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Background/Aim: Nanomedicine is a promising scientific field that exploits the unique properties of innovative nanomaterials, providing alternative solutions in diagnostics, prevention and therapeutics. Titanium dioxide nanoparticles (TiO2NPs) have a great spectrum of photocatalytic antibacterial and anticancer applications. The chemical modification of TiO2optimizes its bioactive performance. The aim of this study was the development of silver modified NPs (Ag/TiO2NPs) with anticancer potential. Materials and Methods: Ag/TiO2NPs were prepared through the sol-gel method, were fully characterized and were tested on cultured breast cancer epithelial cells (MCF-7 and MDAMB-231). The MTT colorimetric assay was used to estimate cellular viability. Western blot analysis of protein expression along with a DNA-laddering assay were employed for apoptosis detection. Results and Conclusion: We show that photo-activated Ag/TiO2NPs exhibited significant cytotoxicity on the highly malignant MDA-MB-231 cancer cells, inducing apoptosis, while MCF-7 cells that are characterized by low invasive properties were unaffected under the same conditions. © 2021 International Institute of Anticancer Research. All rights reserved.

One of the prevailing perceptions regarding the ageing of cells and organisms is the intracellular gradual accumulation of oxidatively damaged macromolecules, leading to the decline of cell and organ function (free radical theory of ageing). This chemically undefined material known as “lipofuscin,” “ceroid,” or “age pigment” is mainly formed through unregulated and nonspecific oxidative modifications of cellular macromolecules that are induced by highly reactive free radicals. A necessary precondition for reactive free radical generation and lipofuscin formation is the intracellular availability of ferrous iron (Fe2+) (“labile iron”), catalyzing the conversion of weak oxidants such as peroxides, to extremely reactive ones like hydroxyl (HO• ) or alcoxyl (RO• ) radicals. If the oxidized materials remain unrepaired for extended periods of time, they can be further oxidized to generate ultimate over-oxidized products that are unable to be repaired, degraded, or exocytosed by the relevant cellular systems. Additionally, over-oxidized materials might inactivate cellular protection and repair mechanisms, thus allowing for futile cycles of increasingly rapid lipofuscin accumulation. In this review paper, we present evidence that the modulation of the labile iron pool distribution by nutritional or pharmacological means represents a hitherto unappreciated target for hampering lipofuscin accumulation and cellular ageing. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Cockayne syndrome (CS) is a DNA repair syndrome characterized by a broad spectrum of clinical manifestations such as neurodegeneration, premature aging, developmental impairment, photosensitivity and other symptoms. Mutations in Cockayne syndrome protein B (CSB) are present in the vast majority of CS patients and in other DNA repair-related pathologies. In the literature, the role of CSB in different DNA repair pathways has been highlighted, however, new CSB functions have been identified in DNA transcription, mitochondrial biology, telomere maintenance and p53 regulation. Herein, we present an overview of identified structural elements and processes that impact on CSB activity and its post-translational modifications, known to balance the different roles of the protein not only during normal conditions but most importantly in stress situations. Moreover, since CSB has been found to be overexpressed in a number of different tumors, its role in cancer is presented and possible therapeutic targeting is discussed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

P14ARF (ARF; Alternative Reading Frame) is an extensively characterized tumor suppressor which, in response to oncogenic stimuli, mediates cell cycle arrest and apoptosis via p53-dependent and independent routes. ARF has been shown to be frequently lost through CpG island promoter methylation in a wide spectrum of human malignancies, such as colorectal, prostate, breast, and gastric cancers, while point mutations and deletions in the p14ARF locus have been linked with various forms of melanomas and glioblastomas. Although ARF has been mostly studied in the context of tumorigenesis, it has been also implicated in purely developmental processes, such as spermatogenesis, and mammary gland and ocular development, while it has been additionally involved in the regulation of angiogenesis. Moreover, ARF has been found to hold important roles in stem cell self-renewal and differentiation. As is often the case with tumor suppressors, ARF functions as a pleiotropic protein regulating a number of different mechanisms at the crossroad of development and tumorigenesis. Here, we provide an overview of the non-canonical functions of ARF in cancer and developmental biology, by dissecting the crosstalk of ARF signaling with key oncogenic and developmental pathways. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Humoral immunity has emerged as a vital immune component against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, a subset of recovered Coronavirus Disease-2019 (COVID-19) paucisymptomatic/asymptomatic individuals do not generate an antibody response, constituting a paradox. We assumed that immunodiagnostic assays may operate under a competitive format within the context of antigenemia, potentially explaining this phenomenon. We present a case where persistent antigenemia/viremia was documented for at least 73 days post-symptom onset using ‘in-house’ methodology, and as it progressively declined, seroconversion took place late, around day 55, supporting our hypothesis. Thus, prolonged SARS-CoV-2 anti-genemia/viremia could mask humoral responses, rendering, in certain cases, the phenomenon of ‘non-responders’ a misnomer. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

