Antioxidant imbalance and genotoxicity detected in fish induced by titanium dioxide nanoparticles (NpTiO2) and inorganic lead (PbII)

Titanium dioxide nanoparticles (NpTiO₂) are the most widely-used nanoparticle type and the adsorption of metals such as lead (PbII) onto their surface is a major source of concern to scientists. This study evaluated the effects of the associated exposure to both types of contaminant, i.e., lead (a known genotoxic metal) and NpTiO₂, in a freshwater fish (Astyanax serratus) through intraperitoneal injection for an acute assay of 96 h. The effects of this exposure were evaluated using the comet assay, DNA diffusion assay and piscine micronucleus test, as well as the quantification of antioxidant enzymes (SOD, CAT, and GST) and metallothioneins. Our findings indicate that co-exposure of PbII with NpTiO₂ can provoke ROS imbalances, leading to DNA damage in the blood and liver tissue of A. serratus, as well as modifying erythropoiesis in this species, inducing necrosis and changing the nuclear morphology of the erythrocytes.     

Hygiene hypothesis and autoimmune diseases: A narrative review of clinical evidences and mechanisms

Since the start of the “modern era”, characterized by the increase in urbanization, a progressive attention to hygiene and autoimmune conditions has considerably grown. Although these diseases are often multifactorial, it was demonstrated that environment factors such as pollution, diet and lifestyles may play a crucial role together with genetic signature. Our research, based on the newest and most significant literature of this topic, highlights that the progressive depletion of microbes and parasites due to increased socioeconomic improvement, may lead to a derangement of immunoregulatory mechanisms. Moreover, special attention was given to the complex interplay between microbial agents, as gut microbiome, diet and vitamin D supplementation with the aim of identifying promising future therapeutic options. In conclusion, autoimmunity cannot be limited to hygiene-hypothesis, but from the point of view of precision medicine, this theory represents a fundamental element together with the study of genomics, the microbiome and proteomics, in order to understand the complex functioning of the immune system.     

Vaccination with Neospora caninum-cyclophilin and -profilin confers partial protection against experimental neosporosis-induced abortion in sheep

The purpose of this study was to evaluate the protective efficacy of a vaccine consisting of recombinant Neospora caninum-cyclophilin (NcCyP) and -profilin (NcPro) in sheep. At 42 d and 21 d prior to mating, adult Dorset ewes were immunized with the rNcCyP-rNcPro vaccine (Group 1) or co-purifying non-recombinant (NR) control vaccine (Group 2). At 90 days post-mating, all immunized ewes and were challenged by intravenous injection with 10⁶ Nesopora caninum Illinois tachyzoites (NcTZ). Significant protection (P < 0.05) was observed in Group 1 with 9 out of 13 ewes giving birth to live-born lambs (69.2%), whereas all Group 2 ewes aborted (6/6). Neospora caninum was detected by PCR in both fetal and placental tissues from all Group 2 aborting ewes and in the placental tissues of Group 1 aborting ewes. In contrast, tissues and placentas of Group 1 live-born lambs were Neospora DNA-negative. Immunoreactive Neospora antigens were demonstrated in placentas associated with abortions, but not in tissues of aborted fetuses or those of the live-born lambs and their associated placentas. Anti-NcCyP and anti-NcPro titers were high in sera from Group 1 ewes and were further boosted by challenge infection, resulting in long-lasting (≥14.5 mos.) elevated titers. Lambs born to Group 1 ewes also had high NcCyP and NcPro titers in pre-colostrum sera. Immunofluorescence staining (IFA) of NcTZ with Group 1 post-immunization sera revealed both surface and internal TZ staining, a pattern consistent with that observed with rabbit sera to rNcCyP or rNcPro. Infection of NR-vaccinated ewes produced high but transient anti-NcCyP and anti-NcPro Ab titers. The results indicate that the NcCyP-NcPro vaccine elicited strong anti-N. caninum responses and conferred significant protection against abortion and transplacental transmission of N. caninum TZ in sheep.     

Effects of peripheral tears of the triangular fibrocartilage complex on distal radioulnar joint stability: A biomechanical study

BackgroundPeripheral triangular fibrocartilage complex (TFCC) tears may induce instability of the distal radioulnar joint (DRUJ). In this biomechanical study, simulated peripheral tears of the TFCC were examined on the stability of the DRUJ. Restabilization effect of the DRUJ by ulnar shortening and direct repair of those injuries were sequentially examined.MethodThe DRUJ stiffness was measured in intact, simulated two types of peripheral tears (ulnar and extended ulnodorsal) at three forearm positions: neutral, 60° pronation and 60° supination in 8 fresh frozen cadaver specimens. After the tears were sutured with stitches or after simulated ulnar shortening of 3 mm, the DRUJ stiffness was again measured.ResultsThe ulnar and ulnodorsal TFCC tears decreased the DRUJ stiffness significantly compared with the intact in all forearm positions. When ulnar shortening was done for the ulnar tear, the DRUJ stiffness increased significantly in the neutral and 60° pronated positions. When the ulnar TFCC tear was repaired, the DRUJ stiffness increased significantly in all forearm positions. DRUJ stiffness did not increase either with ulnar shortening or repair in ulnodorsal tear of the TFCC, however.ConclusionThe simulated TFCC tears indicated significant loss of DRUJ stiffness. Direct repair or ulnar shortening was effective only on treatment of the ulnar tear of the TFCC in this study.     

