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.     

Accuracy of FIB-4 to Detect Elevated Liver Stiffness Measurements in Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Referral Centers

The identification of advanced fibrosis by applying noninvasive tests is still a key component of the diagnostic algorithm of NAFLD. The aim of this study is to assess the concordance between the FIB-4 and liver stiffness measurement (LSM) in patients referred to two liver centers for the ultrasound-based diagnosis of NAFLD. Fibrosis 4 Index for Liver Fibrosis (FIB-4) and LSM were assessed in 1338 patients. A total of 428 (32%) had an LSM ≥ 8 kPa, whereas 699 (52%) and 113 (9%) patients had an FIB-4 < 1.3 and >3.25, respectively. Among 699 patients with an FIB-4 < 1.3, 118 (17%) had an LSM ≥ 8 kPa (false-negative FIB-4). This proportion was higher in patients ≥60 years, with diabetes mellitus (DM), arterial hypertension or a body mass index (BMI) ≥ 27 kg/m². In multiple adjusted models, age ≥ 60 years (odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.19–3.23)), DM (OR = 2.59, 95% CI 1.63–4.13), body mass index (BMI) ≥ 27 kg/m² (OR = 2.17, 95% CI 1.33–3.56) and gamma-glutamyltransferase ≥ 25 UI/L (OR = 2.68, 95% CI 1.49–4.84) were associated with false-negative FIB-4. The proportion of false-negative FIB-4 was 6% in patients with none or one of these risk factors and increased to 16, 31 and 46% among those with two, three and four concomitant risk factors, respectively. FIB-4 is suboptimal to identify patients to refer to liver centers, because about one-fifth may be false negative at FIB-4, having instead an LSM ≥ 8 KPa.     

New Insights into Dose-Dependent Effects of Curcumin on ARPE-19 Cells

Opposing dose-dependent effects of curcumin (Cur) have been documented in Retinal Pigment Epithelium (RPE); therefore, to shed the light on the mechanisms of action is crucial for ophthalmic applications. On this basis we explored new insights about the dose-dependent mechanisms triggered by Cur in human retinal pigment epithelial cells (ARPE-19). Three concentrations (0.01 mM; 0.05 mM; 0.1 mM) of Cur were tested, followed by morphological, molecular, and functional analysis of the cells. Cur 0.01 mM promotes a significant increase in cell proliferation, not affecting cell cycle progression and apoptosis; by contrast, Cur 0.05 mM and 0.1 mM block cellular proliferation and trigger S-phase cell cycle arrest without inducing apoptosis. The observation of neuronal-like morphological changes in Cur 0.05 mM and 0.1 mM were not associated with neuronal differentiation, as observed by the quantification of Neurofilament-200 and by the analysis of voltage-dependent currents by patch clamp. Evaluation of autophagic markers LC3BII and p62 revealed significant modulations, suggesting an important activation of autophagy in ARPE-19 cells treated with Cur 0.05 mM and Cur 0.1 mM; conversely, Cur 0.01 mM did not affect autophagy. Altogether, our findings show new dose-dependent mechanisms of action of Cur that suggest a wide therapeutic application in ocular diseases with different pathogenesis (i.e., proliferative vitreoretinopathy or Age-Related Macular Degeneration).     

The Generation of Nitric Oxide from Aldehyde Dehydrogenase-2: The Role of Dietary Nitrates and Their Implication in Cardiovascular Disease Management