The worldwide COVID-19 pandemic outburst has caused a serious public health issue with increasing needs of accurate and rapid diagnostic and screening testing. This situation requires an optimized management of the chemical reagents, the consumables, and the human resources, in order to respond accurately and effectively, controlling the spread of the disease. Testing on pooled samples maximizes the number of tested samples, by minimizing the time and the lab supplies needed. The general conceptualization of the pooling method is based on mixing samples together in a batch. Individual testing is needed only if a specific pool exhibits a positive result. The development of alternative hybrid methods, based on “in house” protocols, utilizing commercially available consumables, in combination with a reliable pooling method would provide a solution, focusing on the better exploitation of the personnel and the lab supplies, allowing for rapid screening of a population in a reasonably short time. © 2020 Elsevier B.V.

The multivariate condition of cancer disease has been approached in various ways, by the scientific community. Recent studies focus on individualized treatments, minimizing the undesirable consequences of the conventional methods, but the development of an alternative effective therapeutic scheme remains to be held. Nanomedicine could provide a solution, filling this gap, exploiting the unique properties of innovative nanostructured materials. Nanostructured titanium dioxide (TiO2) has a variety of applications of daily routine and of advanced technology. Due to its biocompatibility, it has also a great number of biomedical applications. It is now clear that photo-excited TiO2 nanoparticles, induce generation of pairs of electrons and holes which react with water and oxygen to yield reactive oxygen species (ROS) that have been proven to damage cancer cells, triggering controlled cellular processes. The aim of this review is to provide insights into the field of nanomedicine and particularly into the wide context of TiO2-NP-mediated anticancer effect, shedding light on the achievements of nanotechnology and proposing this nanostructured material as a promising anticancer photosensitizer. © 2020 The Author(s)

The combined effects of ionizing radiation (IR) with high-z metallic nanoparticles (NPs) such as gold has developed a growing interest over the recent years. It is currently accepted that radiosensitization is not only attributed to physical effects but also to underlying chemical and biological mechanisms’ contributions. Low-and high-linear energy transfer (LET) IRs produce DNA damage of different structural types. The combination of IR with gold nanoparticles may increase the clustering of energy deposition events in the vicinity of the NPs due to the production mainly of photoelectrons and Auger electrons. Biological lesions of such origin for example on DNA are more difficult to be repaired compared to isolated lesions and can augment IR’s detrimental effects as shown by numerous studies. Transmission electron microscopy (TEM) offers a unique opportunity to study the complexity of these effects on a very detailed cellular level, in terms of structure, including nanoparticle uptake and damage. Cellular uptake and nanoparticle distribution inside the cell are crucial in order to contribute to an optimal dose enhancement effect. TEM is mostly used to observe the cellular localization of nanoparticles. However, it can also provide valuable insights on the NPs’ radiosensitization pathways, by studying the biochemical mechanisms through immunogold-labelling of antigenic sites at ultrastructural level under high resolution and magnification. Here, our goal is to describe the possibilities, methodologies and proper use of TEM in the interest of studying NPs-based radiosensitization mechanisms. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

The genome is exposed daily to many deleterious factors. Ubiquitination is a mechanism that regulates several crucial cellular functions, allowing cells to react upon various stimuli in order to preserve their homeostasis. Ubiquitin ligases act as specific regulators and actively participate among others in the DNA damage response (DDR) network. UBE4B is a newly identified member of E3 ubiquitin ligases that appears to be overexpressed in several human neoplasms. The aim of this review is to provide insights into the role of UBE4B ubiquitin ligase in DDR and its association with p53 expression, shedding light particularly on the molecular mechanisms of carcinogenesis. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

