Cellular Topological Packings in Early Embryos

At very early embryonic stages, when embryos are composed of just a few cells, establishing the correct packing arrangements (contacts) between cells is essential for proper development of the organism. As early as the 4-cell stage, the observed blastomere packings in different species are different and, in many cases, differ from the equilibrium packings expected for simple adherent and deformable particles.We use a novel 3D Voronoi-augnemted Langevin simulator to systematically study how the forces between blastomeres, their division rates, orientation of cell division, and embryonic confinement influence the final packing configurations. In the absence of physical confinement of the embryo, we find that blastomere packings are not robust, with multiple packing configurations simultaneously possible (degeneracy) and are very sensitive to parameter changes. Our results indicate that the geometry of the embryonic confining shell determines the packing configurations at the 4-cell stage, removing degeneracy in the possible packing configurations and overriding division rules in most cases.Furthermore, we use our simulator to study the robustness of the C. elegans early embryo to noise in division timing and angle. We find that there exists a range of timing and angular noise that the embryo is fully robust to and categorize the errors outside this regime as coming from mistimed divisions or misplaced cells. We also study how robust the embryo is to overall shifts in the timing offset between the AB and P1 divisions and find that even large changes can be non-lethal. Finally, we systematically investigate how robust the embryo is to deterministic shifts in division directions from the wildtype rules and find that the major source of lethal error is from offsets of more than 90 degrees to the P2-EMS division axis. Overall, our results demonstrate how confinement, division timing and division rules all contribute to ensuring robust development with confinement setting the overall packing topology and division timings and rules specifying where individual cells will go within that shape

Polymer-based systems for controlled release and targeting of drugs

The current need to find new advanced approaches to carry biologically active substances (conventional organic drugs, peptides, proteins (such as antibodies), and nucleic acid-based drugs (NABDs such as siRNA and miRNA)) in the body fluids, to realize targeted therapies and even personalized ones, goes hand in hand with research on the performance of new materials to better realize appropriate drug vectors [...]

Inulin for Cancer Therapy: Present and Perspectives

Inulin is an extremely adaptable polysaccharides consisting of glucopyranose end-capped (\u3b2-1,2) fructose repeating units and, as it is, can be classified as an inherently multifunctional polymeric scaffold. It may be further functionalized employing mild conditions to give rise desired biological and physicochemical properties exploitable for targeted anticancer applications (e.g., active targeting toward specific cytotypes, self-assembling behavior, selective cytoxicity and hyperthermia features). In this review, the main chemical features and the inulin derivatives applications in the field of targeted anticancer therapy is reported and discusse

Photocrosslinkable polyaspartamide/polylactide copolymer and its porous scaffolds for chondrocytes

With the aim to produce, by a simple and reproducible technique, porous scaffolds potentially employable for tissue engineering purposes, in this work, we have synthesized a methacrylate (MA) copolymer of \u3b1,\u3b2-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) and polylactic acid (PLA). PHEA-PLA-MA has been dissolved in organic solvent at different concentrations in the presence of NaCl particles with different granulometry, and through UV irradiation and further salt leaching technique, various porous scaffolds have been prepared. Obtained samples have been characterized by scanning electron microscopy and their porosity has been evaluated as well as their degradation profile in aqueous medium in the absence or in the presence of esterase from porcine liver. PHEA-PLA-MA scaffold that has shown homogeneous porosity and the best degradation profile has been further characterized to study its mechanical properties along with its capacity to incorporate and to control the release of dexamethasone. Finally, the ability to allow a three-dimensional culture of bovine articular chondrocytes have been also investigate

Folic acid-functionalized graphene oxide nanosheets via plasma etching as a platform to combine NIR anticancer phototherapy and targeted drug delivery

