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Abstract Background Central arterial stiffness represents a well-established predictor of cardiovascular disease. Decreased circulating endothelial progenitor cells (EPCs), increased asymmetric dimethyl-arginine (ADMA) levels, traditional cardiovascular risk factors and insulin resistance have all been associated with increased arterial stiffness. The correlations of novel and traditional cardiovascular risk factors with central arterial stiffness in prediabetic individuals were investigated in the present study. Methods The study population consisted of 53 prediabetic individuals. Individuals were divided into groups of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IGT-IFG. Age, sex, family history of diabetes, smoking history, body mass index (BMI), waist to hip ratio (WHR), waist circumference (WC), blood pressure, lipid profile, levels of high sensitive C-reactive protein (hsCRP), glomerular filtration rate (GFR), and history of antihypertensive or statin therapy were obtained from all participants. Insulin resistance was evaluated using the Homeostatic Model Assessment (HOMA-IR). Carotid -femoral pulse wave velocity was used as an index of arterial stiffness. Circulating EPC count and ADMA serum levels were also determined. Results Among studied individuals 30 (56.6%) subjects were diagnosed with isolated IFG, 9 (17%) with isolated IGT (17%) and 14 with combined IFG-IGT (26.4%). In univariate analysis age, mean blood pressure, fasting glucose, total cholesterol, LDL cholesterol, and ADMA levels positively correlated with pulse-wave velocity while exercise and GFR correlated negatively. EPC count did not correlate with PWV. In multivariate stepwise regression analysis PWV correlated independently and positively with LDL-Cholesterol (low density lipoprotein) and ADMA levels and negatively with exercise. Conclusions Elevated ADMA and LDL-C levels are strongly associated with increased arterial stiffness among pre-diabetic subjects. In contrast exercise inversely correlated with arterial stiffness.

Background: Various studies have reported associations between frequencies of total peripheral blood lymphocytes and prostate cancer prognosis, but none so far has addressed the prognostic role of CD8+ T-lymphocyte subsets. Methods: A total of 43 prostate cancer patients with metastatic disease and 81 patients with non-metastatic disease were included in this study. Flow cytometry analyses were employed for determining the frequencies of peripheral CD8+ T-lymphocyte subsets. Results: Statistically significant lower levels of terminally differentiated effector (TEMRA) cells in patients with non-metastatic disease vs. patients with metastatic disease were observed. Central memory (CM) and effector memory (EM) CD8+ subsets, were found to be significantly higher in patients with non-metastatic disease vs. patients with metastatic disease. A similar profile was revealed when these CD8+ subsets were analyzed based on the patients’ Gleason scores, as well as by combined disease stage (i.e., non-metastatic vs. metastatic disease) and Gleason score. Conclusions: Peripheral blood-derived CD8+ T-lymphocyte memory subsets could function as biomarkers for the prognosis of PCa.

A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure–activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as “synthetic nucleases”, independently of oxygen and pH. Calf thymus–DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating DNA-photocleavers, and are proposed as new leads for “on demand” biotechnological applications in drug discovery and medicine.

Semen hyperviscosity impairs sperm motility and can lead to male infertility. This prospective study aimed at assessing the ability of exogenous DNase in improving sperm quality, taking into consideration that DNase has been found in the seminal plasma of several species and that neutrophils release chromatin in order to trap bacteria. A total of seventy-seven semen samples with high seminal viscosity (HSV) as the study group and sixty-two semen samples with normal seminal viscosity (NSV) as the control group were compared in this analysis. These semen samples were divided into three groups of receiving treatment (a) with DNase I at 37°C for 15 min, (b) by density gradient centrifugation, and (c) with a combination of the above two methods. Following a fifteen-minute treatment of hyperviscous semen, the motility of spermatozoa in 83% of semen samples increased to a statistically significant degree. On the contrary, DNase treatment of semen with normal viscosity had no such effects. The above treatment was also accompanied by a significant increase in the percentage of normal spermatozoa, resulting in a major decrease of the teratozoospermia index. Comparison between semen samples that underwent density gradient centrifugation following DNase I treatment, to those collected after density gradient treatment alone, showed that in the first case the results were more spectacular. The evaluation of each preparation in terms of yield (% total progressively motile sperm count after treatment in relation to the initial total sperm count) revealed that the combined approach resulted in 29.8% vs. 18.5% with density treatment alone (p=0.0121). DNase I treatment results in an improvement of sperm motility and morphology and could be beneficial to men with hyperviscous semen in assisted reproduction protocols.

