilitating the development of early diagnosis and/or monitoring cancer progression. [ABSTRACT FROM AUTHOR]

A new, simple digital holography-based polarization microscope for quantitative birefringence imaging of biological cells is presented. As a proof of concept, two different class of cells have been characterized by polarization sensitive digital holographic imaging (PSDHI). These two cases study reported are: differentiation of leukaemia cells and identification of reacted sperm cells. Although further experimentation is necessary, the suggested approach could represent a prospective label-free diagnostic tool for use in biological and medical research and diagnosis.

To control net sodium (Na+) uptake, Arabidopsis plants utilize the plasma membrane (PM) Na+/H+ antiporter SOS1 to achieve Na+ efflux at the root and Na+ loading into the xylem, and the channel-like HKT1;1 protein that mediates the reverse flux of Na+ unloading off the xylem. Together, these opposing transport systems govern the partition of Na+ within the plant yet they must be finely co-regulated to prevent a futile cycle of xylem loading and unloading. Here, we show that the Arabidopsis SOS3 protein acts as the molecular switch governing these Na+ fluxes by favoring the recruitment of SOS1 to the PM and its subsequent activation by the SOS2/SOS3 kinase complex under salt stress, while commanding HKT1;1 protein degradation upon acute sodic stress. SOS3 achieves this role by direct and SOS2-independent binding to previously unrecognized functional domains of SOS1 and HKT1;1. These results indicate that roots first retain moderate amounts of salts to facilitate osmoregulation, yet when sodicity exceeds a set point, SOS3-dependent HKT1;1 degradation switches the balance toward Na+ export out of the root. Thus, SOS3 functionally links and co-regulates the two major Na+ transport systems operating in vascular plants controlling plant tolerance to salinity. [ABSTRACT FROM AUTHOR]

Summary: The actin filaments on the surface of echinoderm oocytes and eggs readily undergo massive reorganization during meiotic maturation and fertilization. In sea urchin eggs, the actin cytoskeletal response to the fertilizing sperm is fast enough to accompany Ca2+ signals and to guide sperm's entry into the egg. Although recent work using live cell imaging technology confirmed changes in the actin polymerization status in fertilized eggs, as was previously shown using light and electron microscopy, it failed to provide experimental evidence of F-actin depolymerization a few seconds after insemination, which is concurrent with the sperm-induced Ca2+ release. In the present study, we applied Raman microspectroscopy to tackle this issue by examining the spectral profiles of the egg's subplasmalemmal regions before and after treating the eggs with actin drugs or fertilizing sperm. At both early (15 s) and late (15 min) time points after fertilization, specific peak shifts in the Raman spectra revealed change in the actin structure, and Raman imaging detected the cytoskeletal changes corresponding to the F-actin reorganization visualized with LifeAct-GFP in confocal microscopy. Our observation suggests that the application of Raman spectroscopy, which does not require microinjection of fluorescent probes and exogenous gene expression, may serve as an alternative or even advantageous method in disclosing rapid subtle changes in the subplasmalemmal actin cytoskeleton that are difficult to resolve. [ABSTRACT FROM AUTHOR]

Aromatase inhibitors (AIs) show promising features as drugs to treat estrogen-responsive breast cancer as they block aromatase activity, the key enzyme in estrogen synthesis. The current AIs approved by the Food and Drug Administration for breast cancer treatment present severe adverse effects. For these reasons, it is important to develop of new AIs that are more specific and sensitive. In this paper, we report the synthesis and the characterization of new nonsteroidal aromatase AIs containing triazoles moieties for the treatment of hormone-dependent breast cancer in post-menopausal women. A new series of 1,2,3-triazole based molecules were successfully synthetized and their chemical structures were determined from the spectral data (FT-IR, 13C NMR, 1H NMR, mass spectroscopy) and micro-analytical data. Additionally, the physical properties of the newly synthesized derivatives were reported. The novel compounds were also tested for their anticancer activity in both breast cancer (MCF7 and T-47D) and normal breast (MCF 10A) cell lines, evaluating their effect on cell proliferation, migration, and invasion. The results revealed that the compounds exhibited promising and specific anti-cancer action. [ABSTRACT FROM AUTHOR]

Nanoscale delivery systems have been investigated for therapy due to their advantages, including the sustained delivery of drugs to cells and reduction of systemic toxicity compared to conventional treatments. However, their application is still hampered by experimental challenges, such as the investigation of the drug release in cells rather than in vitro. Here, we describe a hybrid nanoplatform for monitoring the drug release in living colorectal cancer (CRC) cells by Surface-Enhanced Raman Scattering (SERS). Specifically, the anticancer drug Galunisertib is encapsulated in diatomite nanoparticles (DNPs) decorated by gold nanoparticles (AuNPs) and capped by gelatin. The combination of DNP loading capacities with the Raman enhancement of Galunisertib provided by AuNPs enables bio-imaging and drug delivery without using fluorophores or markers, avoiding fluorescence-quenching issues. Thanks to the Raman enhancement of Galunisertib, the drug release profile is monitored and quantified in living cells by SERS with a femtogram scale resolution. When the gelatin shell is digested by proteases, Galunisertib is released and its SERS spectrum decreases, allowing real-time quantification in CRC cells. The therapeutic efficiency of the Galunisertib delivery platform offers an alternative route for lowering drug dose and toxicity.

