Publications by authors named "Federica Riva"

85 Publications

Translational Approach to Induce and Evaluate Verocytotoxic O138 Based Disease in Piglets.

Animals (Basel) 2021 Aug 17;11(8). Epub 2021 Aug 17.

Department of Health, Animal Science and Food Safety "Carlo Cantoni" (VESPA), Università degli Studi di Milano, 26900 Lodi, Italy.

Pig livestock was influenced by several global concerns that imposed a re-thinking of the farming system, which included the reduction in chemical dependency and the development of antimicrobial alternatives. Post-weaning diarrhea and enterotoxaemia caused by are serious threats that are responsible for the economic losses related to mortality, morbidity and stunted growth in weaning piglets. The aim of the study was to set up experimental conditions to simulate the simultaneous outbreak of post-weaning diarrhea and enterotoxaemia in weaned piglets, through verocytotoxic O138 challenge, with a multidisciplinary approach. Eighteen piglets susceptible to F18 VTEC infection were selected by polymerase chain reaction for polymorphism on the fucosyltransferase 1 gene and randomly divided in two experimental groups, non-infected controls (C; = 6) and infected ones (I; = 12) and housed into individual pens at the same environmental conditions for 29 days. At day 20, I pigs were orally inoculated with O138 and fed a high protein ration for 3 days. Zootechnical, clinical, microbiological, histological and immunological parameters were evaluated along the follow up (3 and 9 days). Experimental infection, confirmed by bacteria faecal shedding of the I group, significantly affected the clinical status. The I group showed significantly higher total scores, corresponding to medians of the sum of daily scores from days 1 to 3 (Σ3) and 1 to 9 (Σ9) post infection, epiphora, vitality, hair irregularity, oedema and depression. Histological examination showed evident inflammatory infiltrate of lymphocytes, and follicular hyperplasia in I pigs; in the same group, the immunohistochemical and immunological assays revealed an increase in IgG in the intestinal crypts and CD3-positive T cells in intestinal epithelium. The experimental infection in controlled conditions is crucial for both the evaluation of innovative compounds and the elucidation of the mechanisms associated with the persistence of antibacterial resistant strains. In conclusion, the adopted infection model, carried out on receptor-mediated susceptible piglets, allowed us to identify a discriminative panel of clinical symptoms related to O138 infection, and could be used to assess the protective effect of antibiotic alternatives.
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http://dx.doi.org/10.3390/ani11082415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388622PMC
August 2021

Design and optimization of 3D-bioprinted scaffold framework based on a new natural polymeric bioink.

J Pharm Pharmacol 2021 Aug 17. Epub 2021 Aug 17.

Department of Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia, Italy.

Objectives: This aimed at the design and production of engineered 3D scaffold prototypes using a natural polymeric bioink made of chitosan and poly-γ-glutamic acid with a specific focus on 3D-bioprinting process and on 3D framework geometry.

Methods: Prototypes were produced using a 3D bioprinter exploiting layer-by-layer deposition technology. The 3D scaffold prototypes were fully characterized concerning pore size and size distribution, stability in different experimental conditions, swelling capability, and human dermal fibroblasts viability.

Key Findings: Hexagonal framework combined with biopaper allowed stabilizing the 3-layers structure during process manufacturing and during incubation in cell culture conditions. The stability of 3-layers structure was well preserved for 48 h. Crosslinking percentages of 2-layers and 3-layers prototype were 88.2 and 68.39, respectively. The swelling study showed a controlled swelling capability for 2-layers and 3-layers prototype, ∼5%. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed good biocompatibility of 3-layers prototype and their suitability for preserving 48 h cell viability in 3D cultures. Moreover, a significant increment of absorbance value was measured after 48 h, demonstrating cell growth.

Conclusions: Bioink obtained combining chitosan and poly-γ-glutamic acid represents a good option for 3D bioprinting. A stable 3D structure was realized by layer-by-layer deposition technology; compared with other papers, the present study succeeded in using medical healthcare-grade polymers, no-toxic crosslinker, and solvents according to ICH Topic Q3C (R4).
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http://dx.doi.org/10.1093/jpp/rgab116DOI Listing
August 2021

Placebo Analgesia Does Not Reduce Empathy for Naturalistic Depictions of Others' Pain in a Somatosensory Specific Way.

Cereb Cortex Commun 2021 2;2(3):tgab039. Epub 2021 Jun 2.

Social, Cognitive and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, Faculty of Psychology, University of Vienna, 1010 Vienna, Austria.

The shared representations account postulates that sharing another's pain recruits underlying brain functions also engaged during first-hand pain. Critically, direct causal evidence for this was mainly shown for affective pain processing, while the contribution of somatosensory processes to empathy remains controversial. This controversy may be explained, however, by experimental paradigms that did not direct attention towards a specific body part, or that did not employ naturalistic depictions of others' pain. In this preregistered functional magnetic resonance imaging study, we aimed to test whether causal manipulation of first-hand pain affects empathy for naturalistic depictions of pain in a somatosensory-matched manner. Forty-five participants underwent a placebo analgesia induction in their right hand and observed pictures of other people's right and left hands in pain. We found neither behavioral nor neural evidence for somatosensory-specific modulation of pain empathy. However, exploratory analyses revealed a general effect of the placebo on empathy, and higher brain activity in bilateral anterior insula when viewing others' right hands in pain (i.e., corresponding to one's own placebo hand). These results refine our knowledge regarding the neural mechanisms of pain empathy, and imply that the sharing of somatosensory representations seems to play less of a causal role than the one of affective representations.
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http://dx.doi.org/10.1093/texcom/tgab039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276832PMC
June 2021

Therapeutic and Prophylactic Use of Oral, Low-Dose IFNs in Species of Veterinary Interest: Back to the Future.

Vet Sci 2021 Jun 11;8(6). Epub 2021 Jun 11.

Rete Nazionale di Immunologia Veterinaria, 25125 Brescia, Italy.

