Potential role of p53 protein as a novelbiomarker of sperm quality, able to predict thesuccess of ART techniques. EcoFoodFertility Project

Introduction: Protein p53 is well known as “The guardian of genome”; it changes its concentration in human spermatozoa DNAin relation to the damage of the latter. It has been suggested thatthe role of the p53 ancestral gene was to ensure the integrity ofthe genomic germline and the fidelity of the evelopment process.The aim of this study is to evaluate if different concentrations of p53 protein in human spermatozoa could influence embryo quality and pregnancy rate and possibly representing a potential predictive marker of sperm quality for successful fertilization .Methods: From July 2013 to June 2017 we have examinatedretrospectively 79 couples with 2-5 years of infertility history.Males had an average age of 27 ± 7,5 years, sperm concentrationof 33,8 ± 6,2 mil/ml, progressive motility of 41,4 ± 8,3 and a typical morphology of 16,5 ± 3,5 according to Kruger’s method. We have divided the couples on the basis of p53 levels: Group A:0,35–1,65 ng/mil (21 males); Group B: 1,66–3,57 ng/mil (32 males);Group C: 3,58–14,53 ng/mil (26 males). We have evaluated thenumber of embryos at stage of 6–8 cells, btained at the third dayof embryo development, in these three different group. In order toevaluate the concentration of p53 protein, we first proceeded toa DNA extraction with forensic method and then to a quantification p53 protein with ELISA-immunoenzymatic assay, expressedin ng/million of spermatozoa.Results: We have observed different percentage of embryo development at stage of 6-8 cells in the third day and different pregnancy rate (PR):Group A: 101 embryos at 6-8 cells/ 147 total number of obtained embryos in this group (68,4%) and PR = 52,38%.Group B: 128/240 (53,5%); PR = 37,50%; Group C: 79/216 (36,1%);PR = 7,69%. These results support the hypothesis that an high con-centration of p53 in human sperm DNA is associated to a low percentage of embryos able to reach the stage of 6-8 cells in the third day of development and also to a lower pregnancy rate. So p53 levels can be considered as a predictive value to embryo development and pregnancy rate.Conclusions: Protein p53 is a sequence-specific transcriptionfactor that responds to a wide variety of stress signals (environ-mental insults and bad lifestyle) as we are investigating within theecofoodfertility project. Particularly quantitative research of p53could be considered as a novel biomarker of sperm quality, able topredict the success of ART echniques, and could open a new roadfor infertility diagnosis

The Role of Human Semen as an Early and Reliable Tool of Environmental Impact Assessment on Human Health

Several studies have shown a dramatic reduction of semen quality in many industrialized countries and infertility is becoming a public health top priority, whose incidence is associated to late-onset adult diseases, especially cancer, shorter life expectancy and trans-generational effects. The male reproductive system is particularly sensitive to a broad variety of reproductive and developmental toxicants, including many environmental pollutants and recent studies suggest that human semen is an early and sensitive environmental and health marker. A set of semen biomarkers is described for reproductive health effects in relation to environmental exposure, where human semen seems to be an early and sensitive source of biomarkers than blood to monitor high environmental pressure on human health. Environmental health should consider reproductive health and development, from intrauterine life to childhood and puberty: these are both vulnerable targets and high-value protection goals, inasmuch as they represent the future of our societies. Hence, biomarkers of reproductive health should be exploited as early signals of environmental pressure and increased risk of adverse chronic health effects so that the use of “human seminal model” might be the main objective to be considered in the agenda of public prevention policies for early detection and innovative programs of health surveillance in environmental risk areas

Comparison Process of Blood Heavy Metals Absorption Linked to Measured Air Quality Data in Areas with High and Low Environmental Impact

Air pollution is a problem shared by the entire world population, and researchers have highlighted its adverse effects on human health in recent years. The object of this paper was the relationship between the pollutants’ concentrations measured in the air and the quantity of pollutant itself inhaled by the human body. The area chosen for the study has a high environmental impact given the significant presence on the territory of polluting activities. The Acerra area (HI) has a waste-to-energy plant and numerous industries to which polluting emissions are attributed. This area has always been the subject of study as the numbers of cancer patients are high. A survey on male patients to evaluate the heavy metals concentrations in the blood was conducted in the two areas and then linked to its values aero-dispersed. Using the air quality data measured by the monitoring networks in two zones, one with high environmental impact (HI) and one with low environmental impact (LI), the chronicle daily intake (CDI) of pollutants inhaled by a single person was calculated. The pollutants considered in this study are PM10 and four heavy metals (As, Cd, Ni, Pb) constituting the typical particulates of the areas concerned. The CDI values calculated for the two zones are significantly higher in the HI zone following the seasonal pollution trend

