Innovative Biomaterials for Tissue Engineering

In the field of regenerative medicine, biomaterials play a crucial role since they may serve as a support (scaffold) to promote cell growth and differentiation in order to promote the healing of tissue lesion. The aim of this chapter will be to analyze the properties of more recent biomaterials suitable for tissue engineering strategies, to end to define better and innovative materials for scaffold production. To this purpose, we will analyze the main materials (natural and synthetic) and their characteristics, such as biocompatibility, bioactivity, and biodegradation, and it will be discussed how their chemical-physical properties (surface morphology, porosity, stiffness, and mechanical strength) could affect the interaction with cells and living system. Moreover, the chapter will be focused on methods of extraction or production of biomaterial suitable for scaffolds

Genomic profiling of cortical neurons following exposure to β-amyloid

In vitro and in vivo studies have shown that beta-amyloid peptide induces neuronal cell death. To explore the molecular basis underlying beta-amyloid-induced toxicity, we analyzed gene expression profiles of cultured rat cortical neurons treated for 24 and 48 h with synthetic beta-amyloid peptide. From the 8740 genes interrogated by oligonucleotide microarray analysis, 241 genes were found to be differentially expressed and segregated into distinct clusters. Functional clustering based on gene ontologies showed coordinated expression of genes with common biological functions and metabolic pathways. The comparison with genes differentially expressed in cerebellar granule neurons following serum and potassium deprivation indicates the existence of common regulatory mechanisms underlying neuronal cell death. Our results offer a genomic view of the changes that accompany beta-amyloid-induced neurodegeneration

Delayed luminescence to monitor programmed cell death induced by berberine on thyroid cancer cells

Correlation between apoptosis and UVA-induced ultraweak photon emission delayed luminescence (DL) from tumor thyroid cell lines was investigated. In particular, the effects of berberine, an alkaloid that has been reported to have anticancer activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell lines, as representative of follicular and anaplastic thyroid human cancer, respectively, were chosen. The results show that berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since berberine acts especially at the mitochondrial level. The decrease of DL blue component for both cell lines could be related to the decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a hallmark of induced apoptosis. In contrast, the response in the red spectral range is different for the two cell lines and may be ascribed to a different iron homeostasis

N-cadherin has a protective role in stable human atherosclerotic plaques: a morphological and immunohistochemical study

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Conditioned Media From Glial Cells Promote a Neural-Like Connexin Expression in Human Adipose-Derived Mesenchymal Stem Cells

The expression of neuronal and glial connexins (Cxs) has been evaluated in adipose-derived mesenchymal stem cells (ASCs) whose neural differentiation was promoted by a conditioned medium (CM) obtained from cultures of olfactory ensheathing cells (OECs) or Schwann cells (SCs). By immunocytochemistry and flow cytometer analysis it was found that Cx43 was already considerably expressed in naïve ASCs and further increased after 24 h and 7 days from CM exposition. Cx32 and Cx36 were significantly improved in conditioned cultures compared to control ASCs, whereas a decreased expression was noticed in the absence of CM treatments. Cx47 was virtually absent in any conditions. Altogether, high basal levels and induced increases of Cx43 expression suggest a potential attitude of ASCs toward an astrocyte differentiation, whereas the lack of Cx47 would indicate a poor propensity of ASCs to become oligodendrocytes. CM-evoked Cx32 and Cx36 increases showed that a neuronal- or a SC-like differentiation can be promoted by using this strategy. Results further confirm that environmental cues can favor an ASC neural differentiation, either as neuronal or glial elements. Of note, the use of glial products present in CM rather than the addition of chemical agents to achieve such differentiation would resemble “more physiological” conditions of differentiation. As a conclusion, the overexpression of typical neural Cxs would indicate the potential capability of neural-like ASCs to interact with neighboring neural cells and microenvironment