Cytokines are important molecules that orchestrate the immune response. Given their role, cytokines have been explored as drugs in immunotherapy in the fight against different pathological conditions such as bacterial and viral infections, autoimmune diseases, transplantation and cancer. One of the problems related to their administration consists in the definition of the correct dose to avoid severe side effects. In the 70s and 80s different studies demonstrated the efficacy of cytokines in veterinary medicine, but soon the investigations were abandoned in favor of more profitable drugs such as antibiotics. Recently, the World Health Organization has deeply discouraged the use of antibiotics in order to reduce the spread of multi-drug resistant microorganisms. In this respect, the use of cytokines to prevent or ameliorate infectious diseases has been highlighted, and several studies show the potential of their use in therapy and prophylaxis also in the veterinary field. In this review we aim to review the principles of cytokine treatments, mainly IFNs, and to update the experiences encountered in animals.
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http://dx.doi.org/10.3390/vetsci8060109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231284PMC
June 2021

The first report on coronavirus disease 2019 (COVID-19) vaccine refusal by patients with solid cancer in Italy: Early data from a single-institute survey.

Eur J Cancer 2021 08 26;153:260-264. Epub 2021 May 26.

Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, Rome, Italy; Dipartimento di Medicina Clinica e Molecolare, Università La Sapienza di Roma, Rome, Italy. Electronic address:

Introduction: Patients with cancer have an increased risk of complications from coronavirus disease 2019 (COVID-19) infection, including death, and thus, they were considered as high-priority subjects for COVID-19 vaccination. We report on the compliance with the COVID-19 vaccine of patients affected by solid tumours.

Materials And Methods: Patients with cancer afferent to Medical Oncology 1 Unit of Regina Elena National Cancer Institute in Rome were considered eligible for vaccination if they were receiving systemic immunosuppressive antitumor treatment or received it in the last 6 months or having an uncontrolled advanced disease. The Pfizer BNT162b2 vaccine was proposed to all candidates via phone or during a scheduled visit. The reasons for refusal were collected by administrating a 6-item multiple-choice questionnaire.

Results: From 1st March to 20th March 2021, of 914 eligible patients, 102 refused vaccination (11.2%, 95% confidence interval [CI] 9.1-13.2). The most frequent (>10%) reasons reported were concerns about vaccine-related adverse events (48.1%), negative interaction with concomitant antitumor therapy (26.7%), and the fear of allergic reaction (10.7%). The refusal rate (RR) after 15th March (date of AstraZeneca-AZD1222 suspension) was more than doubled compared with the RR observed before (19.7% versus 8.6%, odds ratio [OR] 2.60, 95% CI 1.69-3.99; P < 0.0001). ECOG-PS 2 was associated with higher RR compared with ECOG-PS 0-1 (OR 2.94, 95% CI 1.04-8.34; P = 0.04). No statistically significant differences in RR according to other clinical characteristics were found.

Conclusions: Our experience represents the first worldwide report on the adherence of patients with cancer to COVID-19 vaccination and underlines how regulatory decisions and media news spreading could influence the success of the campaign.
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http://dx.doi.org/10.1016/j.ejca.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149194PMC
August 2021

The Long Pentraxin PTX3 Controls Severe Infection.

Front Immunol 2021 20;12:666198. Epub 2021 May 20.

Department of Inflammation and Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy.

is a common pathogen in human sepsis. The emergence of multidrug-resistant strains represents a major clinical challenge in nosocomial and community acquired infections. The long pentraxin PTX3, a key component of humoral innate immunity, is involved in resistance to selected pathogens by promoting opsonophagocytosis. We investigated the relevance of PTX3 in innate immunity against infections using mice and mouse models of severe infections. Local and systemic PTX3 expression was induced following pulmonary infection, in association with the up-regulation of TNF-α and IL-1β. PTX3 deficiency in mice was associated with higher bacterial burden and mortality, release of pro-inflammatory cytokines as well as IL-10 in the lung and systemically. The analysis of the mechanisms responsible of PTX3-dependent control of infection revealed that PTX3 did not interact with , or promote opsonophagocytosis. The comparison of susceptibility of wild-type, and / mice to the infection showed that PTX3 acted in a complement-independent manner. Lung histopathological analysis showed more severe lesions in mice with fibrinosuppurative, necrotizing and haemorrhagic bronchopneumonia, associated with increased fibrin deposition in the lung and circulating fibrinogen consumption. These findings indicate that PTX3 contributes to the control of infection by modulating inflammatory responses and tissue damage. Thus, this study emphasizes the relevance of the role of PTX3 as regulator of inflammation and orchestrator of tissue repair in innate responses to infections.
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http://dx.doi.org/10.3389/fimmu.2021.666198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173212PMC
May 2021

Comparison of the response of mammary gland tissue from two divergent lines of goat with high and low milk somatic cell scores to an experimental Staphylococcus aureus infection.

Vet Immunol Immunopathol 2021 Apr 19;234:110208. Epub 2021 Feb 19.

Università degli Studi di Milano, Dipartimento di Medicina Veterinaria, Via dell'Università, 6, 26900 Lodi, Italy; Cornell University, Animal Heath Diagnostic Center, Quality Milk Production Services, Ithaca, NY, USA.

Mastitis represents one of the major economic and health threats to the livestock sector associated with reduction in milk quality, loss of production and is a major reason for culling. Somatic cell score (SCS) is used as a criterion in breeding programmes to select cows genetically less susceptible to mastitis. The relevance of SCS as a predictor of udder health and susceptibility to mastitis is still untested in goats. In this study, two lines of French Alpine goats selected for extreme breeding values for somatic cell scores, one line with high SCS (HSCS) and the other with low SCS (LSCS), were used to test the hypothesis that the mammary response and function differed between the lines. The aim of the present study was to investigate differences in the early immune response in caprine mammary gland tissues challenged with Staphylococcus aureus, one of the main pathogens responsible for the intra-mammary infection in small ruminants, using transcriptomic and histopathology analyses. The comparison between HSCS and LSCS goat lines, showed differences in the response at the histological level for inflammation, presence of neutrophils and micro-abscess formation, and at the molecular level in the expression of CXCL8, IL-6, NFKBIZ and IL-1β. CXCL8 and CXCL2 genes, which showed a higher level of expression in the experimentally infected HSCS line. The molecular data and histopathology both suggested that following S. aureus infection, mobilization, recruitment, infiltration, and chemotaxis of neutrophil, leads to a more severe inflammation in the HSCS compared to LSCS animals. Our results represent an initial basis for further studies to unravel the genetic basis of early mastitis inflammatory responses and the selection of dairy animals more resistant to bacterial mastitis.
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http://dx.doi.org/10.1016/j.vetimm.2021.110208DOI Listing
April 2021

Characterization of Bacterial Microbiota Composition along the Gastrointestinal Tract in Rabbits.