A Comparative Analysis of Orexins in the Physio-Pathological Processes of the Male Genital Tract: New Challenges? A Review

Orexins A (OXA) and B (OXB) and their specific receptors, receptor 1 (OX1R) and 2 (OX2R) for orexins, are hypothalamic peptides involved in orchestrating several functions in the central nervous system and peripheral organs, including sleep, excitement, nutrition, reward, circadian rhythm, anxiety, cognition, and reproduction. The aim of this narrative review is, in particular, to speculate the role of orexins in the male genital tract of animal species and human beings. The experimental evidence collected in recent years assumed that in the testes of the animal species here described, orexins are directly involved in steroidogenesis and spermatogenesis regulation. In the epididymis, these peptides are locally synthesized, thus suggesting their role governing the fertilizing capability of the immature male gamete. In addition to playing a physiological role, orexins are involved in numerous inflammatory and/or neoplastic pathologies too. The expression of the orexinergic system in prostate cancer suggests that they might play a potential therapeutic function. Overall, the future directions of this literature review allow us to hypothesize a role of the orexinergic complex not only as a marker for the diagnosis of certain tumors affecting the male genital tract but also for the treatment of hypo/infertility condition

Presence of p53 Protein on Spermatozoa DNA: A Novel Environmental Bio-Marker and Implications for Male Fertility

Many studies suggest a direct relationship between toxic effects and an increase in the p53 protein on cellular DNA. For our studies, we used sperm DNA as an indicator of environmental toxic effects, dosing p53 quantitatively. To assess possible variations, we used semen samples from two homogeneous male groups living permanently in areas with different environmental impact. The toxic effects of the selected high environmental impact area are caused by both soil and air pollution, while the selected low environmental impact area is a nature reserve where there are no landfills, but only rural factories. As we work with reproductive cells, our interest was inevitably focused on sperm DNA damage and whether this damage could affect their fertilizing capacity. The length of telomeres and the quantification of protamines are being studied to better define the possible damage

The first report on detecting SARS-CoV-2 inside bacteria of the human gut microbiome: A case series on asymptomatic family members and a child with COVID-19

Many studies report the importance of using feces as source sample for detecting SARS-CoV-2 in patients with COVID-19 symptoms but who are negative to oropharyngeal/ nasopharyngeal tests. Here, we report the case of an asymptomatic child whose family members had negative results with the rapid antigen nasopharyngeal swab tests. The 21-month-old child presented with fever, diarrhea, bilateral conjunctivitis, and conspicuous lacrimation. In this study, analysis for the presence of SARS-CoV-2 in fecal samples by using Luminex technology allowed accurate detection of the presence of the viral RNA in the feces of the child and of all her relatives, which thus resulted to be positive but asymptomatic. It is the first time that SARS-CoV-2- is observed inside bacteria of the human gut microbiome and outside a matrix resembling extracellular bacterial lysates, in agreement with a bacteriophage mechanism with the images obtained by transmission electron microscopy (TEM), post-embedding immunogold, and by fluorescence microscope. In addition to the typical observations of respiratory symptoms, accurate evaluation of clinical gastrointestinal and neurological symptoms, combined with efficient highly sensitive molecular testing on feces, represent an efficient approach for detecting SARS-CoV-2, and for providing the correct therapy in challenging COVID-19 cases, like the one here reported

The first report on detecting SARS-CoV-2 inside human fecal-oral bacteria: A case series on asymptomatic family members and a child with COVID-19

Many studies report the importance of using feces as source sample for detecting SARS-CoV-2 in patients with COVID-19 symptoms but who are negative to oropharyngeal/ nasopharyngeal tests. Here, we report the case of an asymptomatic child whose family members had negative results with the rapid antigen nasopharyngeal swab tests. The 21-month-old child presented with fever, diarrhea, bilateral conjunctivitis, and conspicuous lacrimation. In this study, analysis for the presence of SARS-CoV-2 in fecal samples by using Luminex technology allowed accurate detection of the presence of the viral RNA in the feces of the child and of all her relatives, which thus resulted to be positive but asymptomatic. It is the first time that SARS-CoV-2- is observed inside human fecal-oral bacteria and outside a matrix resembling extracellular bacterial lysates, in agreement with a bacteriophage mechanism with the images obtained by transmission electron microscopy (TEM), post-embedding immunogold, and by fluorescence microscope. In addition to the typical observations of respiratory symptoms, accurate evaluation of clinical gastrointestinal and neurological symptoms, combined with efficient highly sensitive molecular testing on feces, represent an efficient approach for detecting SARS-CoV-2, and for providing the correct therapy in challenging COVID-19 cases, like the one here reported

