Effect of Epidermal Growth Factor (EGF) on Cryopreserved Piedmontese Bull Semen Characteristics

SIMPLE SUMMARY: This study aimed to investigate bull thawed semen characteristics under the effect of different concentrations (0, 50, 100, 200, and 400 ng/mL) of EGF being added to the extender prior to freezing. Semen samples collected from four bulls for 8 weeks were pooled, diluted with Bullxcell(®) extender supplemented with EGF at different concentrations, cooled, and frozen. After thawing, semen was examined for different parameters, including motility, kinetics, vitality, integrity, mitochondrial and antioxidant (SOD) activities, mucus penetration distance, as well as in vitro fertilizing capability. EGF incorporation in semen extender improved the total, progressive, and rapid motility and the sperm velocity at 50, 200, and 400 ng/mL after different incubation periods (from 1 to 4 h). We conclude that EGF supplementation to bull sperm extender before cryopreservation has an improving effect on sperm motility and kinetics without affecting sperm parameters. ABSTRACT: The purpose of this study was to determine the effect on fresh and post-thaw beef bull semen quality of the supplementation of epidermal growth factor (EGF) to the semen extender at various concentrations (0-control, 50, 100, 200, and 400 ng/mL). For 8 weeks, sperm was collected from four fertile bulls, yielding a total of 32 ejaculates. Semen samples were pooled, diluted with Bullxcell(®) extender, and then cooled, equilibrated, and frozen. After thawing, semen was tested for motility and velocity parameters. Furthermore, semen was evaluated for vitality, integrity, mitochondrial and antioxidant (SOD) activities, mucus penetration distance, and in vitro fertilizing capability. The supplementation with EGF prior to cryopreservation improved the total sperm motility at various concentrations over long incubation periods (from 1 to 4 h). Interestingly, EGF addition improved both progressive and rapid motility, particularly at 50, 200, and 400 ng/mL. In addition, EGF, primarily at 200 and 400 ng/mL, significantly increased several velocity parameters after different incubation periods. We can conclude that adding EGF to bull sperm extender before cryopreservation has a positive stimulatory effect on sperm motility without affecting vitality, integrity, or in vitro fertilizing capability

Estimating diagnostic accuracy of tests for latent tuberculosis infection without a gold standard among healthcare workers

Binary file ES_Abstracts_Final_ECDC.txt matche

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a “signature pathway” associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets

: Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible

Accuracy of Immunodiagnostic Tests for Active Tuberculosis Using Single and Combined Results: A Multicenter TBNET-Study

The clinical application of IFN-gamma release assays (IGRAs) has recently improved the diagnosis of latent tuberculosis infection. In a multicenter study of the Tuberculosis Network European Trialsgroup (TBNET) we aimed to ascertain in routine clinical practice the accuracy of a novel assay using selected peptides encoded in the mycobacterial genomic region of difference (RD) 1 for the diagnosis of active tuberculosis in comparison with tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (Cellestis Ltd., Carnegie, Australia) and T-SPOT.TB (Oxfordimmunotec, Abingdon, UK)

Distribution of misfolded prion protein seeding activity alone does not predict regions of neurodegeneration

Protein misfolding is common across many neurodegenerative diseases, with misfolded proteins acting as seeds for "prion-like" conversion of normally folded protein to abnormal conformations. A central hypothesis is that misfolded protein accumulation, spread and distribution is restricted to specific neuronal populations of the central nervous system and thus predict regions of neurodegeneration. We examined this hypothesis using a highly sensitive assay system for detection of misfolded protein seeds in a murine model of prion disease. Misfolded prion protein seeds were observed widespread throughout the brain accumulating in all brain regions examined irrespective of neurodegeneration. Importantly neither time of exposure nor amount of misfolded protein seeds present determined regions of neurodegeneration. We further demonstrate two distinct microglia responses in prion infected brains, a 11 novel homeostatic response in all regions and an innate immune response restricted to sites of 12 neurodegeneration. Therefore accumulation of misfolded prion protein alone does not define targeting 13 of neurodegeneration which instead results only when misfolded prion protein accompanies a specific 14 innate immune response

Signalling mechanisms mediating Zn2+-induced TRPM2 channel activation and death cell in microglial cells

Excessive Zn2+ causes brain damage via promoting ROS generation. Here we investigated the role of ROS-sensitive TRPM2 channel in H2O2/Zn2+-induced Ca2+ signalling and cell death in microglial cells. H2O2/Zn2+ induced concentration-dependent increases in cytosolic Ca2+ concentration ([Ca2+]c), which was inhibited by PJ34, a PARP inhibitor, and abolished by TRPM2 knockout (TRPM2-KO). Pathological concentrations of H2O2/Zn2+ induced substantial cell death that was inhibited by PJ34 and DPQ, PARP inhibitors, 2-APB, a TRPM2 channel inhibitor, and prevented by TRPM2-KO. Further analysis indicate that Zn2+ induced ROS production, PARP-1 stimulation, increase in the [Ca2+]c and cell death, which were suppressed by chelerythrine, a protein kinase C inhibitor, DPI, a NADPH-dependent oxidase (NOX) inhibitor, GKT137831, a NOX1/4 inhibitor, and Phox-I2, a NOX2 inhibitor. Furthermore, Zn2+-induced PARP-1 stimulation, increase in the [Ca2+]c and cell death were inhibited by PF431396, a Ca2+-sensitive PYK2 inhibitor, and U0126, a MEK/ERK inhibitor. Taken together, our study shows PKC/NOX-mediated ROS generation and PARP-1 activation as an important mechanism in Zn2+-induced TRPM2 channel activation and, TRPM2-mediated increase in the [Ca2+]c to trigger the PYK2/MEK/ERK signalling pathway as a positive feedback mechanism that amplifies the TRPM2 channel activation. Activation of these TRPM2-depenent signalling mechanisms ultimately drives Zn2+-induced Ca2+ overloading and cell death