Functional mesoporous poly(ionic liquid)-based copolymer monoliths: From synthesis to catalysis and microporous carbon production

Ionic liquid-functionalized mesoporous polymeric networks with specific surface area up to 935 m²/g have been successfully synthesized one pot by solvothermal copolymerization of divinylbenzene and monomeric ionic liquids. The as-obtained polymers exhibit a monolithic structure featuring large pore volumes, an abundant mesoporosity and an adjustable content of ionic liquids. The effect of the reaction conditions on the pore structure has been studied in detail. These poly(ionic liquid)-based porous networks (PILPNs) have then been employed as precursors in two distinct applications, namely organocatalysis and production of microporous carbon monoliths. Selected organocatalyzed reactions, including carbonatation of propylene oxide by cycloaddition with carbon dioxide, benzoin condensation, and cyanosilylation of benzaldehyde have been readily triggered by PILPNs acting as crosslinked polymer-supported (pre)catalysts. The two latter reactions required the prior deprotonation of the imidazolium salt units with a strong base to successfully generate polymer-supported N-heterocyclic carbenes, referred to as poly(NHC)s. Facile recycling and reuse of polymer-supported (pre)catalysts was achieved by simple filtration owing to the heterogeneous reaction conditions. Furthermore, PILPNs could be easily converted into microporous carbon monoliths via CO₂ activation.     

Cardiovascular,Metabolic and Inflammatory Changes after Ovariectomy and Estradiol Substitution in Hereditary Hypertriglyceridemic Rats

Background: If menopause is really independent risk factor for cardiovascular disease is still under debate. We studied if ovariectomy in the model of insulin resistance causes cardiovascular changes, to what extent are these changes reversible by estradiol substitution and if they are accompanied by changes in other organs and tissues. Methods: Hereditary hypertriglyceridemic female rats were divided into three groups: ovariectomized at 8th week (n = 6), ovariectomized with 17-β estradiol substitution (n = 6), and the sham group (n = 5). The strain of abdominal aorta measured by ultrasound, expression of vascular genes, weight and content of myocardium and also non-cardiac parameters were analyzed. Results: After ovariectomy, the strain of abdominal aorta, expression of nitric oxide synthase in abdominal aorta, relative weight of myocardium and of the left ventricle and circulating interleukin-6 decreased; these changes were reversed by estradiol substitution. Interestingly, the content of triglycerides in myocardium did not change after ovariectomy, but significantly increased after estradiol substitution while adiposity index did not change after ovariectomy, but significantly decreased after estradiol substitution. Conclusion: Vascular and cardiac parameters under study differed in their response to ovariectomy and estradiol substitution. This indicates different effects of ovariectomy and estradiol on different cardiovascular but also extracardiac structures.     

In Vivo Evaluation of Sgc8-c Aptamer as a Molecular Imaging Probe for Colon Cancer in a Mouse Xenograft Model

Recent biotechnological applications in the field of clinical oncology led to the identification of new biomarkers as molecular targets of cancer, and to broad developments in the field of personalized medicine. Aptamers are oligonucleotides (ssDNA or RNA) that are selected to specifically recognize a molecular target with high affinity and specificity. Based on this, new horizons for their use as molecular imaging probes are being explored. The objective of this work was to evaluate the Sgc8-c aptamer conjugated with Alexa Fluor 647 fluorophore as an imaging probe in a colon tumor xenograft mouse model, with potential application in molecular imaging. In this study, the LS174T cell line was used to induce colorectal adenocarcinoma in nude mice. After confirmation of PTK7 overexpression by immunohistochemistry, in vivo studies were performed. Pharmacokinetic, in vivo and ex vivo biodistribution imaging, and a competition assay were evaluated by fluorescence imaging. In vivo visualization of the probe in the tumors was assessed two hours after aptamer probe administration, exhibiting excellent tumor-to-background ratios in biodistribution studies and high specificity in the competition test. Our results demonstrated the functionality of Scg8-c as an imaging probe for colon cancer, with potential clinical applications.     

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization,Biomechanical and Biocompatibility Characterization Using New Approaches

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.     

CD8+ T Cell Senescence: Lights and Shadows in Viral Infections,Autoimmune Disorders and Cancer

CD8⁺ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8⁺ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8⁺ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.     

Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation

There is accumulating evidence that platelets play roles beyond their traditional functions in thrombosis and hemostasis, e.g., in inflammatory processes, infection and cancer, and that they interact, stimulate and regulate cells of the innate immune system such as neutrophils, monocytes and macrophages. In this review, we will focus on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. We take a closer look at the contributions of major platelet receptors GPIb, α_IIbβ₃, TLT-1, CLEC-2 and Toll-like receptors (TLRs) as well as secretions from platelet granules on platelet–neutrophil aggregate and neutrophil extracellular trap (NET) formation in atherosclerosis, transfusion-related acute lung injury (TRALI) and COVID-19. Further, we will address platelet–monocyte and macrophage interactions during cancer metastasis, infection, sepsis and platelet clearance.     

Targeting the DNA Damage Response to Increase Anthracycline-Based Chemotherapy Cytotoxicity in T-Cell Lymphoma

Mature T-cell lymphomas (MTCLs) represent a heterogeneous group of aggressive non-Hodgkin lymphomas comprising different entities. Anthracycline-based regimens are considered the standard of care in the front-line treatment. However, responses to these approaches have been neither adequate nor durable, and new treatment strategies are urgently needed to improve survival. Genomic instability is a common feature of cancer cells and can be caused by aberrations in the DNA damage response (DDR) and DNA repair mechanisms. Consistently, molecules involved in DDR are being targeted to successfully sensitize cancer cells to chemotherapy. Recent studies showed that some hematological malignancies display constitutive DNA damage and intrinsic DDR activation, but these features have not been investigated yet in MTCLs. In this study, we employed a panel of malignant T cell lines, and we report for the first time the characterization of intrinsic DNA damage and basal DDR activation in preclinical models in T-cell lymphoma. Moreover, we report the efficacy of targeting the apical kinase ATM using the inhibitor AZD0156, in combination with standard chemotherapy to promote apoptotic cell death. These findings suggest that DDR is an attractive pathway to be pharmacologically targeted when developing novel therapies and improving MTCL patients’ outcomes.     

Sustainable Bioactive Packaging Based on Thermoplastic Starch and Microalgae

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.     

Active Materials for 3D Printing in Small Animals: Current Modalities and Future Directions for Orthopedic Applications

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.