Animals (Basel) 2020 Dec 26;11(1). Epub 2020 Dec 26.

Department of Veterinary Medicine, University of Milano, Via dell'Università 6, 26900 Lodi, Italy.

The microbiota is extremely important for the animal's health, but, to date, knowledge on the intestinal microbiota of the rabbit is very limited. This study aimed to describe bacterial populations that inhabit the different gastrointestinal compartments of the rabbit: stomach, duodenum, jejunum, ileum, caecum, and colon. Samples of the luminal content from all compartments of 14 healthy New White Zealand rabbits were collected at slaughter and analyzed using next generation 16S rRNA Gene Sequencing. The findings uncovered considerable differences in the taxonomic levels among the regions of the digestive tract. Firmicutes were the most abundant phylum in all of the sections (45.9%), followed by Bacteroidetes in the large intestine (38.9%) and Euryarchaeota in the foregut (25.9%). Four clusters of bacterial populations were observed along the digestive system: (i) stomach, (ii) duodenum and jejunum, (iii) ileum, and (iv) large intestine. Caecum and colon showed the highest richness and diversity in bacterial species, while the highest variability was found in the upper digestive tract. Knowledge of the physiological microbiota of healthy rabbits could be important for preserving the health and welfare of the host as well as for finding strategies to manipulate the gut microbiota in order to also promote productive performance.
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http://dx.doi.org/10.3390/ani11010031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824689PMC
December 2020

Collagen/PCL Nanofibers Electrospun in Green Solvent by DOE Assisted Process. An Insight into Collagen Contribution.

Materials (Basel) 2020 Oct 22;13(21). Epub 2020 Oct 22.

Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.

Collagen, thanks to its biocompatibility, biodegradability and weak antigenicity, is widely used in dressings and scaffolds, also as electrospun fibers. Its mechanical stability can be improved by adding polycaprolactone (PCL), a synthetic and biodegradable aliphatic polyester. While previously collagen/PCL combinations were electrospun in solvents such as hexafluoroisopropanol (HFIP) or trifluoroethanol (TFE), more recently literature describes collagen/PCL nanofibers obtained in acidic aqueous solutions. A good morphology of the fibers represents in this case still a challenge, especially for high collagen/PCL ratios. In this work, thanks to preliminary rheological and physicochemical characterization of the solutions and to a Design of Experiments (DOE) approach on process parameters, regular and dimensionally uniform fibers were obtained with collagen/PCL ratios up to 1:2 and 1:1 w/w. Collagen ratio appeared relevant for mechanical strength of dry and hydrated fibers. WAXS and FTIR analysis showed that collagen denaturation is related both to the medium and to the electrospinning process. After one week in aqueous environment, collagen release was complete and a concentration dependent stimulatory effect on fibroblast growth was observed, suggesting the fiber suitability for wound healing. The positive effect of collagen on mechanical properties and on fibroblast biocompatibility was confirmed by a direct comparison of nanofiber performance after collagen substitution with gelatin.
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http://dx.doi.org/10.3390/ma13214698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659940PMC
October 2020

Another's pain in my brain: No evidence that placebo analgesia affects the sensory-discriminative component in empathy for pain.

Neuroimage 2021 01 22;224:117397. Epub 2020 Sep 22.

Social, Cognitive and Affective Neuroscience Unit, Department of Cognition, Emotion, and Methods in Psychology, Faculty of Psychology, University of Vienna, Liebiggasse 5, 1010 Vienna, Austria. Electronic address:

The shared representations account of empathy suggests that sharing other people's emotions relies on neural processes similar to those engaged when directly experiencing such emotions. Recent research corroborated this by showing that placebo analgesia induced for first-hand pain resulted in reduced pain empathy and decreased activation in shared neural networks. However, those studies did not report any placebo-related variation of somatosensory engagement during pain empathy. The experimental paradigms used in these studies did not direct attention towards a specific body part in pain, which may explain the absence of effects for somatosensation. The main objective of this preregistered study was to implement a paradigm overcoming this limitation, and to investigate whether placebo analgesia may also modulate the sensory-discriminative component of empathy for pain. We induced a localized, first-hand placebo analgesia effect in the right hand of 45 participants by means of a placebo gel and conditioning techniques, and compared this to the left hand as a control condition. Participants underwent a pain task in the MRI scanner, receiving painful or non-painful electrical stimulation on their left or right hand, or witnessing another person receiving such stimulation. In contrast to a robust localized placebo analgesia effect for self-experienced pain, the empathy condition showed no differences between the two hands, neither for behavioral nor neural responses. We thus report no evidence for somatosensory sharing in empathy, while replicating previous studies showing overlapping brain activity in the affective-motivational component for first-hand and empathy for pain. Hence, in a more rigorous test aiming to overcome limitations of previous work, we again find no causal evidence for the engagement of somatosensory sharing in empathy. Our study refines the understanding of the neural underpinnings of empathy for pain, and the use of placebo analgesia in investigating such models.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117397DOI Listing
January 2021

The Role of Innate Immune Response and Microbiome in Resilience of Dairy Cattle to Disease: The Mastitis Model.

Animals (Basel) 2020 Aug 11;10(8). Epub 2020 Aug 11.

Institute of Biology and Biotechnology in Agriculture, National Research Council (CNR), 26900 Lodi, Italy.

