Effects of LP-MOCVD prepared TiO2 thin films on the in vitro behavior of gingival fibroblasts

We report on the in vitro response of human gingival fibroblasts (HGF-1 cell line) to various thin films of titanium dioxide (TiO₂) deposited on titanium (Ti) substrates by low pressure metal-organic chemical vapor deposition (LP-MOCVD). The aim was to study the influence of film structural parameters on the cell behavior comparatively with a native-oxide covered titanium specimen, this objective being topical and interesting for materials applications in implantology. HGF-1 cells were cultured on three LP-MOCVD prepared thin films of TiO₂ differentiated by their thickness, roughness, transversal morphology, allotropic composition and wettability, and on a native-oxide covered Ti substrate. Besides traditional tests of cell viability and morphology, the biocompatibility of these materials was evaluated by fibronectin immunostaining, assessment of cell proliferation status and the zymographic evaluation of gelatinolytic activities specific to matrix metalloproteinases secreted by cells grown in contact with studied specimens. The analyzed surfaces proved to influence fibronectin fibril assembly, cell proliferation and capacity to degrade extracellular matrix without considerably affecting cell viability and morphology. The MOCVD of TiO₂ proved effective in positively modifying titanium surface for medical applications. Surface properties playing a crucial role for cell behavior were the wettability and, secondarily, the roughness, HGF-1 cells preferring a moderately rough and wettable TiO₂ coating.     

A restoration framework for ultrasonic tissue characterization

Ultrasonic tissue characterization has become an area of intensive research. This procedure generally relies on the analysis of the unprocessed echo signal. Because the ultrasound echo is degraded by the non-ideal system point spread function, a deconvolution step could be employed to provide an estimate of the tissue response that could then be exploited for a more accurate characterization. In medical ultrasound, deconvolution is commonly used to increase diagnostic reliability of ultrasound images by improving their contrast and resolution. Most successful algorithms address deconvolution in a maximum a posteriori estimation framework; this typically leads to the solution of l(2)-norm or (1)-norm constrained optimization problems, depending on the choice of the prior distribution. Although these techniques are sufficient to obtain relevant image visual quality improvements, the obtained reflectivity estimates are, however, not appropriate for classification purposes. In this context, we introduce in this paper a maximum a posteriori deconvolution framework expressly derived to improve tissue characterization. The algorithm overcomes limitations associated with standard techniques by using a nonstandard prior model for the tissue response. We present an evaluation of the algorithm performance using both computer simulations and tissue-mimicking phantoms. These studies reveal increased accuracy in the characterization of media with different properties. A comparison with state-of-the-art Wiener and l(1)-norm deconvolution techniques attests to the superiority of the proposed algorithm.     

Translational Implications for Radiosensitizing Strategies in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence that includes FP-RMS, harboring the fusion oncoprotein PAX3/7-FOXO1 and FN-RMS, often mutant in the RAS pathway. Risk stratifications of RMS patients determine different prognostic groups and related therapeutic treatment. Current multimodal therapeutic strategies involve surgery, chemotherapy (CHT) and radiotherapy (RT), but despite the deeper knowledge of response mechanisms underpinning CHT treatment and the technological improvements that characterize RT, local failures and recurrence frequently occur. This review sums up the RMS classification and the management of RMS patients, with special attention to RT treatment and possible radiosensitizing strategies for RMS tumors. Indeed, RMS radioresistance is a clinical problem and further studies aimed at dissecting radioresistant molecular mechanisms are needed to identify specific targets to hit, thus improving RT-induced cytotoxicity.     

CD73-Adenosinergic Axis Mediates the Protective Effect of Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Ischemic Renal Damage in a Rat Model of Donation after Circulatory Death

We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system.     

