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Abstract The adipose tissue (AT) surrounding breast cancer (BC) plays a pivotal role in cancer progression and represents an optimal source for new biomarker discovery. The aim of this work was to investigate whether specific AT factors may have prognostic value in estrogen receptor-positive (ER+) BC. Proteoglycan Versican (VCAN), Insulin-like Growth Factor 1 (IGF1), Reticulon 4B (RTN4), chemokines CCL5 (also known as RANTES) and interleukin 8 (IL-8) are expressed in AT and may play important roles in BC progression. Peritumoral AT and tumoral biopsies were obtained from patients with ER+ BC (N = 23). AT specimens were collected also from healthy women (N = 17; CTRL-AT). The analysis of gene expression by qPCR revealed significantly higher mRNA levels of VCAN, IGF1, RTN4, and CCL5 in BC-AT compared to the CTRL-AT, and no difference in IL-8 mRNA levels. VCAN positively correlated with patient Body Mass Index (BMI) in BC-AT, while not in CTRL-AT. Moreover, VCAN and IGF1 positively correlated with RTN4 and negatively with CCL5. Interestingly, VCAN correlated with tumoral Ki67, while IGF1 with tumoral OCT4 that, in turn, correlated with tumoral Ki67 and patient BMI. Thus, peritumoral AT content of VCAN, and IGF1 are related to BC proliferation and aggressiveness.

Arturo Cuomo,1,* Ileana Parascandolo2,* 1Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS - Fondazione G Pascale, Naples, Italy; 2Istituto Nazionale Tumori, IRCCS - Fondazione G Pascale, Naples, Italy*These authors contributed equally to this workCorrespondence: Arturo Cuomo, Email a.cuomo@istitutotumori.na.itAbstract: Chronic musculoskeletal pain (CMP), defined as persistent discomfort in musculoskeletal tissues persisting for over 3 months, afflicts an estimated 1.71 billion people globally, leading to significant functional impairments and psychological distress, thereby detrimentally affecting individuals’ quality of life. The objective of this narrative review is to elucidate the complex relationship among dietary habits, sarcopenia, and gut microbiota composition, with an eye toward enhancing patient management and outcomes. Given the burgeoning interest in the influence of diet on CMP, a detailed examination of the current literature is warranted. Nutritional intake is a critical determinant of the gut microbiota profile, which, in turn, is linked to musculature integrity and performance, potentially leading to sarcopenia. The development of sarcopenia can aggravate CMP owing to diminished muscular strength and functionality. Additionally, disruptions in the gut microbiota may directly modulate nociception, intensifying CMP manifestations. Thus, nutritional optimization emerges as a viable approach to CMP management. Emphasizing a diet conducive to a healthy gut microbiome could forestall or mitigate sarcopenia, thereby attenuating CMP intensity. Nevertheless, the domain calls for further empirical exploration to unravel the nuances of these interactions and to forge efficacious dietary strategies for individuals with CMP. Beyond mere analgesia, comprehensive patient care for CMP requires acknowledgment of the complex and multifactorial nature of pain and its foundational elements. Embracing an integrative treatment model allows healthcare practitioners to promise better patient prognoses, enriched life quality, and a decrease in the sustained healthcare costs associated with CMP.Plain Language Summary: Chronic musculoskeletal pain (CMP) is long-lasting pain in the bones, muscles, and joints, and it’s a common problem affecting over 1.7 billion people worldwide. This kind of pain can really disrupt someone’s daily life, making it hard to do everyday things and causing a lot of stress.This review is like a deep dive into how eating habits, muscle loss, and the tiny organisms living in our guts all connect to this pain. As we are becoming more curious about how food affects CMP, it’s important to look closely at what we already know.What we eat can change the tiny bugs in our guts, which has a big impact on our muscles. If our muscles get weak and shrink (a condition called sarcopenia), it can make CMP worse because weak muscles cannot support our bodies well. Also, if the balance of bugs in our gut is off, it might even make us feel pain more intensely. So, changing what we eat might be a good way to tackle CMP. Eating foods that keep our gut bugs happy might help prevent muscle loss and reduce pain. But we still need to do more research to understand this better and to figure out the best foods to eat for this purpose.Treating CMP is not just about getting rid of the pain; it’s about looking at the whole picture and all the things that contribute to the pain. By considering everything — from our diet to our muscles to our gut bugs — doctors can help improve the lives of people with CMP, making them more comfortable and possibly reducing medical costs in the long run.Keywords: chronic musculoskeletal pain, diet, nutrition, treatment, biopsychosocial, holistic

