Parastoo Memarian  Elham Pishavar  Federica Zanotti  Martina Trentini  Francesca Camponogara  Elisa Soliani  Paolo Gargiulo  Maurizio Isola  Barbara Zavan 《International journal of molecular sciences》2022,23(3)

The successful clinical application of bone tissue engineering requires customized implants based on the receiver’s bone anatomy and defect characteristics. Three-dimensional (3D) printing in small animal orthopedics has recently emerged as a valuable approach in fabricating individualized implants for receiver-specific needs. In veterinary medicine, because of the wide range of dimensions and anatomical variances, receiver-specific diagnosis and therapy are even more critical. The ability to generate 3D anatomical models and customize orthopedic instruments, implants, and scaffolds are advantages of 3D printing in small animal orthopedics. Furthermore, this technology provides veterinary medicine with a powerful tool that improves performance, precision, and cost-effectiveness. Nonetheless, the individualized 3D-printed implants have benefited several complex orthopedic procedures in small animals, including joint replacement surgeries, critical size bone defects, tibial tuberosity advancement, patellar groove replacement, limb-sparing surgeries, and other complex orthopedic procedures. The main purpose of this review is to discuss the application of 3D printing in small animal orthopedics based on already published papers as well as the techniques and materials used to fabricate 3D-printed objects. Finally, the advantages, current limitations, and future directions of 3D printing in small animal orthopedics have been addressed.  相似文献   

    

Jing Yuan Tan  Muhammed Haiqal Low  Yunxin Chen  Francesca Lorraine Wei Inng Lim 《International journal of molecular sciences》2022,23(13)

Chimeric antigen receptor (CAR) T cell therapy has ushered in a new era in cancer treatment. Remarkable outcomes have been demonstrated in patients with previously untreatable relapsed/refractory hematological malignancies. However, optimizing efficacy and reducing the risk of toxicities have posed major challenges, limiting the success of this therapy. The tumor microenvironment (TME) plays an important role in CAR T cell therapy’s effectiveness and the risk of toxicities. Increasing research studies have also identified various biomarkers that can predict its effectiveness and risk of toxicities. In this review, we discuss the various aspects of the TME and biomarkers that have been implicated thus far and discuss the role of creating scoring systems that can aid in further refining clinical applications of CAR T cell therapy and establishing a safe and efficacious personalised medicine for individuals.  相似文献   

    

Domenica Mangraviti  Jessica Maria Abbate  Carmelo Iaria  Francesca Rigano  Luigi Mondello  Marco Quartuccio  Fabio Marino 《International journal of molecular sciences》2022,23(18)

The present work proposes the use of a fast analytical platform for the mass spectrometric (MS) profiling of canine mammary tissues in their native form for the building of a predictive statistical model. The latter could be used as a novel diagnostic tool for the real-time identification of different cellular alterations in order to improve tissue resection during veterinary surgery, as previously validated in human oncology. Specifically, Rapid Evaporative Ionization Mass Spectrometry (REIMS) coupled with surgical electrocautery (intelligent knife—iKnife) was used to collect MS data from histologically processed mammary samples, classified into healthy, hyperplastic/dysplastic, mastitis and tumors. Differences in the lipid composition enabled tissue discrimination with an accuracy greater than 90%. The recognition capability of REIMS was tested on unknown mammary samples, and all of them were correctly identified with a correctness score of 98–100%. Triglyceride identification was increased in healthy mammary tissues, while the abundance of phospholipids was observed in altered tissues, reflecting morpho-functional changes in cell membranes, and oxidized species were also tentatively identified as discriminant features. The obtained lipidomic profiles represented unique fingerprints of the samples, suggesting that the iKnife technique is capable of differentiating mammary tissues following chemical changes in cellular metabolism.  相似文献   

    

Augusta de Santis  Ernesto Scoppola  Maria Francesca Ottaviani  Alexandros Koutsioubas  Lester C. Barnsley  Luigi Paduano  Gerardino D&#x;Errico  Irene Russo Krauss 《International journal of molecular sciences》2022,23(10)

Lipid structural diversity strongly affects biomembrane chemico-physical and structural properties in addition to membrane-associated events. At high concentrations, cholesterol increases membrane order and rigidity, while polyunsaturated lipids are reported to increase disorder and flexibility. How these different tendencies balance in composite bilayers is still controversial. In this study, electron paramagnetic resonance spectroscopy, small angle neutron scattering, and neutron reflectivity were used to investigate the structural properties of cholesterol-containing lipid bilayers in the fluid state with increasing amounts of polyunsaturated omega-3 lipids. Either the hybrid 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine or the symmetric 1,2-docosahexaenoyl-sn-glycero-3-phosphocholine were added to the mixture of the naturally abundant 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine and cholesterol. Our results indicate that the hybrid and the symmetric omega-3 phospholipids affect the microscopic organization of lipid bilayers differently. Cholesterol does not segregate from polyunsaturated phospholipids and, through interactions with them, is able to suppress the formation of non-lamellar structures induced by the symmetric polyunsaturated lipid. However, this order/disorder balance leads to a bilayer whose structural organization cannot be ascribed to either a liquid ordered or to a canonical liquid disordered phase, in that it displays a very loose packing of the intermediate segments of lipid chains.  相似文献   

    

Chiara Trincianti  Vincenzo Meleca  Edoardo La Porta  Maurizio Bruschi  Giovanni Candiano  Andrea Garbarino  Xhuliana Kajana  Alberto Preda  Francesca Lugani  Gian Marco Ghiggeri  Andrea Angeletti  Pasquale Esposito  Enrico Verrina 《International journal of molecular sciences》2022,23(10)