Animal health is affected by many factors such as metabolic stress, the immune system, and epidemiological features that interconnect. The immune system has evolved along with the phylogenetic evolution as a highly refined sensing and response system, poised to react against diverse infectious and non-infectious stressors for better survival and adaptation. It is now known that high genetic merit for milk yield is correlated with a defective control of the inflammatory response, underlying the occurrence of several production diseases. This is evident in the mastitis model where high-yielding dairy cows show high disease prevalence of the mammary gland with reduced effectiveness of the innate immune system and poor control over the inflammatory response to microbial agents. There is growing evidence of epigenetic effects on innate immunity genes underlying the response to common microbial agents. The aforementioned agents, along with other non-infectious stressors, can give rise to abnormal activation of the innate immune system, underlying serious disease conditions, and affecting milk yield. Furthermore, the microbiome also plays a role in shaping immune functions and disease resistance as a whole. Accordingly, proper modulation of the microbiome can be pivotal to successful disease control strategies. These strategies can benefit from a fundamental re-appraisal of native cattle breeds as models of disease resistance based on successful coping of both infectious and non-infectious stressors.
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http://dx.doi.org/10.3390/ani10081397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459693PMC
August 2020

Full-Digital Workflow for Fabricating a Custom-Made Direct Metal Laser Sintering (DMLS) Mandibular Implant: A Case Report.

Int J Environ Res Public Health 2020 04 14;17(8). Epub 2020 Apr 14.

Department of Dental Sciences, University Vita Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy.

Direct Laser Metal Sintering (DLMS) is an additive manufacturing (AM) technique that is capable of manufacturing metal parts according to a three-dimensional (3D) design made using computer-assisted-design (CAD) software, thanks to a powerful laser beam that melts selectively micro-powder layers, one on top of the other, until the desired object is generated. With DMLS, it is now possible to fabricate custom-made titanium implants for oral and maxillofacial applications. We present the case of a 67-year-old woman diagnosed with a squamous cell carcinoma of the mandible. The patient underwent subtotal mandibular resection; conventional reconstruction procedures failed to rehabilitate the function of the mandible. A prosthesis replacing the resected mandible was designed and fabricated using a digital workflow. The extensive bone defect was rehabilitated with a prosthesis replacing the mandibular bone and supporting a morse-taper dental prosthesis. The masticatory function was reestablished.
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http://dx.doi.org/10.3390/ijerph17082693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215385PMC
April 2020

Remodeling of collagen constituting interlobular septa of subcutaneous adipose tissue following microwaves application.

Dermatol Ther 2020 05 8;33(3):e13362. Epub 2020 Apr 8.

Department of Public Health, Experimental and Forensic Medicine, Unit of Histology and Embryology, University of Pavia, Pavia, Italy.

In this study, the application of a recently introduced device based on electromagnetic energy transfer by microwaves for fat reduction, permitted to study specifically the modifications of thick fibrous collagen interlobular septa in the subcutaneous adipose tissue, related to the formation of large clusters of adipocytes. The use of Picrosirius red staining associated with circularly polarized microscopy gave evidence of appreciable modifications of the fibrous connective tissue forming septa. Compact fibrotic bundles of collagen I forming interlobular septa appeared reduced or dissolved, in part substituted by the increase of more diffuse and finely reticular collagen III. Remodeling of fibrous collagen, which formed bridles involved in the appearance at the surface of the skin of dimpling/orange peer pattern typical of cellulite, was observed.
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http://dx.doi.org/10.1111/dth.13362DOI Listing
May 2020

The Prophylactic Use of Bovine Colostrum in a Murine Model of TNBS-Induced Colitis.

Animals (Basel) 2020 Mar 15;10(3). Epub 2020 Mar 15.

Department of Veterinary Medicine, University of Milano, Via dell'Università 6, 26900 Lodi, Italy.

This study investigated the effects of a short-term administration of bovine colostrum (BC) in a TNBS model of induced colitis. Colitis was induced by TNBS treatment after seven days of BC (BC group, n = 12) or saline (control group, n = 12) administration in mice. Clinical signs, histopathological characteristics, expression levels of Toll-like receptor 4 (TLR4), pro- and anti-inflammatory cytokines, and microbial composition were assessed. BC was well tolerated and did not induce any histological damage or clinical symptoms. After TNBS treatment, the BC group showed a reduction in body weight (BW) loss compared to Control ( < 0.05). Moreover, expression levels of TLR4 ( < 0.01), Interleukin-1β (IL-1β; < 0.001), Interleukin-8 (IL-8; < 0.001), and Interleukin-10 (IL-10; < 0.001) were lower in mice administered with BC. Finally, were higher ( < 0.05), while Enterococci ( < 0.001), spp. ( < 0.001), and spp. ( < 0.05) were lower in Control than BC group. This study confirms that pre-treatment with BC modulates the expression of genes and the count of microbes involved in the etiopathogenesis of colitis.
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http://dx.doi.org/10.3390/ani10030492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143345PMC
March 2020

On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation.

Pharmaceutics 2020 Mar 13;12(3). Epub 2020 Mar 13.

Department Drug Sciences, University of Pavia, V.le Taramelli 12, 27100 Pavia, Italy.

In this study, an innovative microfluidics-based method was developed for one-step synthesis of hyaluronic acid (HA)-based nanoparticles (NPs), by exploiting polyelectrolytic interactions between HA and chitosan (CS), in order to improve reliability, reproducibility and possible scale-up of the NPs preparation. The on-chip synthesis, using a staggered herringbone micromixer, allowed to produce HA/CS NPs with tailored-made size and suitable for both parenteral (117.50 ± 4.51 nm) and loco-regional (349.15 ± 38.09 nm) administration, mainly composed by HA (more than 85% wt) with high negative surface charge (< -20 mV). HA/CS NPs were successfully loaded with a challenging water-insoluble molecule, Everolimus (EVE), an FDA- and EMA-approved anticancer drug able to lead to cell cycle arrest, reduced angiogenesis and promotion of apoptosis. HA/CS NPs resulted to be massively internalized in CD44+ human mesenchymal stem cells via CD44 receptor-mediated endocytosis. HA/CS NPs selectiveness towards CD44 was highlighted by blocking CD44 receptor by anti-CD44 primary antibody and by comparison to CS-based NPs cellular uptake. Eventually, high effectiveness in inhibiting cell proliferation was demonstrated on-chip synthetized EVE loaded HA/CS NPs by tracking in vitro DNA synthesis.
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http://dx.doi.org/10.3390/pharmaceutics12030260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151101PMC
March 2020

Floods, Hurricanes, and Other Catastrophes: A Challenge for the Immune System of Livestock and Other Animals.