An increase in life expectancy due to improvements in healthcare, in parallel with high percentage of injures, because of traffic accidents and sport activities, has emerged as the primary reasons for the replacements of lost, infected, and damaged bones. Combined with tissue engineering, this is an area of great interest to regenerative medicine. Novel scaffolds development, providing a suitable environment that can favor osteoinduction for the newly formed bone is needed. Composite porous hydrogels, based on alginate and chitosan with the dispersed phase from powders of bioceramics, such as hydroxyapatite (HAp), are recently developed for this reason. This work presents a reverse and novel approach, where these two popular hydrogels are infiltrated in a 3D HAp-scaffold. More specifically, HAp is obtained from aragonite from cuttlefish bone via hydrothermal transformation. This reinforcement of HAp with alginate or chitosan hydrogels, through infiltration method gives to the final product proper mechanical potential for hard tissue regeneration. The structure of the produced scaffolds resembles the microstructure and the texture of the natural bone. These advanced scaffolds are easily handled by the surgeon while maintaining their porous structure during the implantation process to promote the regeneration of newly formed bone tissue. In particular, once such a scaffold is implanted in an area where the bone tissue is lost, biological liquids will be able to penetrate into the pores of the lyophilized composite scaffold. The polymeric matrix will then be dissolved and the remaining HAp, or its precursor compounds, which will eventually transform into HAp, will promote osteoinduction. The worldwide availability and the low cost of cuttlefish bone, along with their biological-natural origin are attractive features making them highly sorted material used in the preparation of advanced scaffolds containing HAp for applications in biomedicine. The optimization of the fabrication technique is required to unravel the endless potential of biomaterials, shedding light on this promising interdisciplinary field, which includes both tissue engineering and drug delivery system approaches. © Springer Nature Singapore Pte Ltd 2019.

In this minireview, we refer to recent results as far as the Platelet Activating Factor (PAF) inhibitors are concerned. At first, results of organic compounds (natural and synthetic ones and specific and nonspecific) as inhibitors of PAF are reported. Emphasis is given on recent results about a new class of the so-called metal-based inhibitors of PAF. A small library of 30 metal complexes has been thus created; their anti-inflammatory activity has been further evaluated owing to their inhibitory effect against PAF in washed rabbit platelets (WRPs). In addition, emphasis has also been placed on the identification of preliminary structure-activity relationships for the different classes of metal-based inhibitors. © 2017 Vasiliki D. Papakonstantinou et al.

Purpose: The use of nanoparticles has seen exponential growth in the area of health care, due to the unique physicochemical properties of nanomaterials that make them desirable for medical applications. The aim of this study was to examine the effects of crystal phase-nanostructured titanium dioxide particles on bioactivity/cytotoxicity in breast cancer epithelial cells. Materials and methods: Cultured Michigan Cancer Foundation (MCF)-7 and human breast adenocarcinoma (MDA-MB-468) breast cancer epithelial cells were exposed to ultraviolet A light (wavelength 350 nm) for 20 minutes in the presence of aqueous dispersions of two different nanostructured titanium dioxide (TiO2) crystal phases: anatase and an anatase-rutile mixture. Detailed characterization of each titanium dispersion was performed by dynamic light scattering. A 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) colorimetric assay was employed to estimate the percentage of viable cells after each treatment. Western blot analysis of protein expression and characterization, as well as a deoxyribonucleic acid (DNA)-laddering assay, were used to detect cell apoptosis. Results: Our results documented that 100% anatase TiO2 nanoparticles (110-130 nm) exhibited significantly higher cytotoxicity in the highly malignant MDA-MB-468 cancer cells than anatase-rutile mixtures (75%/25%) with the same size. On the contrary, MCF-7 cells (characterized by low invasive properties) were not considerably affected. Exposure of MDA-MB-468 cells to pure anatase nanoparticles or anatase-rutile mixtures for 48 hours resulted in increased proapoptotic Bax expression, caspase-mediated poly(adenosine diphosphate ribose) polymerase (PARP) cleavage, DNA fragmentation, and programmed cell death/apoptosis. Conclusion: The obtained results indicated that pure anatase TiO2 nanoparticles exhibit superior cytotoxic effects compared to anatase-rutile mixtures of the same size. The molecular mechanism of TiO2 nanoparticle cytotoxicity involved increased Bax expression and caspase-mediated PARP inactivation, thus resulting in DNA fragmentation and cell apoptosis. © 2014 Lagopati et al.

