Inflammatory cytokine levels and changes during omalizumab treatment in chronic spontaneous urticaria.

While several studies have examined the role of T cells and related cytokines in the development of chronic spontaneous urticaria (CSU), there is a limited amount of research focusing on the changes in cytokine levels during omalizumab treatment. The primary objective of this study was to investigate the inflammatory cytokine profile (including IL-4, IL-5, IL-10, IL-13, IL-17, IL-31, IL-33, and TNFα) among CSU patients undergoing to omalizumab treatment. Plasma levels of cytokines were measured using ELISA. Measurements were taken before CSU treatment, at the 3rd and 6th months of omalizumab treatment, and once in the control group. The severity of the patients' disease was assessed using the weekly Urticaria Activity Score(UAS7), and disease control was evaluated using the Urticaria Control Test(UCT). Thirty-one CSU patients and 56 age- and gender-matched healthy controls were included. Plasma levels of IL-4 and IL-33 were significantly lower in patients with CSU compared to healthy controls (p = 0.001; p = 0.038, respectively). During omalizumab treatment, IL-4 levels showed a significant increase in the 3rd month compared to baseline (p = 0.01), and IL-5 levels significantly decreased in the 6th month compared to both the 3rd month and baseline (6th month vs. baseline; p = 0.006, 6th month vs. 3rd month; p = 0.001). One potential mechanism of action for omalizumab may involve its regulatory effects on type 2 inflammatory cytokines in CSU patients. This finding partially explains the efficacy of anti-IL-4/13 treatments in chronic spontaneous urticaria. Further investigations on drugs targeting type 2 inflammatory cytokines in CSU are warranted.

Presence of fetal DNA in maternal exhaled breath condensate.

OBJECTIVES: Cell-free DNA has been found in all body fluids, but DNAs emerging from locations that are not in direct contact with breath in exhaled breath condensate (EBC) are yet to be found. The potential of EBC for prenatal and cancer screening prompted us to investigate whether fetal DNA is present in maternal EBC. METHOD: A total of 20 pregnant women's EBC and blood samples were collected. Four Y chromosome-specific assays were tested on all EBC and plasma samples by quantitative PCR (qPCR). The best-performing assay was used for digital droplet PCR (ddPCR) on all EBC and the six plasma samples. RESULTS: The sex of the fetuses was accurately determined from plasma samples. DNA sequences could not be properly amplified in EBC samples by the qPCR. By ddPCR, the Y chromosome sequence was amplified in two of the 11 EBC samples, from women carrying male fetuses (2/11), and the Y chromosome sequence was not amplified in the EBC of women carrying female fetuses (9/9). Exhaled breath condensate ddPCR result's specificity was 100%, the detection rate of Y chromosome was 18.18% (2/11), and the corrected accuracy was 59.09%. CONCLUSION: Our finding of "the presence of fetal DNA in maternal EBC", despite the low detection rate, might have a major impact on prenatal diagnosis and cancer screening.

Neuroprotective Effect of Plasminogen Activator Inhibitor-1 Antagonist in the Rat Model of Mild Traumatic Brain Injury.

Plasminogen activator inhibitor-1 (PAI-1) antagonists are known for their neuroprotective effects. In this study, it was aimed to investigate the possible protective effects of PAI-1 antagonists in a rat mild traumatic brain injury (TBI) model. Sprague-Dawley male rats were grouped as sham (n = 7), TBI (n = 9), and TBI + PAI-1 antagonist (5 and 10 mg/kg TM5441 and TM5484; n = 6-7). Under anesthesia, TBI was induced by dropping a metal 300-g weight from a height of 1 m on the skull. Before and 24-h after trauma neurological examination, tail suspension, Y-maze, and novel object recognition tests were performed. Twenty-four hours after TBI, the rats were decapitated and activities of myeloperoxidase, nitric oxide release, luminol-, and lucigenin-enhanced chemiluminescence were measured. Also, interleukin-1ß, interleukin-6, tumor necrosis factor, interleukin-10, tumor growth factor-ß, caspase-3, cleaved caspase-3, and PAI levels were measured with the ELISA method in the brain tissue. Brain injury was graded histopathologically following hematoxylin-eosin staining. Western blot and immunohistochemical investigation for low-density lipoprotein receptor, matrix metalloproteinase-3, and nuclear factor-κB were also performed. Data were analyzed using GraphPad Prism 8.0 (GraphPad Software, San Diego, CA, USA) and expressed as means ± SEM. Values of p < 0.05 were considered to be statistically significant. Higher levels of myeloperoxidase activity in the TBI group (p < 0.05) were found to be suppressed in 5 and 10 mg/kg TM5441 treatment groups (p < 0.05-p < 0.01). The tail suspension test score was increased in the TBI group (p < 0.001) and decreased in all treatment groups (p < 0.05-0.001). The histologic damage score was increased statistically significantly in the cortex, dentate gyrus, and CA3 regions in the TBI group (p < 0.01-0.001), decreased in the treatment groups in the cortex and dentate gyrus (p < 0.05-0.001). PAI antagonists, especially TM5441, have antioxidant and anti-inflammatory properties against mild TBI in the acute period. Behavioral test results were also improved after PAI antagonist treatment after mild TBI.

Analyses of Copy Number Variations in Myxopapillary Ependymomas of Cauda Equina.

AIM: To identify the copy number variations that are specific to myxopapillary ependymomas (MPEs) of the cauda equina. MATERIAL AND METHODS: The patient cohort included five patients who underwent resection of histologically confirmed MPEs. Tumor samples collected during surgery and stored in liquid nitrogen as well as corresponding blood samples collected were analyzed. Genomic DNA from the venous blood and tumor samples was obtained using standard techniques and hybridized to a Cytoscan 750K Array in accordance with the manufacturer’s introductions. RESULTS: As a novel finding, amplification on chromosome 14q32.33 was detected in all tumor and blood samples, except one tumor sample. All tumor tissues also showed amplification on chromosomes 5, 7, 9, and 16. CONCLUSION: Although further studies with larger cohorts are required to identify genes involved in MPE tumorigenesis and to validate our results, these findings provide a basis for advanced molecular biological and genetic studies of MPEs.

New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins.

Bladder cancer is the 10th-most common cancer worldwide. The diagnosis and follow-up of patients require costly invasive methods and due to these expenses, bladder cancer continues to be one of the expensive malignancies. Early diagnosis is crucial in bladder cancer as it is in other cancers; therefore, non-invasive biomarkers for early diagnosis are very important. In this review, we aimed to focus on the most recent investigations on potential urinary micro RNA (miRNA) and protein biomarkers for bladder cancer diagnosis and their associated pathways. Studies performed by different groups were compiled and the biomarker properties of various proteins and miRNAs in the urine of bladder cancer patients were evaluated. Key studies were obtained by searching keywords "bladder cancer, urinary miRNA, urinary protein, urinary biomarker". Targets and the pathways of the miRNAs and proteins were analyzed according to mirBase Catalogue and Panther Database. The major pathways that are targeted by aberrantly expressed miRNAs are Cholecystokinin receptor (CCKR), p53, Wnt signaling pathway, and feedback loops. We hereby conclude that urinary micro RNAs and proteins are promising candidates for bladder cancer diagnosis. It should be noted that urine collection, storage conditions, choice of fraction, and normalization strategies should be standardized.