Front Vet Sci 2020 31;7:16. Epub 2020 Jan 31.

Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, Milan, Italy.

Climate change involves different dramatic phenomena including desertification and wildfires, severe storms such as hurricanes and blizzards, increased sea levels resulting in flooding coastal cities and rise of atmospheric CO concentration. The alteration of the climate in a specific region affects the life of indigenous animals and humans. The climate changes influence living beings both directly and indirectly. The immune system of animals dramatically suffers the climate instability, making animals more susceptible to infectious and not infectious diseases. Different species of livestock animals respond with similar mechanisms to global warming, but some of them are more susceptible depending on their age, metabolism, and genetic conditions. The selection and study of autochthonous species and breeds, more easily adapted to specific environmental conditions could be an interesting strategy to face livestock rearing in the future.
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http://dx.doi.org/10.3389/fvets.2020.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004950PMC
January 2020

Effects of Diets Enriched in Linseed and Fish Oil on the Expression Pattern of Toll-Like Receptors 4 and Proinflammatory Cytokines on Gonadal Axis and Reproductive Organs in Rabbit Buck.

Oxid Med Cell Longev 2020 21;2020:4327470. Epub 2020 Jan 21.

Department of Veterinary Medicine, University of Milano, 20133 Milano, Italy.

Infections of the genital tract can perturb the fertility in humans and animals. Pathogen recognition and activation of innate immunity onset through the pattern recognition receptor activation, such as Toll-like receptor 4 (TLR4), leading to the production of proinflammatory cytokines and mediators. TLR4 is expressed both on leukocytes and nonimmune cells. Rabbit TLR4 shows great similarity to its human counterpart. Moreover, the TLR4 signalling pathway could be modulated by long-chain polyunsaturated fatty acids (LC-PUFA). The objectives of this study were (i) to determine the expression levels of TLR4 and proinflammatory cytokines in the reproductive hypothalamic-gonadal axis of the male rabbit and (ii) to evaluate if the n-3 PUFA-enriched diets can modify their expression levels in the tissues and LC-PUFA profiles in seminal plasma. Fifteen rabbit bucks ( = 5/experimental group) were fed with different diets: commercial standard (group C), rich in extruded linseed (10%, group L), and in fish oil (3%, group FO) for 110 days. TLR4, TNF-, and IL-1 mRNA were ubiquitously expressed throughout the hypothalamic-gonadal axis. However, TLR4 mRNA expression was lower in the hypothalamus than the epididymis ( < 0.01), seminal vesicles ( < 0.01), and pituitary gland ( < 0.05). Dietary enrichment in PUFA did not modify the gene expression profile nor the histological characteristics of the tissues. Conversely in seminal plasma, rabbits fed with L and FO had lower n-6 ( < 0.05), LC-PUFA n-6 ( < 0.05), and n-6/n-3 ratio ( < 0.05) but higher n-3 ( < 0.001) and LC-PUFA n-3 ( < 0.01) compared to the control group. Our study builds a map of the gene expression of TRL4 and proinflammatory cytokines in the reproductive hypothalamic-gonadal axis of the male rabbit, fundamental step for understanding the immune defence mechanisms. Diets enriched in LC-PUFA did not affect basal gene expression but modulated sperm fatty acid composition. Finally, rabbit may be an excellent animal model to study the relationship between inflammation and infertility, and the nutritional modulation of immune functions.
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http://dx.doi.org/10.1155/2020/4327470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996712PMC
September 2020

Indocyanine Green Loaded Polymeric Nanoparticles: Physicochemical Characterization and Interaction Studies with Caco-2 Cell Line by Light and Transmission Electron Microscopy.

Nanomaterials (Basel) 2020 Jan 11;10(1). Epub 2020 Jan 11.

Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy.

Biomedical applications of nanoparticles (NPs) have reached an increasing development in recent years. Recently, we demonstrated that newly synthesized poly (ethyl 2-cyanoacrylate) nanoparticles (PECA-NPs) are possible antitumor agents due to their cytotoxicity for cancer cells. Indocyanine green (ICG), an amphiphilic tricarbocyanine fluorescent dye, is widely used for the detection of tumoral extension in different organs during clinical surgery. Moreover, this fluorescent agent is unstable and it has a rapid clearance in physiological conditions in vivo. In this study, ICG was charged in PECA-NPs to improve its aqueous stability and make easier its use for the identification of tumor cells. Microscopic and ultrastructural aspects concerning the related in vitro interactions between ICG-loaded NPs and tumor cell culture were investigated. Obtained results showed an effective stabilization of ICG; furthermore, color inclusions inside the cells treated with ICG-loaded NPs demonstrated the internalization of NPs with associated ICG. Transmission electron microscopy (TEM) analysis demonstrated the cytoplasmic presence of coated vesicles (Ø ≤ 100 nm), hypothesizing their involvement in the mechanism of endocytosis. Therefore, ICG-loaded NPs could be proposed as agents for tumor diagnosis, hypothesizing also in the future a specific therapeutic treatment.
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http://dx.doi.org/10.3390/nano10010133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022782PMC
January 2020

New System Delivering Microwaves Energy for Inducing Subcutaneous Fat Reduction: In - Vivo Histological and Ultrastructural Evidence.

Open Access Maced J Med Sci 2019 Sep 30;7(18):2991-2997. Epub 2019 Aug 30.

Clinic for Psychiatric Disorders "Dr. Laza Lazarevic", Belgrade, Serbia.