Paraphenylenediamine (PPD) is a well-known culprit allergen in the literature and clinical practice. Although this has been described in temporary tattoos, the definite implication of PPD in permanent tattoos has not been described. We report a patient who developed severe allergic contact dermatitis (ACD) requiring skin grafting after receiving a permanent tattoo with ink containing PPD. A 30-year-old female with a past history of atopic dermatitis and psoriasis presented with a 2-week history of cutaneous reaction to a recent tattoo. The patient noticed inflammation and irritation of the tattoo site the day after administration. The patient was previously identified on patch testing to have a PPD allergy after evaluation for dermatitis after hair dye application. Following the tattoo placement, she applied soap and bacitracin cream which she had used several years prior on a similar tattoo. On presentation 2 weeks later, she was found to have a deep ulcerated plaque with an indurated border encompassing the area of the tattoo. She was referred to the emergency department and admitted for treatment, ultimately requiring debridement and skin grafting. The patient obtained the safety data sheets for the tattoo inks which revealed PPD as an ingredient in every color. We believe this is the first confirmed case of PPD being implicated as the causative agent for ACD to a permanent tattoo. Tattoo ink is unregulated, and formulas are proprietary which makes safe practice difficult for patients with sensitivities. We advocate for consistent ingredient labeling, regulation, and transparency within the tattoo ink industry.

This article reads the technological management of complex and global events, including SARS-CoV-2 pandemic, as part of the transition of European democracies towards control and surveillance models imposed by normal emergencies following one another with increasing frequency. The text reflects on pandemics along history, on the technocratic and digital trajectory of contemporary societies, and concludes by outlining local-based forms of self-government.

Halo-structured nuclei are examples of many-body open quantum system. Here the authors use a complete kinematics measurement and find an elastic breakup of proton halo nucleus 8B.

The proton drip-line nucleus 17Ne is considered a good candidate for a Borromean two-proton halo with a 15O + p + p structure. Angular distributions of the elastic scattering and inclusive 15O production for a 136 MeV 17Ne beam incident on a 208Pb target were measured for the first time at the SPIRAL1 facility, GANIL. Use of the GLORIA detector array allowed high-resolution data over a wide angular range from 20∘ up to 95∘ in the laboratory frame to be obtained. The elastic scattering angular distribution shows similarities with those for both 6He and 20Ne at equivalent collision energies with respect to the corresponding Coulomb barriers, exhibiting the suppression of the Coulomb rainbow peak characteristic of strong coupling. Optical model and coupled channel fits suggest that this is due to a combination of coupling to low-lying quadrupole resonances and Coulomb dipole coupling to the low-lying continuum, although their relative importance depends on the relevant B(E2) values which remain to be firmly determined.