PEGylated graphene oxide (GO) has shown potential as NIR converting agent to produce local heat useful in breast cancer therapy, since its suitable photothermal conversion, high stability in physiological fluids, biocompatibility and huge specific surface. GO is an appealing nanomaterial for potential clinical applications combining drug delivery and photothermal therapy in a single nano-device capable of specifically targeting breast cancer cells. However, native GO sheets have large dimensions (0.5-5 mu m) such that tumor accumulation after a systemic administration is usually precluded. Herein, we report a step-by-step synthesis of folic acid-functionalized PEGylated GO, henceforth named GO-PEG-Fol, with small size and narrow size distribution (similar to 30 +/- 5 nm), and the ability of efficiently converting NIR light into heat. GO-PEG-Fol consists of a nano-GO sheet, obtained by fragmentation of GO by means of non-equilibrium plasma etching, fully functionalized with folic acid-terminated PEG(2000) chains through amidic coupling and azide-alkyne click cycloaddition, which we showed as active targeting agents to selectively recognize breast cancer cells such as MCF7 and MDA-MB-231. The GO-PEG-Fol incorporated a high amount of doxorubicin hydrochloride (Doxo) (> 33%) and behaves as NIR-light-activated heater capable of triggering sudden Doxo delivery inside cancer cells and localized hyperthermia, thus provoking efficient breast cancer death. The cytotoxic effect was found to be selective for breast cancer cells, being the IC50 up to 12 times lower than that observed for healthy fibroblasts. This work established plasma etching as a cost-effective strategy to get functionalized nano-GO with a smart combination of properties such as small size, good photothermal efficiency and targeted cytotoxic effect, which make it a promising candidate as photothermal agent for the treatment of breast cancer

Near-Infrared, Light-Triggered, On-Demand Antiinflammatories and Antibiotics Release by Graphene Oxide/Elecrospun PCL Patch for Wound Healing

Very recently, significant attention has been focused on the adsorption and cell adhesion properties of graphene oxide (GO), because it is expected to allow high drug loading and controlled drug release, as well as the promotion of cell adhesion and proliferation. This is particularly interesting in the promotion of wound healing, where antibiotics and anti-inflammatories should be locally released for a prolonged time to allow fibroblast proliferation. Here, we designed an implantable patch consisting of poly(caprolactone) electrospun covered with GO, henceforth named GO–PCL, endowed with high ibuprofen (5.85 mg cm−2), ketoprofen (0.86 mg cm−2), and vancomycin (0.95 mg cm−2) loading, used as anti-inflammatory and antibiotic models respectively, and capable of responding to near infrared (NIR)-light stimuli in order to promptly release the payload ondemand beyond three days. Furthermore, we demonstrated the GO is able to promote fibroblast adhesion, a key characteristic to potentially provide wound healing in vivo

Transport and Spectroscopic Studies of the Effects of Fullerene Structure on the Efficiency and Lifetime of Polythiophene-based Solar Cells

Time-dependent measurements of both power conversion efficiency and ultraviolet-visible absorption spectroscopy have been observed for solar cell blends containing the polymer poly(3-hexylthiophene-2,5-diyl) (P3HT) with two different functionalized C60 electron acceptor molecules: commercially available [6,6]-phenyl C61 butyric acid methyl ester (PCBM) or [6,6]-phenyl C61 butyric acid octadecyl ester (PCBOD) produced in this laboratory. Efficiency was found to decay with an exponential time dependence, while spectroscopic features show saturating exponential behavior. Time constants extracted from both types of measurements showed reasonable agreement for samples produced from the same blend. In comparison to the PCBM samples, the stability of the PCBOD blends was significantly enhanced, while both absorption and power conversion efficiency were decreased.Comment: manuscript submitted to Solar Energy Materials and Solar Cell

Magnetic resonance imaging in cervical spinal cord compression

In patients with cervical spondylotic myelopathy MRI sometimes shows increased signal intensity zones on the T2-weighted images. It has been suggested that these findings carry prognostic significance. We studied 56 subjects with cervical spinal cord compression. Twelve patients showed an increased signal intensity (21.4%) and a prevalence of narrowing of the AP-diameter (62% vs 24%). Furthemore, in this group, there was evidence of a longer mean duration of the symptoms and, in most of the patients, of more serious clinical conditions. The importance of these predisposing factors remains, however, to be clarified since they are also present in some patients without the increased signal intensity