Aspects of histocompatibility testing in xenotransplantation

Xenotransplantation, using genetically-modified pigs for clinical organ transplantation, is a solution to the organ shortage. The biggest barrier to clinical implementation is the antigenicity of pig cells. Humans possess preformed antibody to pig cells that initiate antibody-mediated rejection of pig organs in primates. Advances in genetic engineering have led to the development of a pig lacking the three known glycan xenoantigens (triple-knockout [TKO] pigs). A significant number of human sera demonstrate no antibody binding to TKO pig cells. As a result of the TKO pig's low antigen expression, survival of life-supporting pig organs in immunosuppressed nonhuman primates has significantly increased, and hope has been renewed for clinical trials of xenotransplantation.It is important to understand the context in which xenotransplantation's predecessor, allotransplantation, has been successful, and the steps needed for the success of xenotransplantation. Successful allotransplantation has been based on two main immunological approaches – (i) adequate immunosuppressive therapy, and (ii) careful histocompatibility matching. In vivo studies suggest that the available immunosuppressive regimens are adequate to suppress the human anti-pig cellular response. Methods to evaluate and screen patients for the first clinical xenotransplantation trial are the next challenge. The goal of this review is to summarize the history of histocompatibility testing, and the available tools that can be utilized to determine xenograft histocompatibility.     

Catabolic/Anabolic Imbalance Is Accompanied by Changes of Left Ventricular Steroid Nuclear Receptor Expression in Tachycardia-Induced Systolic Heart Failure in Male Pigs

BackgroundSteroid hormones play an important role in heart failure (HF) pathogenesis, and clinical data have revealed disordered steroidogenesis in male patients with HF. However, there is still a lack of studies on steroid hormones and their receptors during HF progression. Therefore, a porcine model of tachycardia-induced cardiomyopathy corresponding to HF was used to assess steroid hormone concentrations in serum and their nuclear receptor levels in heart tissue during the consecutive stages of HF.Methods and ResultsMale pigs underwent right ventricular pacing and developed a clinical picture of mild, moderate, or severe HF. Serum concentrations of dehydroepiandrosterone, testosterone, dihydrotestosterone, estradiol, aldosterone, and cortisol were assessed by enzyme-linked immunosorbent assay. Androgen receptor, estrogen receptor alpha, mineralocorticoid receptor, and glucocorticoid receptor messenger RNA levels in the left ventricle were determined by qPCR.The androgen level decreased in moderate and severe HF animals, while the corticosteroid level increased. The estradiol concentration remained stable. The quantitative real-time polymerase chain reaction revealed the downregulation of androgen receptor in consecutive stages of HF and increased expression of mineralocorticoid receptor messenger RNA under these conditions.ConclusionsIn the HF pig model, deteriorated catabolic/anabolic balance, manifested by upregulation of aldosterone and cortisol and downregulation of androgen signaling on the ligand level, was augmented by changes in steroid hormone receptor expression in the heart tissue.     

A Voltage-Sensitive Ultrasound Enhancing Agent for Myocardial Perfusion Imaging in a Rat Model

Echocardiographers with specialized expertise sometimes perform myocardial perfusion imaging using U.S. Food and Drug Administration-approved microbubbles in an off-label capacity, correlating microbubble replenishment in the near field with blood flow through the myocardium. This study reports the in vivo clinical feasibility of a voltage-sensitive ultrasound enhancing agent (UEA) for myocardial perfusion imaging. Four UEAs were injected into Sprague-Dawley rats while ultrasound images were collected to quantify brightness in the left ventricular (LV) cavity, septal wall, and posterior wall in systole and diastole. Formulation IV, a phase change agent nested within a negatively charged phospholipid bilayer, increased the tissue-to-cavity ratio in both systole and diastole in the septal wall, 6 dB, and in the posterior wall, 5 dB, while leaving the LV cavity at baseline. This outcome improves the signal of the myocardium relative to the LV cavity and shows promise as a myocardial perfusion UEA.     

Establishing a national biobank. Biobanking infrastructure initiative in Slovakia - Public policy,legal and ethical issues

Resulting from a multi-stakeholder initiative in 2017, a rapid process is underway in Slovakia with the aim of establishing a national system of biobanks by 2020. A combined top-down and bottom-up approach is being followed under the leadership of the Ministry of Health Institute for Research and Development. Relevant national stakeholders, with international expert partner institutions providing additional know how and networking, have been successfully involved since the very beginning of this initiative. State-of-the-art biobanking facilities are to be built in order to accommodate the Slovak National Biobank in the city of Martin (Central Slovakia) and the other major biobank in the city of Košice (Eastern Slovakia), while existing structures – future local biobanks – will be upgraded to achieve complete technical and logistical compatibility. This should enable full compliance of the Slovakia's biobanking system with the appropriate international ethical, legal and professional standards. A related legislative activity has been started, aimed at a comprehensive updating of the existing Slovak biomedical research and health care legislation, to provide for the necessary legal certainty. After successful completion of the Initiative, the Slovakia's biomedical research infrastructure is to be better set for supporting excellent domestic research and development efforts, as well as for its involvement in high-quality international research collaborations and partnerships.