Background: Recently, it has been developed a new technology for the reduction of subcutaneous adipose tissue through a non-invasive treatment by microwaves. The main objective of the present study is to demonstrate the feasibility of utilising a non-invasive, localised microwaves (MW) device to induce thermal modifications into subcutaneous adipose tissue only by a controlled electromagnetic field that heats up fat preferentially. This device is provided with a special handpiece appropriately cooled, directly contacting the cutaneous surface of the body, which provides a calibrated energy transfer by microwaves.

Aim: In this paper, microscopic and ultrastructural modifications of subcutaneous adipose tissue induced by microwaves irradiation are evaluated.

Methods: Our experimental plan was designed for collecting biopsy samples, for each skin region treated with a single irradiation session, 1) before treatment (control), 2) immediately after treatment, 3) after 6 hrs, 4) after 1 month, 5) after 2 months. Bioptic samples from each step were processed for light microscopy and transmission electron microscopy. At the same time, each region where biopsies were collected was subjected to ultrasound examination. Recorded images permitted to evaluate the thickness of different layers as epidermis, dermis, hypodermis, connective fasciae, until to muscle layer, and related modifications induced by treatment.

Results: In every biopsy collected at different time-steps, epidermis and superficial dermis appeared not modified compared to control. Differently, already in the short-term biopsies, in the deep dermis and superficial hypodermis, fibrillar connective tissue appeared modified, showing reduction and fragmentation of interlobular collagen septa. The most important adipose tissue modifications were detectable following 1 month from treatment, with a significant reduction of subcutaneous fat, participating both the lysis of many adipocytes and the related phagocytic action of monocytes/macrophages on residuals of compromised structures of adipocytes. In the samples collected two months following treatment, the remnants of adipose tissue appeared normal, and macrophages were completely absent.

Conclusions: Ultrasound, microscopic and ultrastructural evidence are supporting significant effectiveness of the new device treatment in the reduction of subcutaneous fat. In this paper, the possible mechanisms involved in the activation of the monocytes/macrophages system responsible for the removal of adipocytes residuals have also been discussed.
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http://dx.doi.org/10.3889/oamjms.2019.778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910790PMC
September 2019

Staggered Herringbone Microfluid Device for the Manufacturing of Chitosan/TPP Nanoparticles: Systematic Optimization and Preliminary Biological Evaluation.

Int J Mol Sci 2019 Dec 9;20(24). Epub 2019 Dec 9.

Department of Drug Science, University of Pavia, V.le Taramelli 12, 27100 Pavia, Italy.

Chitosan nanoparticles (CS NPs) showed promising results in drug, vaccine and gene delivery for the treatment of various diseases. The considerable attention towards CS was owning to its outstanding biological properties, however, the main challenge in the application of CS NPs was faced during their size-controlled synthesis. Herein, ionic gelation reaction between CS and sodium tripolyphosphate (TPP), a widely used and safe CS cross-linker for biomedical application, was exploited by a microfluidic approach based on a staggered herringbone micromixer (SHM) for the synthesis of TPP cross-linked CS NPs (CS/TPP NPs). Screening design of experiments was applied to systematically evaluate the main process and formulative factors affecting CS/TPP NPs physical properties (mean size and size distribution). Effectiveness of the SHM-assisted manufacturing process was confirmed by the preliminary evaluation of the biological performance of the optimized CS/TPP NPs that were internalized in the cytosol of human mesenchymal stem cells through clathrin-mediated mechanism. Curcumin, selected as a challenging model drug, was successfully loaded into CS/TPP NPs (EE% > 70%) and slowly released up to 48 h via the diffusion mechanism. Finally, the comparison with the conventional bulk mixing method corroborated the efficacy of the microfluidics-assisted method due to the precise control of mixing at microscales.
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http://dx.doi.org/10.3390/ijms20246212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940890PMC
December 2019

IL1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development.

Cancer Immunol Res 2019 06 24;7(6):874-885. Epub 2019 Apr 24.

Humanitas Research Hospital, Rozzano, Italy.

Chronic inflammation, including that driven by autoimmunity, is associated with the development of B-cell lymphomas. IL1R8 is a regulatory receptor belonging to the IL1R family, which negatively regulates NF-κB activation following stimulation of IL1R or Toll-like receptor family members. IL1R8 deficiency is associated with the development of severe autoimmune lupus-like disease in mice. We herein investigated whether concomitant exacerbated inflammation and autoimmunity caused by the deficiency of IL1R8 could recapitulate autoimmunity-associated lymphomagenesis. We thus monitored B-cell lymphoma development during the aging of IL1R8-deficient mice, observing an increased lymphoid cell expansion that evolved to diffuse large B-cell lymphoma (DLBCL). Molecular and gene-expression analyses showed that the NF-κB pathway was constitutively activated in / B splenocytes. In human DLBCL, had reduced expression compared with normal B cells, and higher expression was associated with a better outcome. Thus, silencing is associated with increased lymphoproliferation and transformation in the pathogenesis of B-cell lymphomas associated with autoimmunity.
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http://dx.doi.org/10.1158/2326-6066.CIR-18-0698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176492PMC
June 2019

Poly (ethyl 2-cyanoacrylate) nanoparticles (PECA-NPs) as possible agents in tumor treatment.

Colloids Surf B Biointerfaces 2019 May 19;177:520-528. Epub 2019 Feb 19.

Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy. Electronic address:

Tumor eradication has many challenges due to the difficulty of selectively delivering anticancer drugs to malignant cells avoiding contact with healthy tissues/organs. The improvement of antitumor efficacy and the reduction of systemic side effects can be achieved using drug loaded nanoparticles. In this study, poly (ethyl 2-cyanoacrylate) nanoparticles (PECA-NPs) were prepared using an emulsion polymerization method and their potential for cancer treatment was investigated. The size, polydispersity index and zeta potential of prepared nanoparticles are about 80 nm, 0.08 and -39.7 mV, respectively. The stability test shows that the formulation is stable for 15 days, while an increase in particle size occurs after 30 days. TEM reveals the spherical morphology of nanoparticles; furthermore, FTIR and H NMR analyses confirm the structure of PECA-NPs and the complete polymerization. The nanoparticles demonstrate an in vitro concentration-dependent cytotoxicity against human epithelial colorectal adenocarcinoma cell lines (Caco-2), as assessed by MTT assay. The anticancer activity of PECA-NPs was studied on 3D tumor spheroids models of hepatocellular carcinoma (HepG2) and kidney adenocarcinoma cells (A498) to better understand how the nanoparticles could interact with a complex structure such as a tumor. The results confirm the antitumor activity of PECA-NPs. Therefore, these systems can be considered good candidates in tumor treatment.
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http://dx.doi.org/10.1016/j.colsurfb.2019.02.036DOI Listing
May 2019

Milk microbiome diversity and bacterial group prevalence in a comparison between healthy Holstein Friesian and Rendena cows.