Adipose stem cells on the basis of tumor transformation

Mesenchymal stem cells thanks to their differentiated multipotent ability are considered the most promising candidate for tissue engineering and regenerative medicine. The source of mesenchymal stem cells up to about 20 years was represented by the bone marrow, but due to their limited amount of cells together with a very invasive and painfull surgical treatment, poorly accepted by patients, has led the scientific community to investigate an alternative mesenchymal stem cells source with similar properties. In particular, the adipose tissue has attracted the greatest interest thanks to its relative abundance, the easy of availability and the large amounts of mesenchymal stem cells which are obtenible. So this adipose stem cells subpopulation, once verified the same differentiation potential of them derived from bone marrow, represent the ideal type of adult mesenchymal stem cells useful for numerous regenerative and tissue engineering applications. In particular the bone regeneration, obtained after the lipotransfer of a specific stem cells subpopulation isolated from adipose tissue, should be considered one of the most successful applications in the field of regenerative medicine and tissue engineering. (Chapter 1). A further widespread use of mesenchymal stem cells is to reconstructive medicine. In particular, most patients with breast cancer, whenever possible, based on the type and stage cancer disease (Chapter 2), first make use of a demolitive surgery, in order to completely remove the tumor mass presence, and then resort to a reconstructive plastic surgery procedure. In breast cancer patients it is often used the adipose tissue as autologous filler. Even though the surgical treatment does not represent a potential danger for the patient, many scientific works have highlighted how the use of these self transplantations constitute a great risk for a possible cancer relapse despite the absence of a minimal residual disease. The presence of a mature adipocytes population infact, is responsible of a specific microenvironment, composed by pro-inflammatory cytokines and paracrine signals, that induce a generalized inflammatory state and which stimulate a proliferative return of those few quiescent cancer cells that still remain in the implantation site. In particular we have seen that the action of adipokines and interleukins generated by adipose autologous filler works both on differentiated tumor cells, just in a active proliferation cell phase but also on the cancer stem cell population that instead reside in a quiescent cell cycle phase. (Chapter 3). Therefore it is essential develop a more accurate and specific lipofilling procedure, especially going to select an appropriate autologous filler, in which a particular adipose stem cell subpopulation, with great regenerating properties has to be chosen among the adipose populations already present in conventional fillers. (Chapters 4). So the goal of this study is to enable the development of new selective therapies useful to remove the cancer stem cells, real responsible for tumor relapse. One of the most promising cancer therapies among those currently in the testing phase could be the differentiative therapy, and specifically one that uses the negative regulatory properties of the miRNAs (Chapter 5)

Variations in the lipid profile of patients with chronic renal failure treated with pyridoxine

BACKGROUND: Hyperhomocysteinemia and lipid abnormalities are commonly found in patients with chronic renal failure; both are recognized as risk factors for atherosclerosis. The homocysteine-lowering effect of pyridoxine is controversial. This study was performed to determine the effect of a high dose of pyridoxine (300 mg i.v. three times a week) on plasma and red blood cell lipid profile and plasma homocysteine concentration in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (basal 1), after 30 and 60 days of treatment and 4 months after withdrawal (basal 2). RESULTS: Pyridoxine supplementation induced a significant decrease in total plasma homocysteine level and also a lowering effect in plasma total cholesterol and triglycerides. These biochemical data increased when the samples were taken at basal 2, reaching the levels obtained at the beginning of the experiment. LDL cholesterol increased whereas HDL cholesterol was reduced during the treatment. In erythrocyte membranes vitamin B6 therapy enhanced the cholesterol/phospholipid ratio as well as the fluorescence anisotropy of diphenyl-hexatriene. CONCLUSIONS: We conclude that high doses of pyridoxine represent an effective strategy to ameliorate both plasma homocysteine levels and lipid profiles in chronic renal failure patients, protecting them from atherosclerosis. Further research using a long-term treatment would be necessary in an attempt to restore the fatty acid pattern and the fluidity of red cell membranes