The present project aimed to improve our understanding of potential effect of nanocellulose (NC) ingestion on human health, addressing some key objectives set by the European Food Safety Authority (EFSA). In particular, the use and improvement of not yet validated advanced in vitro models of human gut, both static and in tubular microfluidic format, was explored for assessing the interaction of the intestinal epithelium with nanocelluloses. NCs (nanofibers and nanocrystals) were examined as pristine material and upon exposure to digestive fluids and interaction with oro‐gastro‐intestinal enzymes. The NC local effects on the intestinal epithelium were assessed in terms of cytotoxicity, inflammation, and intestinal barrier integrity. Assessment of NC uptake and crossing of intestinal barrier was also explored. A specific focus was on immune reactivity at intestinal barrier site; the complex in vitro models were refined by complementation with primary innate immune cells. Exposure of intestinal tissues to inflammatory cytokines allowed to mimic the effect associated with disease condition and to address inflammation‐induced secondary toxicity. [ABSTRACT FROM AUTHOR]

Several studies have evaluated consumer interest in olive oil as a functional food due to its multiple health benefits, but to date, no author has assessed consumers' additional premium price for a differentiated product enriched with its own polyphenols. This paper aims to investigate which predictors are related to health consciousness by assessing the willingness to pay an additional premium price for olive oil with functional properties. In addition, the study assesses how self-perceived nutritional knowledge affects price levels and interest in olive oil characteristics. The survey was carried out in Italy and the statistical analyses were conducted in two stages: the first adopted an econometric approach to evaluate which variables are related to the additional premium price for the product while in the second stage, inferential statistics were performed to obtain information on the role of self-perceived nutritional knowledge. Based on these outcomes, the prominent role of extrinsic characteristics, such as Geographical Indications (GIs), local attributes and health nutritional information emerged, reaffirming the strong link with the territory and health concerns of modern olive oil consumers. Finally, high self-perceived nutritional knowledge respondents were aware of the antioxidant properties of olive oil and registered the highest price thresholds. [ABSTRACT FROM AUTHOR]

Label-free chemical characterization of single cells is an important aim for biomedical research. Standard Raman spectroscopy provides intrinsic biochemical markers for noninvasive analysis of biological samples but is often hindered by the presence of fluorescence background. In this paper, we present an innovative modulated Raman spectroscopy technique to tilter out the Raman spectra from the fluorescence background. The method is based on the principle that the fluorescence background does not change whereas the Raman scattering is shifted by the periodical modulation of the laser wavelength. Exploiting this physical property and importantly the multichannel lock-in detection of the Raman signal, the modulation technique fulfills the requirements of an effective fluorescence subtraction method. Indeed, once the synchronization and calibration procedure is performed, minimal user intervention is required, making the method online and less time-consuming than the other fluorescent suppression methods. We analyze the modulated Raman signal and shifted excitation Raman difference spectroscopy (SERDS) signal of 2 pro-sized polystyrene beads suspended in a solution of fluorescent dye as a function of modulation rate. We show that the signal-to-noise ratio of the modulated Raman spectra at the highest modulation rate is 3 times higher than the SERDS one. To finally evaluate the real benefits of the modulated Raman spectroscopy, we apply our technique to Chinese hamster ovary ceils (CHO). Specifically, by analyzing separate spectra from the membrane, cytoplasm, and nucleus of CHO cells, we demonstrate the ability of this method to obtain localized sensitive chemical information from cells, away from the interfering fluorescence background. In particular, statistical analysis of the Raman data and classification using PCA (principal component analysis) indicate that our method allows us to distinguish between different cell locations with higher sensitivity and specificity, avoiding potential misinterpretation of the data obtained using standard background procedures. 10.1021/ac9026737

