Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented

Fertility preservation in ovarian tumours

A considerable number of patients with a cancer diagnosis are of childbearing age and have not satisfied their desire for a family. Despite ovarian cancer (OC) usually occurring in older patients, 3%–14% are diagnosed at a fertile age with the overall 5-year survival rate being 91.2% in women ≤44 years of age when it is found at 1A–B stage. In this scenario, testing the safety and the efficacy of fertility sparing strategies in OC patients is very important overall in terms of quality of life. Unfortunately, the lack of randomised trials to validate conservative approaches does not guarantee the safety of fertility preservation strategies. However, evidence-based data from descriptive series suggest that in selected cases, the preservation of the uterus and at least one part of the ovary does not lead to a high risk of relapse. This conservative surgery helps to maintain organ function, giving patients of childbearing age the possibility to preserve their fertility. We hereby analysed the main evidence from the international literature on this topic in order to highlight the selected criteria for conservative management of OC patients, including healthy BRCA mutations carriers

Analysis of fossil planktonic foraminifera: the sieve mesh effect

The choice of the sediment size fraction in the analysis of fossil planktonic foraminifera is of great importance in determining the composition of assemblages. In past studies several size fractions have been utilised. Imbrie and Kipp (1971) stated that “smaller fractions give rise to too many uncertainties in the identification of small specimens and require too long to process. Large mesh size yield undesiderable loss of small species, and small specimens of larger species”. The adoption of coarser sieve meshes has the effect to reduce the percentages of small sized (usually living in cold waters) species (Bé and Hutson, 1977). In a comparison between >63 μm and >150 μm size-fraction of planktonic foraminifera assemblages from NW Atlantic Ocean, Smart (2002), stated that because particular smaller species are either under-represented or even absent from the larger (>150 μm) size-fraction, the smaller (>63 μm) size-fraction must be included in studies of planktonic foraminifera. Di Donato et al. (2008) highlighted in the >150 μm size fraction of a core from the Tyrrhenian Sea, a great loss of the small-sized species Turborotalita quinqueloba in glacial samples, where this species is very abundant. This caused an increase in warm water species such as Globigerinoides ruber, apparently reaching typical Holocene values in some full glacial levels. From the above mentioned statements, it is clear that treatment changes can strongly influence the results of palaeoclimatic reconstructions based on planktonic foraminiferal assemblages. As stated by Aitchison (1986, 1992) scale invariance and subcompositional coherence are fundamental properties of the compositional data analysis (CODA). The main goal of this paper is to verify if the variable relationships pointing out from CODA of foraminiferal assemblages are or not influenced by the size fraction and, more in general, to test the robustness of CODA respect to treatment changes related to different preparation techniques for the analysis of planktonic foraminifera

Immunotherapy in endometrial cancer: new scenarios on the horizon

This extensive review summarizes clinical evidence on immunotherapy and targeted therapy currently available for endometrial cancer (EC) and reports the results of the clinical trials and ongoing studies. The research was carried out collecting preclinical and clinical findings using keywords such as immune environment, tumor infiltrating lymphocytes, programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, immune checkpoint inhibitors, anti-PD-1/PD-L1 antibodies and others’ on PubMed. Finally, we looked for the ongoing immunotherapy trials on ClinicalTrials.gov. EC is the fourth most common malignancy in women in developed countries. Despite medical and surgical treatments, survival has not improved in the last decade and death rates have increased for uterine cancer in women. Therefore, identification of clinically significant prognostic risk factors and formulation of new rational therapeutic regimens have great significance for enhancing the survival rate and improving the outcome in patients with advanced or metastatic disease. The identification of genetic alterations, including somatic mutations and microsatellite instability, and the definition of intracellular signaling pathways alterations that have a major role in in tumorigenesis is leading to the development of new therapeutic options for immunotherapy and targeted therapy

PHK from phenol hydroxylase of Pseudomonas sp. OX1. Insight into the role of an accessory protein in bacterial multicomponent monooxygenases

Bacterial multicomponent monooxygenases (BMMs) are members of a wide family of diiron enzymes that use molecular oxygen to hydroxylate a variety of aromatic compounds. The presence of genes encoding for accessory proteins not involved in catalysis and whose role is still elusive, is a common feature of the gene clusters of several BMMs, including phenol hydroxylases and several soluble methane monooxygenases. In this study we have expressed, purified, and partially characterized the accessory component PHK of the phenol hydroxylase from Pseudomonas sp. OX1, a bacterium able to degrade several aromatic compounds. The phenol hydroxylase (ph) gene cluster was expressed in Escherichia coli/JM109 cells in the absence and in the presence of the phk gene. The presence of the phk gene lead to an increase in the hydroxylase activity of whole recombinant cells with phenol. PHK was assessed for its ability to interact with the active hydroxylase complex. Our results show that PHK is neither involved in the catalytic activity of the phenol hydroxylase complex nor required for the assembly of apo-hydroxylase. Our results suggest instead that this component may be responsible for enhancing iron incorporation into the active site of the apo-hydroxylase

Ovarian cancer metastasis to the breast: a case report and review of the literature