Peritoneal dialysis (PD) represents the dialysis modality of choice for pediatric patients with end-stage kidney disease. Indeed, compared with hemodialysis (HD), it offers many advantages, including more flexibility, reduction of the risk of hospital-acquired infections, preservation of residual kidney function, and a better quality of life. However, despite these positive aspects, PD may be associated with several long-term complications that may impair both patient’s general health and PD adequacy. In this view, chronic inflammation, caused by different factors, has a detrimental impact on the structure and function of the peritoneal membrane, leading to sclerosis and consequent PD failure both in adults and children. Although several studies investigated the complex pathogenic pathways underlying peritoneal membrane alterations, these processes remain still to explore. Understanding these mechanisms may provide novel approaches to improve the clinical outcome of pediatric PD patients through the identification of subjects at high risk of complications and the implementation of personalized interventions. In this review, we discuss the main experimental and clinical experiences exploring the potentiality of the proteomic analysis of peritoneal fluids and extracellular vesicles as a source of novel biomarkers in pediatric peritoneal dialysis.  相似文献   

    

Anna Martina Tedeschi  Fabrizio Di Caprio  Antonella Piozzi  Francesca Pagnanelli  Iolanda Francolini 《International journal of molecular sciences》2022,23(1)

This study combines the use of corn starch and Tetradesmus obliquus microalgae for the production of antioxidant starch films as flexible packaging material. Starch was plasticized with glycerol and blended with 1 w% polyallylamine chosen as an agent to modify the film physical properties. The addition of polyallylamine improved film water stability and water vapor transmission rate as well as mechanical stiffness and tenacity. The dried Tetradesmus obliquus microalgae, which showed an EC₅₀ value of 2.8 mg/mg DPPH (2.2-Diphenyl-1-picrylhydrazyl radical), was then used as antioxidant filler. The addition of microalgae provided the films with good antioxidant activity, which increased with microalgae content increasing. To our knowledge, this is the first study reporting the development of sustainable bioactive packaging films composed of almost 100% starch, and follows the European union’s goals on plastics strategy concerning the promotion of bio-based, compostable plastics and the setting up of approaches to prevent food waste with a simple plastic packaging.  相似文献   

    

Alessandro Marchioni  Roberto Tonelli  Alessandro Andreani  Gaia Francesca Cappiello  Matteo Fermi  Fabiana Trentacosti  Ivana Castaniere  Riccardo Fantini  Luca Tabbì  Dario Andrisani  Filippo Gozzi  Giulia Bruzzi  Linda Manicardi  Antonio Moretti  Serena Baroncini  Anna Valeria Samarelli  Massimo Pinelli  Giorgio De Santis  Alessandro Stefani  Daniele Marchioni  Francesco Mattioli  Enrico Clini 《International journal of molecular sciences》2022,23(5)

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.  相似文献   

    

Andrea Bianconi  Gelsomina Aruta  Francesca Rizzo  Luca Francesco Salvati  Pietro Zeppa  Diego Garbossa  Fabio Cofano 《International journal of molecular sciences》2022,23(8)

Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved.  相似文献   

    

Federico Bolognesi  Nicola Fazio  Filippo Boriani  Viscardo Paolo Fabbri  Davide Gravina  Francesca Alice Pedrini  Nicoletta Zini  Michelina Greco  Michela Paolucci  Maria Carla Re  Sofia Asioli  Maria Pia Foschini  Antonietta D&#x;Errico  Nicola Baldini  Claudio Marchetti 《International journal of molecular sciences》2022,23(3)

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.  相似文献   

    

Bianca Papotti  Maria Pia Adorni  Cinzia Marchi  Francesca Zimetti  Nicoletta Ronda  Giovanni Panighel  Maria Giovanna Lupo  Antonietta Vilella  Daniela Giuliani  Nicola Ferri  Franco Bernini 《International journal of molecular sciences》2022,23(20)

The Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) involvement in Alzheimer’s disease (AD) is poorly investigated. We evaluated the in vitro PCSK9 modulation of astrocyte cholesterol metabolism and neuronal cholesterol supplying, which is fundamental for neuronal functions. Moreover, we investigated PCSK9 neurotoxic effects. In human astrocytoma cells, PCSK9 reduced cholesterol content (−20%; p < 0.05), with a greater effect in presence of beta amyloid peptide (Aβ) (−37%; p < 0.01). PCSK9 increased cholesterol synthesis and reduced the uptake of apoE-HDL-derived cholesterol (−36%; p < 0.0001), as well as the LDL receptor (LDLR) and the apoE receptor 2 (ApoER2) expression (−66% and −31%, respectively; p < 0.01). PCSK9 did not modulate ABCA1- and ABCG1-cholesterol efflux, ABCA1 levels, or membrane cholesterol. Conversely, ABCA1 expression and activity, as well as membrane cholesterol, were reduced by Aβ (p < 0.05). In human neuronal cells, PCSK9 reduced apoE-HDL-derived cholesterol uptake (−41%; p < 0.001) and LDLR/apoER2 expression (p < 0.05). Reduced cholesterol internalization occurred also in PCSK9-overexpressing neurons exposed to an astrocyte-conditioned medium (−39%; p < 0.001). PCSK9 reduced neuronal cholesterol content overall (−29%; p < 0.05) and increased the Aβ-induced neurotoxicity (p < 0.0001). Our data revealed an interfering effect of PCSK9, in cooperation with Aβ, on brain cholesterol metabolism leading to neuronal cholesterol reduction, a potentially deleterious effect. PCSK9 also exerted a neurotoxic effect, and thus represents a potential pharmacological target in AD.  相似文献