Are elevated mitochondrial DNA fragments in prostatic inflammation a potential biomarker for prostate cancer?

Background: We sought to determine whether two soluble forms with different size of mtDNA are linked to prostatic inflammation, and whether they discriminate prostate cancer (PCa) from inflammatory prostatic conditions. Methods: Histopathologically diagnosed prostatitis, PCa and benign prostatic hyperplasia patients (n = 93) were enrolled in this study and they were categorized as with and without prostate inflammation. Quantitative RT-PCR was used to analyze the levels of 79-bp and 230-bp fragments in urine and blood samples collected following prostate massage. Results: The urine mtDNA-79 and mtDNA-230 were significantly increased in patients with prostate inflammation compared with those in without inflammation. Here, 79-bp fragment of apoptotic origin was significantly higher level than 230-bp fragment of necrotic origin. Although mtDNA-79 copy number in serum samples was also increased in patients with prostate inflammation, mtDNA-230 was similar in the two groups. Furthermore, mtDNA-79 and mtDNA-230 copy numbers in postprostate massage urine were higher (about 16-fold and 22-fold, respectively) than those from serum samples. ROC analysis showed that, although post-prostate massage urine have relatively higher performance than blood, ability to discriminate cases of both fragments was not better than that of serum total PSA. Conclusions: Our results demonstrate that shorter cf-mtDNA fragment size in particular, increase in the presence of prostate inflammation in post-prostatic massage urine but both fragments could never improve serum total PSA performance

Monitoring of platelet function parameters and microRNA expression levels in patients with prostate cancer treated with volumetric modulated arc radiotherapy

Radiotherapy (RT) may result in platelet activation and thrombosis development. To the best of our knowledge, the potential effect of volumetric-modulated arc therapy (VMAT), a novel radiotherapy technique, on platelet function and microRNA (miRNA/miR) expression has not been previously investigated. The present study aimed to determine the effect of VMAT on the alterations in platelet function parameters and miRNA expression levels. A total of 25 patients with prostate cancer and 25 healthy subjects were included in the present study. Blood samples were collected from the patient group on the day prior to RT (pre-RT), the day RT was completed (post-RT day 0), and 40 days following the end of therapy (post-RT day 40). Platelet count, mean platelet volume (MPV) value, platelet aggregation, plasma P-selectin, thrombospondin-1, platelet factor 4, plasma miR-223 and miR-126 expression levels were measured. A significant decrease in platelet count in the post-RT day 0 group was measured in comparison with the pre-RT and the post-RT day 40 groups. Pre-RT MPV values were higher than those of the post-RT day 0 and the post-RT day 40 groups. No significant differences were observed in the levels of platelet activation markers or miR-223 and miR-126 expression levels between the RT groups. Although RT may result in a reduction in platelet and MPV counts, the results of the present study indicate that platelet activation markers are not affected by VMAT. Therefore, it is possible that no platelet activation occurs during VMAT, owing to the conformal dose distributions, improved target volume coverage and the sparing of normal tissues from undesired radiation

Investigation of renal and testicular pro-inflammatory cytokine levels in experimental hyperthyroidism: Effects of selenium supplementation

Cytokines play important roles in diseases. Pro-inflammatory cytokines may responsible for thyroid dysfunction. Selenium (Se) regulates pro-inflammatory status in the body. Kidney and testicular functions change in hyperthyroidism. The aim of this study was to investigate the effects of Se supplementation on pro-inflammatory cytokines in renal and testicular tissue in hyperthyroid rats. This study was carried out with 6 experimental groups (G). G-1 consisted of controls receiving standard rat fodder. Other experimental groups were fed with; G-2: 0.5 mg/kg Na2SeO3; G-3: 1 mg/kg Na2SeO3; G-4: 4 mg/kg L-thyroxine; G-5: 0.5 mg/kg Na2SeO3 and 4 mg/kg L-thyroxine; G-6: 1 mg/kg Na2SeO3 and 4 mg/kg L-thyroxine added standard fodder. Interleukin (IL)-1β, IL-6, IL-18, and TNF-α levels were studied in renal and testicular tissues by ELISA. All cytokines levels of kidney samples were measured in tissue homogenates. Kidney values of IL-1β, IL-18, IL-6 and TNF-α were increased in G-4 compared to G-1 (p=0.024, p=0.010, p=0.003, and p=0.011, respectively). Also, these cytokine levels were decreased in G-6 compared to G-4 (p=0.042, p=0.048, p=0.009, and p=0.021, respectively). The IL-1β, IL-18, IL-6 and TNF-α values of G-4 were higher than G-1 in testes samples (p=0.027, p=0.010, p=0.008, and p=0.009, respectively). In addition, G-6 levels of IL-18 and TNF-α were lower than G-4 (p=0.047, and p=0.032 respectively), but IL-1β and IL-6 changes were not significant. As a result, our findings showed that in hyperthyroidism IL-1β, IL-18, IL-6, and TNF-α levels increased in kidney and testis tissues. Also, supplementation of 1 mg/kg Na2SeO3 was more effective for decreasing levels of these pro-inflammatory cytokine levels in the hyperthyroid group. [Med-Science 2020; 9(2.000): 393-8

Antioxidant and Anti-Inflammatory Effects of Nicotinamide Adenine Dinucleotide (NAD(+)) Against Acute Hepatorenal Oxidative Injury in An Experimental Sepsis Model

The aim of this study is to determine the antioxidant and anti-inflammatory effects of Nicotinamide Adenine Dinucleotide (NAD+) in preventing multi-organ damage caused by sepsis. Twenty-eight male Wistar-albino rats were randomly divided into four groups. The study groups comprised Sham group, sepsis group (CLP), sepsis + 100 mg/kg NAD+ (CLP+N100) and sepsis + 300 mg/kg NAD+ group (CLP+N300). Sepsis was induced by the cecum ligation perforation (CLP) method. NAD+ was administered intraperitoneally for five days before cecum perforation and 6 h after operation. Serum, liver and kidney tissues were taken from the rats 24 h after the operation. MDA, GSH, CAT, TNF-alpha, IL-6, IL-1 beta, and caspase-3 parameters were measured in tissue samples with biochemical and immunohistochemical methods. In the histopathological and immunohistochemical examination, increases in TNF-alpha, IL-6, IL-1 beta, and caspase-3 expressions were observed in the liver and kidney tissues of the CLP group and severe damage was seen in tissue morphology (P<0.001). Hepatorenal injury was significantly decreased in the treatment groups. Sepsis increased MDA levels in all tissues, but significantly decreased GSH and CAT activities. While NAD+ administration significantly increased GSH and CAT activity in the liver and kidney tissues, it caused a significant decrease in MDA levels. This study shows that nicotinamide may be a potent therapeutic agent for the treatment of sepsis