po 053 the phospholipase ddhd1 as a new target in colorectal cancer therapy

Introduction We have recently demonstrated that Citrus-limon derived nanovesicles are able to decrease colon cancer cell viability and that this effect is associated with the down-regulation of the intracellular phospholipase DDHD domain-containing protein 1 (DDHD1). While few studies are currently available on DDHD1 contribution in neurological disorders, information on its involvement in cancer is missing. Here we investigate the role of DDHD1 in colon cancer. Material and methods DDHD1 siRNAs and overexpression vector were transfected into colorectal cancer and normal cells to down-regulate or up-regulate DDHD1 expression. In vitro and in vivo assays were performed to investigate the functional role of DDHD1 in colorectal cancer cell growth. Quantitative proteomics by SWATH-MS was performed to determinate the molecular effects induced by DDHD1 silencing in colorectal cancer cells. Results and discussions Our evidences indicate that DDHD1 supports colon cancer cell proliferation and survival, since its down-regulation reduces in vitro colon cancer cell viability and increases apoptosis rate, without affecting normal cells. On the contrary, in vivo studies demonstrate that the xenograft tumours, derived from DDHD1-overexpressing cells, have a higher proliferation rate compared to control animals. Finally, a proteomic analysis of silenced cells opens up to the opportunity to define the molecular effects of DDHD1 silencing: we found that functional categories, significantly affected by DDHD1 silencing, was specifically related to cancer phenotype and for the first time associated to DDHD1 activity. Conclusion In summary, here we provide the first evidence of DDHD1 role in cancer, pointing out the possibility to define a new target to design more effective therapies for colon cancer patients. In addition, the proteomic analysis allows us to add new knowledge of DDHD1 cytoplasmic activity, highlighting its involvement in both known and previously unrecognised intracellular pathways and identifying multiple mechanisms that may explain the suppressed cancer cell growth induced by DDHD1 silencing

Anaplastic Thyroid Carcinoma: Current Treatments and Potential New Therapeutic Options with Emphasis on TfR1/CD71

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers. Actually, ATC is refractory to conventional therapies, including surgery, chemotherapy, radiotherapy, and radioiodine (131I) therapy. Accordingly, genetic and molecular characterizations of ATC have been frequently and periodically reviewed in order to identify potential biological markers exploitable for target therapy. This review briefly focuses on main molecular events that characterize ATC and provides an update about preclinical studies. In addition, the overexpression of transferrin receptor 1 (TfR1/CD71) by neoplastic cells of ATC is emphasized in that it could represent a potential therapeutic target. In this regard, new therapeutic approaches based on the use of monoclonal or recombinant antibodies, or transferrin-gallium-TfR1/CD71 molecular complexes, or lastly small interfering RNAs (siRNAs) are proposed

Involvement of the Heme-Oxygenase Pathway in the Antiallodynic and Antihyperalgesic Activity of Harpagophytum procumbens in Rats

Harpagophytum procumbens (H. procumbens), also known as Devil’s Claw, has been used to treat a wide range of pathological conditions, including pain, arthritis and inflammation. Inflammatory mediators, released at the site of injury, can sensitize nociceptive terminals and are responsible for allodynia and hyperalgesia. Carbon monoxide (CO), produced in a reaction catalyzed by the enzyme heme oxygenase (HO), may play a role in nociceptive processing and has also been recognized to act as a neurotransmitter or neuromodulator in the nervous system. This study was designed to investigate whether the HO/CO pathway is involved in the analgesic response of H. procumbens in carrageenan-induced hyperalgesia in rats. Mechanical allodynia and thermal hyperalgesia were evaluated by using von Frey filaments and the plantar test, respectively. The results of our experiments showed that pretreatment with the HO inhibitor ZnPP IX significantly decreased the antihyperalgesic effect produced by H. procumbens (800 mg/kg, i.p.) in carrageenan-injected rats. Consistently, the pretreatment with hemin, a HO-1 substrate, or CORM-3, a CO releasing molecule, before a low dose of H. procumbens (300 mg/kg, i.p.) induced a clear antiallodynic response in carrageenan injected rats. These results suggest the involvement of HO-1/CO system in the antiallodynic and antihyperalgesic effect of H. procumbens in carrageenan-induced inflammatory pain

An Advanced, Silicon-Based Substrate for Sensitive Nucleic Acids Detection

Surface substrate and chemical functionalization are crucial aspects for the fabrication of the sensitive biosensor based on microarray technology. In this paper, an advanced, silicon-based substrate (A-MA) allowing enhancement of optical signal for microarray application is described. The substrate consists in a multilayer of Si/Al/SiO2 layers. The optical signal enhancement is reached by a combination of the mirror effect of Al film and the SiO2 thickness around 830 nm, which is able to reach the maximum of interference for the emission wavelength of the Cy5 fluorescent label. Moreover, SiO2 layer is suitable for the immobilization of single-strand DNA through standard silane chemistry, and probe densities of about 2000 F/um2 are reached. The microarray is investigated in the detection of HBV (Hepatitis B Virus) pathogen with analytical samples, resulting in a dynamic linear range of 0.05–0.5 nM, a sensitivity of about 18000 a.u. nM−1, and a Limit of Detection in the range of 0.031–0.043 Nm as a function of the capture probe sequence