Tolerance,Adaptation, and Cell Response Elicited by Micromonospora sp. Facing Tellurite Toxicity: A Biological and Physical-Chemical Characterization

The intense use of tellurium (Te) in industrial applications, along with the improper disposal of Te-derivatives, is causing their accumulation in the environment, where oxyanion tellurite (TeO₃²⁻) is the most soluble, bioavailable, and toxic Te-species. On the other hand, tellurium is a rare metalloid element whose natural supply will end shortly with possible economic and technological effects. Thus, Te-containing waste represents the source from which Te should be recycled and recovered. Among the explored strategies, the microbial TeO₃²⁻ biotransformation into less toxic Te-species is the most appropriate concerning the circular economy. Actinomycetes are ideal candidates in environmental biotechnology. However, their exploration in TeO₃²⁻ biotransformation is scarce due to limited knowledge regarding oxyanion microbial processing. Here, this gap was filled by investigating the cell tolerance, adaptation, and response to TeO₃²⁻ of a Micromonospora strain isolated from a metal(loid)-rich environment. To this aim, an integrated biological, physical-chemical, and statistical approach combining physiological and biochemical assays with confocal or scanning electron (SEM) microscopy and Fourier-transform infrared spectroscopy in attenuated total reflectance mode (ATR-FTIR) was designed. Micromonospora cells exposed to TeO₃²⁻ under different physiological states revealed a series of striking cell responses, such as cell morphology changes, extracellular polymeric substance production, cell membrane damages and modifications, oxidative stress burst, protein aggregation and phosphorylation, and superoxide dismutase induction. These results highlight this Micromonospora strain as an asset for biotechnological purposes.     

Circulating Small EVs miRNAs as Predictors of Pathological Response to Neo-Adjuvant Therapy in Breast Cancer Patients

Neo-adjuvant therapy (NAT) is increasingly used in the clinic for the treatment of breast cancer (BC). Pathological response to NAT has been associated with improved patients’ survival; however, the current techniques employed for assessing the tumor response have significant limitations. Small EVs (sEVs)-encapsulated miRNAs have emerged as promising new biomarkers for diagnosis and prediction. Therefore, our study aims to explore the predictive value of these miRNAs for the pathological response to NAT in BC. By employing bioinformatic tools, we selected a set of miRNAs and evaluated their expression in plasma sEVs and BC biopsies. Twelve miRNAs were identified in sEVs, of which, miR-21-5p, 221-3p, 146a-5p and 26a-5p were significantly associated with the Miller–Payne (MP) pathological response to NAT. Moreover, miR-21-5p, 146a-5p, 26a-5p and miR-24-3p were independent as predictors of MP response to NAT. However, the expression of these miRNAs showed no correlation between sEVs and tissue samples, indicating that the mechanisms of miRNA sorting into sEVs still needs to be elucidated. Functional analysis of miRNA target genes and drug interactions revealed that candidate miRNAs and their targets, can be regulated by different NAT regimens. This evidence supports their role in governing the patients’ therapy response and highlights their potential use as prediction biomarkers.     

Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!

Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a Drosophila Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.     

Comparison of conventional extraction under reflux conditions and microwave-assisted extraction of oil from popcorn.

Popcorn offers an environmentally friendly alternative to the commercial synthetic loose-fill packing materials. Popcorn could be used for cushioning purposes if the oil is extracted after the popping process. Conventional and microwave-assisted extraction methods were used for oil extraction from whole and ground, popped and unpopped kernels. The conventional extraction method achieved 68.5% oil recovery from whole popped kernels. However, whole unpopped kernels were not efficiently de-oiled with either of the methods. Extraction of oil from popped kernels is recommended; corn varieties with higher starch content and lower oil content should be used.     

Synthesis,characterization and conformational transitions in copolymers of 2‐(o‐chlorophenyl)‐4‐methylene‐1,3‐dioxolane with vinyl monomers

Copolymers of 2‐(o‐chlorophenyl)‐4‐methylene‐1,3‐dioxolane with methyl methacrylate and styrene were synthesized in benzene at 85 °C in the presence of 2,2′‐azobisisobutyronitrile as initiator. The structure of the resulting copolymers was investigated and a polymerization mechanism was proposed. The intrinsic viscosity of the copolymers in dilute solutions of carbon tetrachloride was determined as a function of temperature and conformational transitions were investigated. Copyright © 2004 Society of Chemical Industry