Vitamin C modulates DNA damage induced by hydrogen peroxide in human colorectal adenocarcinoma cell lines (HT29) estimated by comet assay in vitro

Introduction

Cancer cells, compared to normal cells, are under increased oxidative stress associated with oncogenic transformation, alterations in metabolic activity, and increased generation of reactive oxygen species.

Material and methods

We investigated the ability of vitamin C to reduce the damage induced by hydrogen peroxide, in human colorectal adenocarcinoma cells in vitro by the comet assay. Additionally, we measured the kinetics and efficacy of the repair of DNA damage after incubation with vitamin C in the presence of H₂O₂.

Results

The obtained results showed that 1 h pre-incubation with vitamin C and exposure to H₂O₂ for the last 10 min of incubation caused a statistically significant (p < 0.05) increase in DNA migration in comet tails in all experimental series. For the 10 µM, 25 µM, 50 µM, 100 µM vitamin C concentrations the levels of DNA damage were as follows: 18.6%, 21.1%, 25.3% and 27.2%, respectively, as compared to the untreated cells (3.26%). However, in comparison with H₂O₂ alone (29.1%), we observed a statistically significant (p < 0.05) decrease of the genotoxic effect in HT29 cells induced by H₂O₂ for the two lowest of concentrations of vitamin C: 10 µM and 25 µM. The HT29 cells were able to achieve effective repair of the damaged DNA within 60 and 120 min after incubation with the tested compounds. All the values obtained in the test were statistically significant (p < 0.05).

Conclusions

Vitamin C caused a weaker DNA damaging effect of hydrogen peroxide and positively influences the level of oxidative DNA damage in HT29 cells (decrease ∼ 30%). We noted that DNA damage was effectively repaired during 120 min postincubation in the tested cells and that oxidative damage was the major type of damage.     

Brain structure in asymptomatic FMR1 premutation carriers at risk for fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.     

The function of type I interferons in antimicrobial immunity

Type I interferons (IFN-alpha and IFN-beta) were originally described as potent antiviral substances, which are produced upon infection of animal cells with viruses. Despite a large body of literature that has accumulated during the past 25 years, their regulatory function in the immune system is still much less appreciated. Recent studies have highlighted the production of type I IFNs, their function in the immune response to infectious agents and the target cells of these interferons. Type I IFNs clearly affect the release of proinflammatory cytokines or nitric oxide by dendritic cells and macrophages, the capacity of type II interferon (IFN-gamma) to activate phagocytes, the differentiation of T helper cells and the innate control of non-viral pathogens.     

Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections

European Journal of Clinical Microbiology & Infectious Diseases - SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly...     

Correction to: Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections

European Journal of Clinical Microbiology & Infectious Diseases -     

Prognostic markers in pT3 bladder cancer: A study from the international bladder cancer tissue microarray project

PurposeWe evaluated the prognostic value of 10 putative tumor markers by immunohistochemistry in a large multi-institutional cohort of patients with locally advanced urothelial cancer of the bladder (UCB) with the aim to validate their clinical value and to harmonize protocols for their evaluation.Materials and MethodsPrimary tumor specimens from 576 patients with pathologic (p)T3 UCB were collected from 24 institutions in North America and Europe. Three replicate 0.6-mm core diameter samples were collected for the construction of a tissue microarray (TMA). Immunohistochemistry (IHC) for 10 previously described tumor markers was performed and scored at 3 laboratories independently according to a standardized protocol. Associations between marker positivity and freedom from recurrence (FFR) or overall survival (OS) were analyzed separately for each individual laboratory using Cox regression analysis.ResultsThe overall agreement of the IHC scoring among laboratories was poor. Correlation among the 3 laboratories varied across the 10 markers. There was generally a lack of association between the individual markers and FFR or OS. The number of altered cell cycle regulators (p53, Rb, and p21) was associated with increased risk of cancer recurrence (P < 0.032). There was no clear pattern in the relationship between the percentage of markers altered in an 8-marker panel and FFR or OS.ConclusionsThis large international TMA of locally advanced (pT3) UCB suggests that altered expression of p53, Rb, and p21 is associated with worse outcome. However this study also highlights limitations in the reproducibility of IHC even in the most expert hands.     

Clinical Significance of Gastrointestinal Carriage of Klebsiella Pneumoniae-Producing Extended-Spectrum Beta-Lactamases in Kidney Graft Recipients