Simple Summary: The field of precision oncology may benefit from the discovery of reliable biomarkers for prognosis and prediction, which will help to tailor therapeutic treatments, thus avoiding overdosing, over-treatment and side effects. Such biomarkers are usually discovered in the tumor tissue, which is not an easy task given the inaccessibility of the malignant tissue in many types of cancer. In contrast, liquid biopsies, by being non-invasive procedures, can be repeatedly obtained from patients without any discomfort during their therapy, thus conferring an important advantage over tissue biopsy analysis. In this work, we could identify, for the first time, a prognostic biosignature consisting of CD8+ T-lymphocyte subsets in the peripheral blood of prostate cancer patients. Background: Various studies have reported associations between frequencies of total peripheral blood lymphocytes and prostate cancer prognosis, but none so far has addressed the prognostic role of CD8+ T-lymphocyte subsets. Methods: A total of 43 prostate cancer patients with metastatic disease and 81 patients with non-metastatic disease were included in this study. Flow cytometry analyses were employed for determining the frequencies of peripheral CD8+ T-lymphocyte subsets. Results: Statistically significant lower levels of terminally differentiated effector (TEMRA) cells in patients with non-metastatic disease vs. patients with metastatic disease were observed. Central memory (CM) and effector memory (EM) CD8+ subsets, were found to be significantly higher in patients with non-metastatic disease vs. patients with metastatic disease. A similar profile was revealed when these CD8+ subsets were analyzed based on the patients' Gleason scores, as well as by combined disease stage (i.e., non-metastatic vs. metastatic disease) and Gleason score. Conclusions: Peripheral blood-derived CD8+ T-lymphocyte memory subsets could function as biomarkers for the prognosis of PCa. [ABSTRACT FROM AUTHOR]

HER-2/neu is the human epidermal growth factor receptor 2, which is associated with the progression of prostate cancer (PCa). HER-2/neu-specific T cell immunity has been shown to predict immunologic and clinical responses in PCa patients treated with HER-2/neu peptide vaccines. However, its prognostic role in PCa patients receiving conventional treatment is unknown, and this was addressed in this study. The densities of CD8+ T cells specific for the HER-2/neu(780–788) peptide in the peripheral blood of PCa patients under standard treatments were correlated with TGF-β/IL-8 levels and clinical outcomes. We demonstrated that PCa patients with high frequencies of HER-2/neu(780–788)-specific CD8+ T lymphocytes had better progression-free survival (PFS) as compared with PCa patients with low frequencies. Increased frequencies of HER-2/neu(780–788)-specific CD8+ T lymphocytes were also associated with lower levels of TGF-β and IL-8. Our data provide the first evidence of the predictive role of HER-2/neu-specific T cell immunity in PCa. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation therapy (RT) is an established therapeutic regimen for prostate cancer patients which aims for the direct elimination of tumor cells in the prostate gland and occasionally at distant anatomic sites. In this study, we performed next-generation sequencing-based gene expression analysis in peripheral blood from prostate cancer patients obtained pre- and post-radiotherapy and found six independently down-regulated genes including CCR7, FCGR2B, BTLA, CD6, CD3D, and CD3E. The analysis of the expression of the 6-genes as a signature also revealed significantly lower levels post- vs. pre-radiotherapy. Data extracted from the PRAD (PRostate ADenocarcinomas) dataset linked low levels of the 6-gene signature to better survival. More importantly, this 6-gene signature strongly correlated with a favorable prognosis regardless of poor standard clinicopathological parameters (i.e., Gleason score ≥ 8 and T3), thus highlighting its potential predictive value. Radiotherapy for localized prostate cancer has increased the cure and survival rates of patients. Besides its local tumoricidal effects, ionizing radiation has been linked to mechanisms leading to systemic immune activation, a phenomenon called the abscopal effect. In this study, we performed gene expression analysis on peripheral blood from prostate cancer patients obtained post- radiotherapy and showed that 6 genes, including CCR7, FCGR2B, BTLA, CD6, CD3D, and CD3E, were down-regulated by a range of 1.5–2.5-fold as compared to pre-radiotherapy samples. The expression of the signature consisting of these six genes was also significantly lower post- vs. pre-radiotherapy. These genes are involved in various tumor-promoting immune pathways and their down-regulation post-radiotherapy could be considered beneficial for patients. This is supported by the fact that low mRNA expression levels for the 6-gene signature in the prostate tumor tissue was linked to better survival. Importantly, we report that this 6-gene signature strongly correlated with a favorable prognosis regardless of poor standard clinicopathological parameters (i.e., Gleason score ≥ 8 and T3 (including T3a and T3b). Our pioneering data open the possibility that the 6-gene signature identified herein may have a predictive value, but this requires further long-term studies. [ABSTRACT FROM AUTHOR]