Malignant Transformation of Giant Cell Tumour of Bone: A Review of Literature and the Experience of a Referral Centre

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1–9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.     

Polygenic Risk of Hypertriglyceridemia Is Modified by BMI

Background: Genetic risk scores (GRSs) have partially improved the understanding of the etiology of moderate hypertriglyceridemia (HTG), which until recently was mainly assessed by secondary predisposing causes. The main objective of this study was to assess whether this variability is due to the interaction between clinical variables and GRS. Methods: We analyzed 276 patients with suspected polygenic HTG. An unweighted GRS was developed with the following variants: c.724C > G (ZPR1 gene), c.56C > G (APOA5 gene), c.1337T > C (GCKR gene), g.19986711A > G (LPL gene), c.107 + 1647T > C (BAZ1B gene) and g.125478730A > T (TRIB gene). Interactions between the GRS and clinical variables (body mass index (BMI), diabetes mellitus, diet, physical activity, alcohol consumption, age and gender) were evaluated. Results: The GRS was associated with triglyceride (TG) concentrations. There was a significant interaction between BMI and GRS, with the intensity of the relationship between the number of alleles and the TG concentration being greater in individuals with a higher BMI. Conclusions: GRS is associated with plasma TG concentrations and is markedly influenced by BMI. This finding could improve the stratification of patients with a high genetic risk for HTG who could benefit from more intensive healthcare interventions.     

Whole Body Vibration Improves Brain and Musculoskeletal Health by Modulating the Expression of Tissue-Specific Markers: FNDC5 as a Key Regulator of Vibration Adaptations

Whole body vibration (WBV) is well known to exert beneficial effects on multiple tissues, improving synaptic transmission, muscle mass, bone quality, and reducing anxiety and depressive behavior. However, the underlying molecular mechanisms are not yet fully understood, and organs and tissues may respond differently to the vibratory stimulus depending on multiple factors. Therefore, we investigated the WBV effects on the brain and musculoskeletal tissue of 4-month-old young mice, evaluating synaptic plasticity by electrophysiological recordings and tissue organization by histology and histomorphometric analysis. Specifically, WBV protocols were characterized by the same vibration frequency (45 Hz), but different in vibration exposure time (five series of 3 min for the B protocol and three series of 2 min and 30 s for the C protocol) and recovery time between two vibration sessions (1 min for the B protocol and 2 min and 30 s for the C protocol). In addition, immunohistochemistry was conducted to evaluate the expression of fibronectin type III domain-containing protein 5 (FNDC5), as well as that of tissue-specific markers, such as brain-derived neurotrophic factor (BDNF) in brain, myostatin in muscle and collagen I (COL-1) in bone. Our results suggest that the WBV effects depend closely on the type of protocol used and support the hypothesis that different organs or tissues have different susceptibility to vibration. Further studies will be needed to deepen our knowledge of physiological adaptations to vibration and develop customized WBV protocols to improve and preserve cognitive and motor functions.     

The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA. Several findings highlighted the ability of some chemotherapeutics to induce immunogenic cell death (ICD), which is defined by the cell surface translocation of Calreticulin (CALR) via dissociation of the PP1/GADD34 complex. In this regard, we computationally predicted the ability of SIX2G to induce CALR exposure by interacting with the PP1 RVxF domain. We then assessed both the potential cytotoxic and immunogenic activity of SIX2G on in vitro models of multiple myeloma (MM), which is an incurable hematological malignancy characterized by an immunosuppressive milieu. We found that the treatment with SIX2G inhibited cell viability by inducing G2/M phase cell cycle arrest and apoptosis. Moreover, we observed the increase of hallmarks of ICD such as CALR exposure, ATP release and phospho-eIF2α protein level. Through co-culture experiments with immune cells, we demonstrated the increase of (i) CD86 maturation marker on dendritic cells, (ii) CD69 activation marker on cytotoxic T cells, and (iii) phagocytosis of tumor cells following treatment with SIX2G, confirming the onset of an immunogenic cascade. In conclusion, our findings provide a framework for further development of SIX2G as a new potential anti-MM agent.     

Protein breakdown during the preparation of frozen batter-coated squid rings

The objective of this paper was to study the main chemical and microstructural changes in squid proteins during processing as a frozen batter-coated product using different coatings. Protein bands of the squid and of the batters used for coating were studied using SDS-PAGE. It is concluded that it is not only the proteins of the layer of batter, which are directly exposed both to the frying oil and to freezing temperatures, that deteriorate during the preparation process, the protein fraction of the squid substrate, mainly the myofibrillar proteins, is also degraded. At a microstructural level, big voids are generated during freezing as a consequence of the packing of the fibres, although the size of these voids decreases after final frying. After this step of the process, the central sarcoplasm is still visible but has been altered by coagulation of the sarcoplasmic proteins and the sarcolemma is observed to be separate from the myofibrillar package.     