ERK1/2 phosphorylation is frequently downregulated in the early phase of colon tumorigenesis with subsequent activation of ERK5. In the current work, we studied the advantages of ERK1/2 downregulation for tumor growth by dissecting the individual functions of ERK1 and ERK2. The patient sample data demonstrated decreased ERK1/2 phosphorylation in the early phase of tumorigenesis followed by increased phosphorylation in late-stage colon adenocarcinomas with intratumoral invasion or metastasis. In vitro results indicated that SOD3-mediated coordination of small GTPase RAS regulatory genes inhibited RAS-ERK1/2 signaling. In vitro and in vivo studies suggested that ERK2 has a more prominent role in chemotactic invasion, collective migration, and cell proliferation than ERK1. Of note, simultaneous ERK1 and ERK2 expression inhibited collective cell migration and proliferation but tended to promote invasion, suggesting that ERK1 controls ERK2 function. According to the present data, phosphorylated ERK1/2 at the early phase of colon adenocarcinoma limits tumor mass expansion, whereas reactivation of the kinases at the later phase of colon carcinogenesis is associated with the initiation of metastasis. Additionally, our results suggest that ERK1 is a regulatory kinase that coordinates ERK2-promoted chemotactic invasion, collective migration, and cell proliferation. Our findings indicate that ROS, especially H2O2, are associated with the regulation of ERK1/2 phosphorylation in colon cancer by either increasing or decreasing kinase activity. These data suggest that ERK2 has a growth-promoting role and ERK1 has a regulatory role in colon tumorigenesis, which could lead to new avenues in the development of cancer therapy.

Platelet products are commonly used in regenerative medicine due to their effects on the acceleration and promotion of wound healing, reduction of bleeding, synthesis of new connective tissue, and revascularization. Furthermore, a novel approach for the treatment of damaged tissues, following trauma or other pathological damages, is represented by the use of mesenchymal stem cells (MSCs). In dogs, both platelet-rich plasma (PRP) and MSCs have been suggested to be promising options for subacute skin wounds. However, the collection of canine PRP is not always feasible. In this study, we investigated the effect of human PRP (hPRP) on canine MSCs (cMSCs). We isolated cMSCs and observed that hPRP did not modify the expression levels of the primary class of major histocompatibility complex genes. However, hPRP was able to increase cMSC viability and migration by at least 1.5-fold. hPRP treatment enhanced both Aquaporin (AQP) 1 and AQP5 protein levels, and their inhibition by tetraethylammonium chloride led to a reduction of PRP-induced migration of cMSCs. In conclusion, we have provided evidence that hPRP supports cMSC survival and may promote cell migration, at least through AQP activation. Thus, hPRP may be useful in canine tissue regeneration and repair, placing as a promising tool for veterinary therapeutic approaches.

Low-grade chronic inflammation (LGCI) is a common feature of non-communicable diseases. Cytokines play a crucial role in LGCI. This study aimed to assess how LGCI risk factors [e.g., age, body mass index (BMI), smoke, physical activity, and diet] may impact on specific cytokine levels in a healthy population. In total, 150 healthy volunteers were recruited and subjected to questionnaires about the last 7-day lifestyle, including smoking habit, physical activity, and food frequency. A panel of circulating cytokines, chemokines, and growth factors was analyzed by multiplex ELISA. BMI showed the heaviest impact on the correlation between LGCI-related risk factors and cytokines and was significantly associated with CRP levels. Aging was characterized by an increase in IL-1b, eotaxin, MCP-1, and MIP-1α. Smoking was related to higher levels of IL-1b and CCL5/RANTES, while physical activity was related to MIP-1α. Within the different eating habits, CRP levels were modulated by eggs, red meat, shelled fruits, and greens consumption; however, these associations were not confirmed in a multivariate model after adjusting for BMI. Nevertheless, red meat consumption was associated with an inflammatory pattern, characterized by an increase in IL-6 and IL-8. IL-8 levels were also increased with the frequent intake of sweets, while a higher intake of shelled fruits correlated with lower levels of IL-6. Moreover, IL-6 and IL-8 formed a cluster that also included IL-1b and TNF-α. In conclusion, age, BMI, smoke, physical activity, and dietary habits are associated with specific cytokines that may represent potential markers for LGCI.

12C +12 C is the main reaction during core and shell carbon burning in massive stars, however, at temperatures higher than 109K when most of the carbon is depleted and its abundance is lower than 16O, the 12C +16 O fusion can also become relevant. Moreover, 12C +16 O reaction can ignite also in the scenario of explosive carbon burning. The astrophysical energy region of interest thus ranges from 3 to 7.2 MeV in the center-of-mass frame. There are various measurements of the cross-section available in the literature, however, they all stop around 4 MeV, making extrapolation necessary at lower energies. To try to solve this uncertainty and corroborate direct measurement the Trojan Horse Method was applied to three-body processes 16O(14N, α24Mg)2H and 16O(14N, p27Al)2H to study the 16O(12C, α)24Mg and 16O(12C, p)27Al reactions.