The prevalence of patients affected by end-stage diseases or advanced cancer is increasing due to an aging population and progression in medicine and public healthcare. The burden of symptoms these people suffer in the last months of life often forces them to seek aid in an emergency department. In developed countries, acute care hospital-based services are often better designed to treat acute clinical conditions than to manage the needs of patients with serious chronic diseases. Thus, the palliative care (PC) population poses very real clinical challenges to healthcare professionals who care for them in hospital settings. The authors have formulated four key questions (who, why, when, and how) to address in order to identify a model for providing the best care for these PC patients. The questions are related to: (1) defining people living with serious chronic diseases; (2) managing the challenge of unplanned hospital admission of these people; (3) identifying PC patients among people with serious chronic diseases; and (4) determining the appropriate work of caring for this inpatient PC population. Clinicians need the knowledge, tools, and services to care for these PC patients, and acute care hospitals should plan the work of caring for these inpatients. [ABSTRACT FROM AUTHOR]

Forest mechanisation plays an important role in increasing labour productivity and reducing production costs. This work aims at evaluating various logging scenarios in Calabrian pine high forests, considering technical, economic and environmental aspects. The cut-to-length system was adopted and structured as follows: felling and processing operations were carried out using a medium-sized chainsaw while extraction of the processed material was carried out using three different vehicles for timber extraction: (i) by cable skidder, (ii) by grapple skidder and (iii) by a forwarder. The methodology was based on productivity analysis and production cost analysis, while for environmental performance, the life cycle assessment (LCA) approach was adopted. The selected functional unit (FU) was referred to as 1 h of logging operations. However, to assess the resulting usefulness, further analyses were performed using an alternative FU consisting of 1 m3 of round wood. The study's outcomes show the complexity in achieving an optimal balance between productivity, economic aspects and sustainable management in forest operations. [ABSTRACT FROM AUTHOR]

Innate immune memory, the ability of innate cells to react in a more protective way to secondary challenges, is induced by exposure to infectious and other exogeous and endogenous agents. Engineered nanoparticles are particulate exogenous agents that, as such, could trigger an inflammatory reaction in monocytes and macrophages and could therefore be also able to induce innate memory. Here, we have evaluated the capacity of engineered gold nanoparticles (AuNPs) to induce a memory response or to modulate the memory responses induced by microbial agents. Microbial agents used were in soluble vs. particulate form (MDP and the gram-positive bacteria Staphylococcus aureus ; β-glucan and the β-glucan-producing fungi C. albicans), and as whole microrganisms that were either killed (S. aureus , C. albicans) or viable (the gram-negative bacteria Helicobacter pylori). The memory response was assessed in vitro , by exposing human primary monocytes from 2-7 individual donors to microbial agents with or without AuNPs (primary response), then resting them for 6 days to allow return to baseline, and eventually challenging them with LPS (secondary memory response). Primary and memory responses were tested as production of the innate/inflammatory cytokine TNFα and other inflammatory and anti-inflammatory factors. While inactive on the response induced by soluble microbial stimuli (muramyl dipeptide -MDP-, β-glucan), AuNPs partially reduced the primary response induced by whole microorganisms. AuNPs were also unable to directly induce a memory response but could modulate stimulus-induced memory in a circumscribed fashion, limited to some agents and some cytokines. Thus, the MDP-induced tolerance in terms of TNFα production was further exacerbated by co-priming with AuNPs, resulting in a less inflammatory memory response. Conversely, the H. pylori -induced tolerance was downregulated by AuNPs only relative to the anti-inflammatory cytokine IL-10, which would lead to an overall more inflammatory memory response. These effects of AuNPs may depend on a differential interaction/association between the reactive particle surfaces and the microbial components and agents, which may lead to a change in the exposure profiles. As a general observation, however, the donor-to-donor variability in memory response profiles and reactivity to AuNPs was substantial, suggesting that innate memory depends on the individual history of exposures. [ABSTRACT FROM AUTHOR]

Engineered gold nanoparticles (AuNPs) find application in several fields related to human activities (i.e. , food and cosmetic industry or water purification) including medicine, where they are employed for diagnosis, drug delivery and cancer therapy. As for any material/reagent for human use, the safety of AuNPs needs accurate evaluation. AuNPs are prone to contamination by bacterial endotoxin (lipopolysaccharide, LPS), a potent elicitor of inflammatory responses in mammals. It is therefore important, when assessing AuNP immunosafety and immune-related effects, to discriminate between inflammatory effects intrinsic to the NPs from those caused by an undeliberate and undetected LPS contamination. Detection of LPS contamination in AuNP preparations poses different problems when using the current LPS detection assays, given the general interference of NPs, similar to other particulate agents, with the assay reagents and endpoints. This leads to time-consuming search for optimal assay conditions for every NP batch, with unpredictable results, and to the use in parallel of different assays, each with its weaknesses and unpredictability. Thus, the development of highly sensitive, quantitative and accurate assays able to detect of LPS on AuNPs is very important, in view of their medical applications. Surface-enhanced Raman spectroscopy (SERS) is a label-free, sensitive, chemical-specific, nondestructive and fast technique that can be used to directly obtain molecular fingerprint information and a quantitative analysis of LPS adsorbed on AuNPs. Within this study, we describe the use of SERS for the label-free identification and quantitative evaluation - down to few attograms - of the LPS adsorbed on the surface of 50 nm AuNPs. We thus propose SERS as an efficient tool to detect LPS on the AuNP surface, and as the basis for the development of a new sensitive and specific LPS-detection sensor based on the use of AuNPs and SERS. [ABSTRACT FROM AUTHOR]