Nuclear Medicine provides efficient tools for cancer therapy using compounds labelled with radionuclides that emit beta-particles, alpha-particles or Auger electrons. With their short path lengths, they destroy mainly targeted cancer cells with limited side effects. Ideal application for targeted radionuclide therapy demands radionuclides' physical, radiobiological and radiochemical properties to be well known. These radionuclides are produced with the desirable characteristics for their application in Nuclear Medicine radiopharmaceutical therapy. Furthermore, measurements of absorbed dose to the abnormal and to the normal tissue, in a patient-specific point of view, enhance therapy effectiveness. Dosimetry is a valuable tool for the decision of a successful treatment that will give impressive anti-tumour results and favourable tumour-to-normal tissue ratios. This article will be a review of the contributions both in the production of the radionuclides - dedicated to radiopharmaceutical therapy - as well as in the individualized dosimetric methods referred in the literature for each radionuclide used in Nuclear Medicine therapy. Many dose-calculation methods and mathematical codes used will be referred in detail. © 2013 Bentham Science Publishers.

This study presents an attempt to compare individualised palliative treatment absorbed doses, by planar images data and Monte Carlo simulation, in two in vivo treatment cases, one of bone metastases and the other of liver lesions. Medical Internal Radiation Dose schema was employed to estimate the absorbed doses. Radiopharmaceutical volume distributions and absorbed doses in the lesions as well as in critical organs were also calculated by Monte Carlo simulation. Individualised planar data calculations remain the method of choice in internal dosimetry in nuclear medicine, but with the disadvantage of attenuation and scatter corrections lack and organ overlay. The overall error is about 7 % for planar data calculations compared with that using Monte Carlo simulation. Patient-specific three-dimensional dosimetric calculations using single-photon emission computed tomography with a parallel computed tomography study is proposed as an accurate internal dosimetry with the additional use of dose-volume histograms, which express dose distributions in cases with obvious inhomogeneity. © The Author 2011. Published by Oxford University Press. All rights reserved.

Optimum treatment planning of patients suffering from painful skeletal metastases requires accurate calculations concerning absorbed dose in metastatic lesions and critical organs, such as red marrow. Delivering high doses to tumor cells while limiting radiation dose to normal tissue, is the key for successful palliation treatment. The aim of this study is to compare the dosimetric calculations, obtained by Monte Carlo (MC) simulation and the MIRDOSE model, in therapeutic schemes of skeleton metastatic lesions, with Rhenium-186 (Sn)-HEDP and Samarium-153 -EDTMP. A bolus injection of 1295 MBq (35mCi) Re-186-HEDP was infused in 11 patients with multiple skeletal metastases. The administered dose for the 8 patients who received Sm-153 was 1 mCi /kg. Planar scintigraphic images for the two groups of patients were obtained, 24 h, 48 h and 72 h post injection, by an Elscint Apex SPX gamma camera. The images were processed, utilizing ROI quantitative methods, to determine residence times and radionuclide uptakes. Dosimetric calculations were performed using the patient specific scintigraphic data by the MIRDOSE3 code of MIRD. Also, MCNPX was employed, simulating the distribution of the radioisotope in the ROI and calculating the absorbed doses in the metastatic lesion, and in critical organs. Summarizing, there is a good agreement between the results, derived from the two pathways, the patient specific and the mathematical, with a deviation of less than 9% for planar scintigraphic data compared to MC, for both radiopharmaceuticals.

Metaiodobenzylguanidine (MIBG) scintigraphy is used to image tumors of neuroendocrine origin and study disorders of sympathetic innervation of the myocardium. Scintigraphic imaging methods offer the possibility of qualitative and quantitative assessment of tracer concentration. Accurate correction for the physical degrading factors (attenuation, scatter, partial volume effects) is demanded. An analytical study of the I-123 energy spectrum, scattering and attenuation contribution to the resulting image of an I-123 MIBG scintigraphy, has been undergone, so as to improve the data that could be collected by I-123-MIBG use. In this work, quantitative data were gathered at various source depths, volumes and crystal to phantom distances to determine the effect of these variables on source activity data. The final image is being extracted from the combination of three different images, each and every one being acquired by a different energy window. The middle one has been obtained from the main I-123 photopeak and the others, from the left and right peaks respectively. The problem of Compton scattering as the dominant photon interaction phenomenon and its impact on both the quality of clinical images and the accuracy of quantitative analysis is taken into consideration for a scatter modeling in non-uniform media.