Analysis of Water-Soluble Vitamins in Honey by Isocratic RP-HPLC

An isocratic RP-HPLC method has been developed for the identification and quantification of water-soluble vitamins in honey. The mobile phase tested was an aqueous solution of sulphuric acid and the detection was carried out simultaneously by UV and fluorescence. The separation of vitamins C (l-ascorbic acid), B₁ (thiamine), B₃N (nicotinamide), B₃H (nicotinic acid), B₅ (d-pantothenic acid) and B₆ (pyridoxine) is achieved in these conditions in 15 min. The addition to the mobile phase of methanol 2 %?v/v reduced significantly the analysis time in the separation of these vitamins up to 10 min. Moreover, in presence of a cationic surfactant hexadecyltrimethylammonium bromide (CTAB) in the mobile phase, the separation of vitamin C, B₁, B₃N, B₃H, B₂ (riboflavin) and B₆ is possible in 6 min. The combination of both mobile phases, H₂SO₄/methanol and H₂SO₄/methanol/CTAB, has been applied to the analysis, in isocratic mode, of several monofloral honeys (rosemary, thyme, lavender, chestnut, echium) and a honeydew honey in a short time analysis.     

Effect of processing for saponin removal on fungal contamination of quinoa seeds (Chenopodium quinoa Willd.)

Incidence of fungal contamination of quinoa seeds from three locations (Salar de Uyuni, Bolivia; Salta and Tucumán provinces, Argentina) was analyzed in samples with and without treatment to remove saponins (wet method). In processed samples, the percentage of infection was reduced. Distribution of the different fungal genera was not homogeneous in the three locations (p<0.05), although Penicillium and Aspergillus were the most prevalent contaminants, regardless the geographic origin of the samples. Other genera, such as Eurotium, Fusarium, Phoma, Ulocladium, Mucor and Rhizopus were less frequently isolated. Absidia, Alternaria, Cladosporium, Dreschlera, Epicoccum and Monascus were sporadically encountered. Significant differences (p<0.05) in the distribution of fungal genera in samples with and without saponins from each location were observed. In all cases, processing caused a decrease of Aspergillus incidence, while increased the proportion of Penicillium, Eurotium, Mucor and Rhizopus indicating that these genera were part of the internal mycota. A. flavus and A. niger were the dominating species of genus Aspergillus. A similar pattern of prevalent Penicillium species was observed in samples with and without saponins, since P. aurantiogriseum, P.chrysogenum, P. citrinum and P. crustosum were always present in high number, although their relative density was variable according to the geographic origin of samples. Mycotoxin-producing ability of most representative species was also determined. Toxigenic strains of A. flavus (aflatoxins and cyclopiazonic acid), A. parasiticus (aflatoxins), P. citrinum (citrinin) and P. griseofulvum (cyclopiazonic acid) were found. None of the A. niger isolates was ochratoxin A producer. The above mentioned mycotoxins were not detected in the samples analyzed.     

Self-foaming diphenolic acid benzoxazine

This work concerns the investigation of porous polybenzoxazines based on the non-toxic renewable diphenolic acid. The approach described relies on the in situ generation of foaming agent (CO₂) during the thermal curing. For this purpose, the previously synthesized benzoxazine monomer from diphenolic acid was thermally polymerized at different temperatures. As the beginning of decarboxylation is about 200 °C, we selected five foaming temperatures (T_f) ranging from 190 to 230 °C. The influence of the foaming temperature on the cellular structure and its dependency on final properties is discussed.     

Influence of different carbon nanostructures on the electrocatalytic activity and stability of Pt supported electrocatalysts

Commercially available graphitized carbon nanofibers and multi-walled carbon nanotubes, two carbon materials with very different structure, have been functionalized in a nitric–sulfuric acid mixture. Further on, the materials have been platinized by a microwave assisted polyol method. The relative degree of graphitization has been estimated by means of Raman spectroscopy and X-ray diffraction while the relative concentration of oxygen containing groups has been estimated by X-ray photoelectron spectroscopy, which resulted in a graphitic character trend: Pt/GNF > Pt/F-GNF ? Pt/MWCNT > Pt/F-MWCNT. Transmission electron microscopy showed that the Pt particle size is around 3 nm for all samples, which was similar to the crystallite size obtained by X-ray diffraction. The activity towards electrochemical reduction of oxygen has been quantified using the thin-film rotating disk electrode, which has shown that all the samples have a better activity than the commercially available electrocatalysts. The trend obtained for the graphitic character maintained for the electrochemical activity, while the reverse trend has been obtained for the accelerated ageing test. Long-term potential cycling has demonstrated that the functionalization improves the stability for multi-walled carbon nanotubes, at the cost of decreased activity.