Astrophysical reactions involving radioactive isotopes (RI) often play an important role in high-temperature stellar environments. The experimental studies on the reaction rates for those are still limited mainly due to the technical difficulties in producing high-quality RI beams. A direct measurement of those reactions would be still challenging in many cases, however, we can make a reliable evaluation of the reaction rates by an indirect method or by studying the resonance prorerties. Here we ntroduce recent examples of experimental studies on such RI-involving astrophysical reactions, performed at Center for Nuclear Study, the University of Tokyo, using the low-energy RI beam separator CRIB. One is for the neutron-induced destruction reactions of 7Be in the Big-Bang nucleosynthesis, and the other is the study on the 22Mg(α, p) reaction relevant in X-ray bursts, which was performed with the resonant scattering method from the inverse reaction channel.

The carbon-burning process in massive stars mainly occurs via the 12C +12 C. However, at temperatures higher than 109K and considering the increased abundance of 16O produced during the later stages of the heliumburning,the 12C+16O fusion can also become relevant. Moreover, 12C+16O also plays a role in the scenario of explosive carbon burning. Thus, the astrophysical energy region of interest ranges from 3 to 7.2 MeV in the center-of-mass frame. However, the various measurements of the cross-section available in the literature stop around 4 MeV, making extrapolation necessary. To solve this uncertainty and corroborate direct measurement we applied the Trojan Horse Method to three-body processes 16O(14N, α24Mg)2H and 16O(14N, p27Al)2H to study the 12C(16O, α)24Mg and 12C(16O, p)27Al reactions in their entire energy region of astrophysical interest. In this contribution, after briefly describing the method used, the experiment and the preliminary phases of the data analysis will be presented and discussed.

The low-energy light radioactive ion beam in-flight facility EXOTIC and the associated experimental set-up,operational at Legnaro National Laboratories of the National Institute of Nuclear Physics (LNL-INFN, Italy) and designed for nuclear physics and nuclear astrophysics experiments, were described. The outline of the experimental program carried out employing the produced radioactive ion beams was presented and the perspectives of the EXOTIC project were discussed.

The mechanism of reactions with weakly-bound proton-rich nuclei at energies near the Coulomb barrier is a long-standing open question owing to the paucity of experimental data. In this study, a complete kinematics measurement was performed for the proton drip-line nucleus 17F interacting with 58Ni at four energies near the Coulomb barrier. Thanks to the powerful performance of the detector array, exhaustive information on the reaction channels, such as the differential cross sections for quasielastic scattering, exclusive and inclusive breakup, as well as for fusion-evaporation protons and alphas, was derived for the first time. The angular distributions of quasielastic scattering and exclusive breakup can be described reasonably well by the continuum-discretized coupled-channels calculations. The inclusive breakup was investigated using the three-body model proposed by Ichimura, Austern, and Vincent, and results indicate the non-elastic breakup is the dominant component. The total fusion cross sections were determined by the fusion-evaporation protons and alphas. Based on the measured exclusive breakup data, the analysis of the classical dynamical simulation code PLATYPUS demonstrates that the incomplete fusion plays a minor role. Moreover, compared with 16O+58Ni, both the reaction and total fusion cross sections of 17F+58Ni exhibit an enhancement in the sub-barrier energy region, which mainly arises from couplings to the continuum states. This work indicates that the information of full reaction channels is crucially important to comprehensively understand the reaction mechanisms of weakly bound nuclear systems.