Although ovarian cancer often presents as a widespread disease, metastases to the breast and/or axillary lymph nodes are a very rare event, accounting for only 0.03-0.6% of all breast cancers. Its early recognition and accurate distinction from primary breast cancer are of crucial importance to choose an adequate systemic therapy over unnecessary surgeries. We presented the case of a 53-year-old woman who was diagnosed with breast metastases 2 years after the diagnosis of advanced primary serous ovarian cancer. The patient underwent primary cytoreductive surgery and platinum-based chemotherapy in combination with bevacizumab, followed by bevacizumab maintenance for 18 months. After 2 years of negative follow-ups, the disease unexpectedly spread to the left breast and axillary lymph nodes. No axillary lymph node dissection or breast surgery was performed. The patient received axillary radiotherapy and multiple chemotherapy lines: gemcitabine/cisplatin, liposomal doxorubicin, topotecan, olaparib/cediranib, paclitaxel, and cisplatin. Unfortunately, none of these treatments improved her prognosis and she died 3 years after the disease recurrence. Ovarian cancer metastasis to the breast reveals a disseminated disease with a poor prognosis. Currently, no valid treatment options are available as the disease shows multidrug chemoresistance. In the era of precision medicine, the characterization of genetic and molecular markers may play a role in offering new promising targeted therapies

Upper limb work-related musculoskeletal disorders in operating room nurses: A multicenter cross-sectional study

This study aimed to evaluate the association between personal and job characteristics and the risk of upper limb work-related musculoskeletal disorders (WMSDs) among operating room nurses (ORNs). To this end, we collected data from 148 ORNs working at 8 Italian hospitals and measured any upper limb disabilities experienced in the previous year using the Italian version of the disabilities of the arm, shoulder and hand (DASH) questionnaire. The associations between personal and job characteristics and risk of upper limb WMSDs were estimated by unconditional logistic regression models. The prevalence of upper limb WMSDs was 45.9%. Multivariate analysis showed the \u201cfemale gender\u201d and \u201cmonthly hours spent working as a scrub nurse\u201d to be directly associated with a higher DASH score (adjusted OR for gender = 5.37, 95% CI: 1.65\u201317.51, p < 0.01; adjusted OR for monthly hours as scrub nurse = 3.09, 95% CI: 1.33\u20137.19, p < 0.01). Overall, our findings indicate that a full-time job (>120 h/month) as a scrub nurse significantly increases the risk of developing upper limb WMSDs among female ORNs. Thus, to reduce such risk in this particularly sensitive population, we recommend urgent implementation of ergonomic interventions on surgical equipment alongside job rotation and medical surveillance programs

Gamma-ray anisotropies from dark matter in the Milky Way: the role of the radial distribution

The annihilation of dark matter particles in the halo of galaxies may end up into gamma rays, which travel almost unperturbed till to their detection at Earth. This annihilation signal can exhibit an anisotropic behavior quantified by the angular power spectrum, whose properties strongly depend on the dark matter distribution and its clumpiness. We use high resolution pure dark matter N-body simulations to quantify the contribution of different components (main halo and satellites) to the global signal as a function of the analytical profile adopted to describe the numerical results. We find that the smooth main halo dominates the angular power spectrum of the gamma-ray signal up to quite large multipoles, where the sub-haloes anisotropy signal starts to emerge, but the transition multipole strongly depends on the assumed radial profile. The extrapolation down to radii not resolved by current numerical simulations can affect both the normalization and the shape of the gamma-ray angular power spectrum. For the sub-haloes described by an asymptotically cored dark matter distribution, the angular power spectrum shows an overall smaller normalization and a flattening at high multipoles. Our results show the criticality of the dark matter density profile shape in gamma-ray anisotropy searches, and evaluate quantitatively the intrinsic errors occurring when extrapolating the dark matter radial profiles down to spatial scales not yet explored by numerical simulations.Comment: 7 pages, 8 figures. It matches the version published in MNRA

Expression and purification of the recombinant subunits of toluene/o-xylene monooxygenase and reconstitution of the active complex.

This paper describes the cloning of the genes coding for each component of the complex of toluene/o-xylene monooxygenase from Pseudomonas stutzeri OX1, their expression, purification and characterization. Moreover, the reconstitution of the active complex from the recombinant subunits has been obtained, and the functional role of each component in the electron transfer from the electron donor to molecular oxygen has been determined. The coexpression of subunits B, E and A leads to the formation of a subcomplex, named H, with a quaternary structure (BEA)2, endowed with hydroxylase activity. Tomo F component is an NADH oxidoreductase. The purified enzyme contains about 1 mol of FAD, 2 mol of iron, and 2 mol of acid labile sulfide per mol of protein, as expected for the presence of one [2Fe-2S] cluster, and exhibits a typical flavodoxin absorption spectrum. Interestingly, the sequence of the protein does not correspond to that previously predicted on the basis of DNA sequence. We have shown that this depends on minor errors in the gene sequence that we have corrected. C component is a Rieske-type ferredoxin, whose iron and acid labile sulfide content is in agreement with the presence of one [2Fe-2S] cluster. The cluster is very sensitive to oxygen damage. Mixtures of the subcomplex H and of the subunits F, C and D are able to oxidize p-cresol into 4-methylcathecol, thus demonstrating the full functionality of the recombinant subunits as purified. Finally, experimental evidence is reported which strongly support a model for the electron transfer. Subunit F is the first member of an electron transport chain which transfers electrons from NADH to C, which tunnels them to H subcomplex, and eventually to molecular oxyge