Polychlorinated Biphenyls (PCBs) in the Environment: Occupational and Exposure Events, Effects on Human Health and Fertility

In the last decade or so, polychlorinated biphenyls (PCBs) garnered renewed attention in the scientific community due to new evidence pointing at their continued presence in the environment and workplaces and the potential human risks related to their presence. PCBs move from the environment to humans through different routes; the dominant pathway is the ingestion of contaminated foods (fish, seafood and dairy products), followed by inhalation (both indoor and outdoor air), and, to a lesser extent, dust ingestion and dermal contact. Numerous studies reported the environmental and occupational exposure to these pollutants, deriving from building materials (flame-retardants, plasticizers, paints, caulking compounds, sealants, fluorescent light ballasts, etc.) and electrical equipment. The highest PCBs contaminations were detected in e-waste recycling sites, suggesting the need for the implementation of remediation strategies of such polluted areas to safeguard the health of workers and local populations. Furthermore, a significant correlation between PCB exposure and increased blood PCB concentrations was observed in people working in PCB-contaminated workplaces. Several epidemiological studies suggest that environmental and occupational exposure to high concentrations of PCBs is associated with different health outcomes, such as neuropsychological and neurobehavioral deficits, dementia, immune system dysfunctions, cardiovascular diseases and cancer. In addition, recent studies indicate that PCBs bioaccumulation can reduce fertility, with harmful effects on the reproductive system that can be passed to offspring. In the near future, further studies are needed to assess the real effects of PCBs exposure at low concentrations for prolonged exposure in workplaces and specific indoor environments

Real-Time US-CT fusion imaging for guidance of thermal ablation in of renal tumors invisible or poorly visible with US: results in 97 cases

Purpose To assess the capability of ultrasound-computed tomography (US-CT) fusion imaging to guide a precise targeting of renal tumors invisible or poorly visible with US Materials and methods From 2016 renal tumors poorly visible or inconspicuous/invisible at US were treated at our institution with the guidance of US/CT fusion in a room equipped with CT scanner. Feasibility of the procedure, accuracy of targeting, complications, and technique efficacy were evaluated. Results Of 227 patients treated from 2016 to March 2020, 91 patients (65 males and 26 females, mean age 68.5 ± 10.1 years) with 97 renal lesions (mean maximum diameter 21.6 ± 9.4 mm) inconspicuous/invisible (29/97, 29.9%) or poorly visible (68/97, 70.1%) at US underwent treatment under US-CT fusion guidance. US-CT fusion imaging guidance was always technically feasible and enabled correct targeting in 97/97/(100%) of cases. Technical success was achieved in 93/97 lesions (95.9%). Three lesions were retreated during the same ablative session, while 1 was retreated in a subsequent session. Thus, primary efficacy was achieved in one session in 96/97 (98.9%) cases and secondary efficacy in 97/97 (100%) cases Conclusion US-CT image fusion guidance allows for a correct tumor targeting of renal tumors poorly visible or inconspicuous/invisible with US alone, with a high rate of technical success and technique efficacy

New Cross-Talk Layer between Ultraconserved Non-Coding RNAs, MicroRNAs and Polycomb Protein YY1 in Bladder Cancer

MicroRNAs (miRNAs) are highly conserved elements in mammals, and exert key regulatory functions. Growing evidence shows that miRNAs can interact with another class of non-coding RNAs, so-called transcribed ultraconserved regions (T-UCRs), which take part in transcriptional, post-transcriptional and epigenetic regulation processes. We report here the interaction of miRNAs and T-UCRs as a network modulating the availability of these non-coding RNAs in bladder cancer cells. In our cell system, antagomiR-596 increased the expression of T-UCR 201+. Moreover, T-UCR 8+ silencing increased miR-596 expression, which in turn reduced total T-UCR 283+, showing that the perturbation of one element in this network changes the expression of other interactors. In addition, we identify the polycomb protein Yin Yang 1 (YY1) as mediator of binding between miR-596 and T-UCR 8+. These new findings describe for the first time a network between T-UCRs, miRNAs and YY1 protein, highlighting the existence of an additional layer of gene expression regulation