The Salt-Overly-Sensitive (SOS) pathway controls the net uptake of sodium by roots and the xylematic transfer to shoots in vascular plants. SOS3/CBL4 is a core component of the SOS pathway that senses calcium signaling of salinity stress to activate and recruit the protein kinase SOS2/CIPK24 to the plasma membrane to trigger sodium efflux by the Na/H exchanger SOS1/NHX7. However, despite the well-established function of SOS3 at the plasma membrane, SOS3 displays a nucleo-cytoplasmic distribution whose physiological meaning is not understood. Here, we show that the N-terminal part of SOS3 encodes structural information for dual acylation with myristic and palmitic fatty acids, each of which commands a different location and function of SOS3. N -myristoylation at glycine-2 is essential for plasma membrane association and recruiting SOS2 to activate SOS1, whereas S -acylation at cysteine-3 redirects SOS3 toward the nucleus. Moreover, a poly-lysine track in positions 7–11 that is unique to SOS3 among other Arabidopsis CBLs appears to be essential for the correct positioning of the SOS2-SOS3 complex at the plasma membrane for the activation of SOS1. The nuclear-localized SOS3 protein had limited bearing on the salt tolerance of Arabidopsis. These results are evidence of a novel S -acylation dependent nuclear trafficking mechanism that contrasts with alternative subcellular targeting of other CBLs by S -acylation. [ABSTRACT FROM AUTHOR]

The interaction between engineered nanoparticles and the bacterial lipopolysaccharide, or endotoxin, is an event that warrants attention. Endotoxin is one of the most potent stimulators of inflammation and immune reactions in human beings, and is a very common contaminant in research labs. In nanotoxicology and nanomedicine, the presence of endotoxin on the nanoparticle surface affects their biological properties leading to misinterpretation of results. This review discusses the importance of detecting the endotoxin contamination on nanoparticles, focusing on the current method of endotoxin detection and their suitability for nanoparticulate materials. Conversely, the capacity of nanoparticles to bind endotoxin can be enhanced by functionalization with endotoxin-capturing molecules, opening the way to the development of novel endotoxin detection assays. [ABSTRACT FROM AUTHOR]

Potassium (K) is closely related to plant water uptake and use and affects key processes in assimilation and growth. The aim of this work was to find out to what extent K supply and enhanced compartmentation might improve water use and productivity when tomato plants suffered from periods of water stress. Yield, water traits, gas exchange, photosynthetic rate and biomass partition were determined. When plants suffered dehydration, increasing K supply was associated with reduction in stomatal conductance and increased water contents, but failed to protect photosynthetic rate. Potassium supplements increased shoot growth, fruit setting and yield under water stress. However, increasing the K supply could not counteract the great yield reduction under drought. A transgenic tomato line with enhanced K uptake into vacuoles and able to reach higher plant K contents, still showed poor yield performance under water stress and had lower K use efficiency than the control plants. With unlimited water supply (hydroponics), plants grown in low-K showed greater root hydraulic conductivity than at higher K availability and stomatal conductance was not associated with leaf K concentration. In conclusion, increasing K supply and tissue content improved some physiological features related to drought tolerance but did not overcome yield restrictions imposed by water stress. [ABSTRACT FROM AUTHOR]

Circular Economy (CE) might be the paradigm to re-conceptualize future agri-food industries and recreate a balanced co-existence of ecological and economic systems. Research is then called to find solutions for transitioning into CE. The current paper will apply the theory of sociotechnical transitions as a framework to build a step by step procedure to analyze and manage agri-food circular economy transitions and support stakeholders involved. The agro-ecological (cultivation and harvesting), agro-industrial (food processing) and consumption (food purchase) subsystems of agri-food supply chains are analysed to address the main challenges for the transition into CE. The current paper final goal is to generate an analytical framework, for practitioners and policy makers, to identify suitable technological, market, coordination and regulative solutions to orient future CE trajectories. [ABSTRACT FROM AUTHOR]