PLoS One 2018 24;13(10):e0205054. Epub 2018 Oct 24.

Institute of Agricultural Biology and Biotechnology, National Research Council (CNR), Lodi, Italy.

Dry and early lactation periods represent the most critical phases for udder health in cattle, especially in highly productive breeds, such as the Holstein Friesian (HF). On the other hand, some autochthonous cattle breeds, such as the Rendena (REN), have a lower prevalence of mastitis and other transition-related diseases. In this study, milk microbiota of 6 HF and 3 REN cows, all raised on the same farm under the same conditions, was compared. A special focus was placed on the transition period to define bacterial groups' prevalence with a plausible effect on mammary gland health. Four time points (dry-off, 1 d, 7-10 d and 30 d after calving) were considered. Through 16S rRNA sequencing, we characterized the microbiota composition for 117 out of the 144 milk samples initially collected, keeping only the healthy quarters, in order to focus on physiological microbiome changes and avoid shifts due to suspected diseases. Microbial populations were very different in the two breeds along all the time points, with REN milk showing a significantly lower microbial biodiversity. The taxonomic profiles of both cosmopolitan and local breeds were dominated by Firmicutes, mostly represented by the Streptococcus genus, although in very different proportions (HF 27.5%, REN 68.6%). Large differences in HF and REN cows were, also, evident from the metabolic predictive analysis from microbiome data. Finally, only HF milk displayed significant changes in the microbial composition along the transition period, while REN maintained a more stable microbiota. In conclusion, in addition to the influence on the final characteristics of dairy products obtained from milk of the two breeds, differences in the milk microbiome might, also, have an impact on their mammary gland health.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205054PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200206PMC
March 2019

Characterization of the blastogenic response to LPS of bovine peripheral blood mononuclear cells.

PLoS One 2018 2;13(10):e0204827. Epub 2018 Oct 2.

University of Tuscia, Department of Agriculture and Forestry Science (DAFNE), Viterbo, Italy.

Mitogens are diverse compounds of plant and microbial origin, widely employed to test immunocompetence in animals. The blastogenic response of bovine Peripheral Blood Mononuclear Cells (PBMC) to lypopolysaccharides (LPS) has been investigated in our laboratories for a long time. In particular, a possible correlation between blastogenic response to LPS and disease resistance of periparturient dairy cows had been observed in previous studies. Most important, low responder cows presented a higher frequency of disease cases after calving, compared with high responder animals. Owing to the above, different aspects of the blastogenic response to LPS were investigated on PBMC of healthy Friesian cows, using a 72-hour Bromodeoxyuridin (BrDU) cell proliferation assay. Stimulation with LPS induced little if any replication of bovine PBMC over 72 hours despite consistent BrDU detection in all the PBMC samples under study. Poor replication of LPS-stimulated PBMC was confirmed by cell cycle and cell growth flow cytometry analyses. In particular, LPS stimulation gave rise to very low percentages of S phase cells, sometimes lower than in control, unstimulated cells, as opposed to Concanavalin A-stimulated PBMC. Magnetic separation and analysis of BrDU-treated bovine PBMC after exposure to LPS showed that both B and CD4 T cells are involved in the blastogenic response to LPS, in contrast with current data based on human and murine models. Finally, LPS caused an early, specific up-regulation of TNF-α and TLR4 genes in bovine PBMC, and significant correlations were shown between the expression of inflammatory cytokine and Indoleamine-pyrrole 2,3-dioxygenase (IDO1) genes. On the whole, our data indicate that differences in the blastogenic response to LPS could be partly accounted for by heterogenicity of responding cells (B and T lymphocytes), which might also have an impact on induction and regulation of inflammatory responses and endotoxin tolerance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204827PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168128PMC
March 2019

Empathy decline at older age?

Aging (Albany NY) 2018 Jun;10(6):1182-1183

Department of Applied Psychology: Health, Development, Enhancement and Intervention, Faculty of Psychology University of Vienna, Vienna, Austria.

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http://dx.doi.org/10.18632/aging.101467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046233PMC
June 2018

Early Regenerative Modifications of Human Postmenopausal Atrophic Vaginal Mucosa Following Fractional CO Laser Treatment.

Open Access Maced J Med Sci 2018 Jan 19;6(1):6-14. Epub 2018 Jan 19.

Universita degli Studi dell'Insubria Dipartimento di Scienze Chirurgiche e Morfologiche, Varese, Italy.

Background: Postmenopausal women experience undesired symptoms that adversely affect their quality of life. In the recent years, a specific 12 - week fractional CO laser treatment has been introduced, with highly significant relief of symptoms.

Aim: The aim of this paper is the identification of the early modifications of structural components of atrophic vaginal mucosa induced by laser irradiation, which is responsible for the restorative processes.

Material And Methods: We investigated by microscopical, ultrastructural and biochemical methods the modifications of the structural components of postmenopausal atrophic vaginal mucosa tissues after 1 hour following a single fractional laser CO application.

Results: In one hour, the mucosal epithelium thickens, with the maturation of epithelial cells and desquamation at the epithelial surface. In the connective tissue, new papillae indenting the epithelium with newly formed vessels penetrating them, new thin fibrils of collagen III are also formed in a renewed turnover of components due to the increase of metalloproteinase - 2. Specific features of fibroblasts support stimulation of their activity responsible of the renewal of the extracellular matrix, with an increase of mechanical support as connective tissue and stimulation of growth and maturation to epithelium thanks to new vessels and related factors delivered.