Reduced bioavailability of the nitric oxide (NO) signaling molecule has been associated with the onset of cardiovascular disease. One of the better-known and effective therapies for cardiovascular disorders is the use of organic nitrates, such as glyceryl trinitrate (GTN), which increases the concentration of NO. Unfortunately, chronic use of this therapy can induce a phenomenon known as “nitrate tolerance”, which is defined as the loss of hemodynamic effects and a reduction in therapeutic effects. As such, a higher dosage of GTN is required in order to achieve the same vasodilatory and antiplatelet effects. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a cardioprotective enzyme that catalyzes the bio-activation of GTN to NO. Nitrate tolerance is accompanied by an increase in oxidative stress, endothelial dysfunction, and sympathetic activation, as well as a loss of the catalytic activity of ALDH2 itself. On the basis of current knowledge, nitrate intake in the diet would guarantee a concentration of NO such as to avoid (or at least reduce) treatment with GTN and the consequent onset of nitrate tolerance in the course of cardiovascular diseases, so as not to make necessary the increase in GTN concentrations and the possible inhibition/alteration of ALDH2, which aggravates the problem of a positive feedback mechanism. Therefore, the purpose of this review is to summarize data relating to the introduction into the diet of some natural products that could assist pharmacological therapy in order to provide the NO necessary to reduce the intake of GTN and the phenomenon of nitrate tolerance and to ensure the correct catalytic activity of ALDH2.     

Chemical characterisation of Thymus populations belonging from Southern Italy

The genus Thymus L. consists of many species of herbaceous perennials and sub-shrubs. A chemical characterisation of a collection of Thymus spp. originated from regions of Southern Italy was performed using GC and GC/MS. The accessions were collected from various natural habitats of the Basilicata and Puglia Regions and transferred into a new uniform environment. The study showed that amongst the 22 components of the oils the most recurrent ones were geraniol, thymol and α-terpinene followed by linalool, citral and trans-caryophillene. Cluster analysis led to the identification of two chemotypes: geraniol and thymol/α-terpinene; only a biotype remained separate from all others, probably because of its high content linalool (58%).     

<Superscript>1</Superscript>H NMR characterization of milk lipids: A comparison between cow and buffalo milk

Characterization of the lipid fraction of raw cow and buffalo milk samples, collected in different breeding areas in Apulia, a region of southern Italy, were performed by means of ¹H NMR. The aim of this work was to establish whether FA composition data obtained by ¹H NMR can be used in the differentiation of buffalo and cow milk samples according to species. A complete assignment of the signals present in the spectrum was attempted by COSY, heteronuclear coherence spectra. Quantification of FA was carried out by inserting the integrals of particular peaks in suitable calculations. Multivariate statistical analysis, conducted on the results of the quantification, permitted buffalo and cow milks to be distinguished.     

Compositional studies: antioxidant and antidiabetic activities of Capparis decidua (Forsk.) Edgew

Capparis decidua is one of the traditional remedies used for various medicinal treatments in Pakistan. This study presents the determination of proximate composition, amino acids, fatty acids, tocopherols, sterols, glucosinolate and phenolic content in extracts obtained from different aerial parts of C. decidua, as well as their antidiabetic and antioxidant activity. All examined extracts were prominently rich in phenolics and glucosinates, and they showed potent antidiabetic and antihemolytic activity. The present study could be helpful in developing medicinal preparations for the treatment of diabetes and related symptoms.     

Evaluation of Epigenetic and Radiomodifying Effects during Radiotherapy Treatments in Zebrafish

Radiotherapy is still a long way from personalizing cancer treatment plans, and its effectiveness depends on the radiosensitivity of tumor cells. Indeed, therapies that are efficient and successful for some patients may be relatively ineffective for others. Based on this, radiobiological research is focusing on the ability of some reagents to make cancer cells more responsive to ionizing radiation, as well as to protect the surrounding healthy tissues from possible side effects. In this scenario, zebrafish emerged as an effective model system to test for radiation modifiers that can potentially be used for radiotherapeutic purposes in humans. The adoption of this experimental organism is fully justified and supported by the high similarity between fish and humans in both their genome sequences and the effects provoked in them by ionizing radiation. This review aims to provide the literature state of the art of zebrafish in vivo model for radiobiological studies, particularly focusing on the epigenetic and radiomodifying effects produced during fish embryos’ and larvae’s exposure to radiotherapy treatments.