This essay offers an analysis of the global situation of food systems, providing a few pointers concerning two interconnected issues: the democratisation of the access to food, and the need to heal the ecological damage caused by centralized and mass systems for production and consumption of merchandise. We approach such phenomena through a multi-scalar prism, interpreting the geographical articulation of social behaviour through a continuous shift from local to global. We focus on the processes of modernization and development of commodity-food that, since last century, took hold in many regions, along with their social and ecological failures. Subsequently, various alternative paths of production, distribution and consumption of food are studied, trying to match the nutritional daily needs of local citizens but also the ecological features of their territories and of the life-supporting systems of our planet. You write food and you read democracy as our most urgent challenge is to recover the capacity to reconcile human and ecological communities. This can only be achieved by renouncing centralized and hierarchical (and anti-democratic by nature) models of commodity management. Ultimately, the most effective ‘therapies’ to heal the current crisis of social and political systems are nestled in those agro-ecological, small-scale farming practices that, by cooling climate, can restore the independence of local communities and their dwellers.

Experimental studies on astrophysical reactions involving radioactive isotopes (RI) often accompany technical challenges. Studies on such nuclear reactions have been conducted at the low-energy RI beam separator CRIB, operated by Center for Nuclear Study, the University of Tokyo. We discuss two cases of astrophysical reaction studies at CRIB; one is for the 7Be+n reactions which may affect the primordial 7Li abundance in the Big-Bang nucleosynthesis, and the other is for the 22Mg(α, p) reaction relevantin X-raybursts.

Background: The aim of this research was to evaluate the effects of three different titanium (Ti) implant surfaces on the viability and secretory functions of mesenchymal stem cells isolated from a Bichat fat pad (BFP-MSCs). Methods: Four different Ti disks were used as substrate: (I) D1: smooth Ti, as control; (II) D2: chemically etched, resembling the Kontact S surface; (III) D3: sandblasted, resembling the Kontact surface; (IV) D4: blasted/etched, resembling the Kontact N surface. BFP-MSCs were plated on Ti disks for 72 h. Cell viability, adhesion on disks and release of a panel of cytokines, chemokines and growth factor were evaluated. Results: BFP-MSCs plated in wells with Ti surface showed a viability rate (~90%) and proliferative rate comparable to cells plated without disks and to cells plated on D1 disks. D2 and D4 showed the highest adhesive ability. All the Ti surfaces did not interfere with the release of cytokines, chemokines and growth factors by BFP-MSCs. However, BFP-MSCs cultured on D4 surface released a significantly higher amount of Granulocyte Colony-Stimulating Factor (G-CSF) compared either to cells plated without disks and to cells plated on D1 and D2. Conclusions: The implant surfaces examined do not impair the BFP-MSCs cell viability and preserve their secretion of cytokines and chemokines. Further in vitro and in vivo studies are necessary to define the implant surface parameters able to assure the chemokines’ optimal release for a real improvement of dental implant osseointegration.

Superoxide dismutase (SOD) family isoenzymes, SOD1, SOD2, and SOD3, synthesize hydrogen peroxide (H2O2), which regulates the signal transduction. H2O2 is a second messenger able to enter into the cells through aquaporin 3 cell membrane channels and to modify protein tyrosine phosphatase activity. SOD3 has been shown to activate signaling pathways in tissue injuries, inflammation, and cancer models. Similar to the H2O2 response in the cells, the cellular response of SOD3 is dose-dependent; even a short supraphysiological concentration reduces the cell survival and activates the growth arrest and apoptotic signaling, whereas the physiological SOD3 levels support its growth and survival. In the current work, we studied the signaling networks stimulated by SOD3 overexpression demonstrating a high diversity in the activation of signaling cascades. The results obtained suggest that SOD3, although inducing cell growth and affecting various biological processes, does not cause detectable long-term DNA aberrations. Therefore, according to the present data, SOD3 is not a mutagen. Additionally, we compared SOD3-driven immortalized mouse embryonic fibroblasts to SV40 immortalized NIH3T3 cells, demonstrating a marked difference in the activation of cellular kinases. The data presented may contain important druggable targets to abrogate unwanted cell growth.