Conclusion: We found the activation of regenerative mechanisms expressed both in the connective tissue - with the formation of new vessels, new papillae, and new collagen - and in the epithelium with the associated thickening and desquamation of cells at the mucosal surface.
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http://dx.doi.org/10.3889/oamjms.2018.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816317PMC
January 2018

Association of Alpha Tocopherol and Ag Sulfadiazine Chitosan Oleate Nanocarriers in Bioactive Dressings Supporting Platelet Lysate Application to Skin Wounds.

Mar Drugs 2018 Feb 9;16(2). Epub 2018 Feb 9.

Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy.

Chitosan oleate was previously proposed to encapsulate in nanocarriers some poorly soluble molecules aimed to wound therapy, such as the anti-infective silver sulfadiazine, and the antioxidant α tocopherol. Because nanocarriers need a suitable formulation to be administered to wounds, in the present paper, these previously developed nanocarriers were loaded into freeze dried dressings based on chitosan glutamate. These were proposed as bioactive dressings aimed to support the application to wounds of platelet lysate, a hemoderivative rich in growth factors. The dressings were characterized for hydration capacity, morphological aspect, and rheological and mechanical behavior. Although chitosan oleate nanocarriers clearly decreased the mechanical properties of dressings, these remained compatible with handling and application to wounds. Preliminary studies in vitro on fibroblast cell cultures demonstrated good compatibility of platelet lysate with nanocarriers and bioactive dressings. An in vivo study on a murine wound model showed an accelerating wound healing effect for the bioactive dressing and its suitability as support of the platelet lysate application to wounds.
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http://dx.doi.org/10.3390/md16020056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852484PMC
February 2018

Age-related differences in the neural correlates of empathy for pleasant and unpleasant touch in a female sample.

Neurobiol Aging 2018 05 9;65:7-17. Epub 2018 Jan 9.

Department of Applied Psychology: Health, Development, Enhancement and Intervention, Faculty of Psychology, University of Vienna, Vienna, Austria. Electronic address:

Empathy is essential for successful social interactions and relationships. The neural underpinnings of empathy have predominantly been studied in the young adult population, thus little is known about how they evolve across the life span. In the present study, we used functional magnetic resonance imaging to investigate age-related differences in brain activity associated to empathy for positive and negative emotions. Female participants of 3 age groups-adolescents, young, and older adults-underwent an experimental paradigm inducing both first-hand and empathic experience of pleasant and unpleasant touch. Group comparisons and regression analyses revealed that older adults showed lower activation within the anterior insula with respect to young adults, during both empathy conditions. Further analyses provided evidence that years of education, theory of mind ability, gray matter volume, and first-hand affect processing did not account for these effects. These findings indicate that the neural bases of empathy change across different age groups, from adolescence to old age. Different ages and in particular older age seem to significantly influence the way in which we represent and share others' positive and negative emotions.
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http://dx.doi.org/10.1016/j.neurobiolaging.2017.12.028DOI Listing
May 2018

Freeze dried chitosan acetate dressings with glycosaminoglycans and traxenamic acid.

Carbohydr Polym 2018 Mar 28;184:408-417. Epub 2017 Dec 28.

Department of Drug Sciences, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy.

Bleeding control plays an important role to increase survival in the early phase after a traumatic event. The aim of present work was the development of hemostatic sponge-like dressings based on chitosan, in association with glycosaminoglycans (GAG) (chondroitin sulfate or hyaluronic acid) and the improvement of their hemostatic performance by loading tranexamic acid (TA). The dressings were prepared by lyophilizazion and were characterized for mechanical, hydration, bioadhesion properties and morphology. Moreover, FTIR analysis was performed to understand the interactions between the different polyelectrolytes present in the dressings. Clotting was investigated in vitro by using rat whole blood. Moreover, in vitro biocompatibility and proliferation were evaluated towards fibroblasts. Ex vivo proliferation properties were assessed by using human skin. All the dressings were characterised by mechanical, hydration and bioadhesion properties suitable to be applied on bleeding wounds and to absorb bleeding or wound exudate, avoiding tissue dehydration. TA release was fast; TA and chitosan showed a synergic effect to speed up clotting. The dressings were biocompatible and able to sustain cell proliferation in vitro and ex vivo in human skin. In conclusion, sponge-like dressings based on chitosan and GAG and loaded with TA are an effective tool to enhance hemostasis and healing in bleeding wounds.
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http://dx.doi.org/10.1016/j.carbpol.2017.12.066DOI Listing
March 2018

hASC and DFAT, Multipotent Stem Cells for Regenerative Medicine: A Comparison of Their Potential Differentiation In Vitro.

Int J Mol Sci 2017 Dec 13;18(12). Epub 2017 Dec 13.

Centre for Health Technologies, University of Pavia, 27100 Pavia, Italy.

Adipose tissue comprises both adipose and non-adipose cells such as mesenchymal stem cells. These cells show a surface antigenic profile similar to that of bone-marrow-derived MSC. The cells derived from the dedifferentiation of mature adipocytes (DFAT) are another cell population with characteristics of stemness. The aim of this study is to provide evidence of the stemness, proliferation, and differentiation of human adipose stem cells (hASC) and DFAT obtained from human subcutaneous AT and evaluate their potential use in regenerative medicine. Cell populations were studied by histochemical and molecular biology techniques. Both hASC and DFAT were positive for MSC markers. Their proliferative capacity was similar and both populations were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages. DFAT were able to accumulate lipids and their lipoprotein lipase and gene expression were high. Alkaline phosphatase and gene expression were greater in hASC than in DFAT at 14 days but became similar after three weeks. Both cell populations were able to differentiate into chondrocytes, showing positive staining with Alcian Blue and gene expression of and . In conclusion, both hASC and DFAT populations derived from AT have a high differentiation capacity and thus may have applications in regenerative medicine.
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http://dx.doi.org/10.3390/ijms18122699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751300PMC
December 2017
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