The burden of Klebsiella pneumoniae (KP) producing extended-spectrum beta-lactamases (ESBL+) urinary tract infections (UTIs) is a growing problem after kidney transplantation (KTX). The study was aimed at evaluating the incidence of KP ESBL+ gut colonization in KTX recipients and its correlation with clinical outcomes with special regard to UTIs.The study included all KTX patients hospitalized in our department between January 2014 and December 2016. During this period 2018 KTX patients were admitted: 605 in 2014, 750 in 2015, and 663 in 2016, respectively. Screening for drug-multiresistant Enterobacteriaceae gut carriage was performed in 104 patients (2014), 122 (2015), and 166 (2016).In 2014, 2015, and 2016, 18 (17.3%), 26 (21.3%), and 30 (18.1%) patients had positive test results, and 44 (42.3%), 36 (29.5%), and 45 (27.4%) KTX patients were diagnosed with KP ESBL+ UTI. In 2014, KP ESBL+ UTI was diagnosed in 30 (34.9%) cases with negative anal swab and in 14 patients (77.8%) with positive test result (P = .0008). In 2015, KP ESBL+ UTI was diagnosed in 21 patients (21.9%) with negative anal swab and in 15 (57.7%) with positive test result (P = .0004). In 2016, KP ESBL+ UTI was diagnosed in 24 patients (17.8%) with negative anal swab and in 21 (72.4%) with positive test result (P = .000001).In conclusion, we have revealed a strong association between gut K. pneumoniae colonization, female sex, and MPA intake and KP ESBL+ urinary tract infections in kidney transplant recipients. Our results indicate the very important role of KP ESBL+ screening, while strategies of identified carriers require further research.     

Body size and food size in freshwater zooplankton

We used double-label liquid scintillation techniques to measure the efficiencies with which eight different-sized zooplankton species ingested four cell types relative to a standard cell type (Chlamydomonas). Efficiency ratios (ERs: clearance rate on cell type X ÷ clearance rate on Chlamydomonas) on the three ultraplankton (<5 μm in diameter) cells (a coccoid bacterium and the algae Synechococcus and Nannochloris) varied greatly among zooplankton species but were not correlated with zooplankton body length. Variation in ERs on a much larger (17 × 14 μm) algal cell (Cryptomonas) was only partly explained by zooplankton body length. The eight zooplankton species were classified into three functional groups: (i) species having moderate to high ERs on all ultraplankton (0.4 < ER < 1.6) and ERs on Cryptomonas proportional to their body lengths (Conochilus, Diaphanosoma, and probably Keratella cochlearis and Ceriodaphnia); (ii) species having extremely low ERs on bacteria (mean ER < 0.05), higher but still low ERs on ultraphytoplankton (ER generally < 0.4), and ERs on Cryptomonas proportional to their body lengths (Bosmina, Diaptomus copepodites and adults); (iii) species having extremely low ERs on all ultraplankton (mean ER < 0.05) and ERs on Cryptomonas much higher than expected given their body lengths (Keratella crassa, Polyarthra, and Diaptomus nauplii). These functional groups follow neither taxonomic nor body-length groupings. We conclude that zooplankton body length may influence the maximal particle size a species can ingest but has little influence on the ingestion of smaller particles. Two frequently used models relating zooplankton body size and food size are unrealistic.     

Evolution of white matter tract microstructure across the life span

The human brain undergoes dramatic structural change over the life span. In a large imaging cohort of 801 individuals aged 7–84 years, we applied quantitative relaxometry and diffusion microstructure imaging in combination with diffusion tractography to investigate tissue property dynamics across the human life span. Significant nonlinear aging effects were consistently observed across tracts and tissue measures. The age at which white matter (WM) fascicles attain peak maturation varies substantially across tissue measurements and tracts. These observations of heterochronicity and spatial heterogeneity of tract maturation highlight the importance of using multiple tissue measurements to investigate each region of the WM. Our data further provide additional quantitative evidence in support of the last‐in‐first‐out retrogenesis hypothesis of aging, demonstrating a strong correlational relationship between peak maturational timing and the extent of quadratic measurement differences across the life span for the most myelin sensitive measures. These findings present an important baseline from which to assess divergence from normative aging trends in developmental and degenerative disorders, and to further investigate the mechanisms connecting WM microstructure to cognition.     

Gender differences in clinicopathological features and survival in surgically treated patients with renal cell carcinoma: an analysis of the multicenter CORONA database

Purpose

To investigate gender differences in clinicopathological features and to analyze the prognostic impact of gender in renal cell carcinoma (RCC) patients undergoing surgery.

Methods

A total of 6,234 patients (eleven centers; Europe and USA) treated by radical or partial nephrectomy were included in this retrospective study (median follow-up 59 months; IQR 30–106). Gender differences in clinicopathological parameters were assessed. Multivariable Cox regression models were applied to determine the influence of parameters on disease-specific survival (DSS) and overall survival (OS).

Results

A total of 3,751 patients of the study group were male patients (60.2 %), who were significantly younger at diagnosis and received more frequently NSS than women. Significantly, more often high-grade tumors and simultaneous metastasis were present in men. Whereas tumor size and pTN stages did not differ between genders, clear-cell and chromophobe RCC was diagnosed less frequently, but papillary RCC more often in men. Gender also independently influenced DSS (HR 0.75, p < 0.001) and OS (HR 0.80, p < 0.001) with a benefit for women. However, inclusion of gender in multivariable models did not significantly gain predictive accuracies (PA) for DSS (0.868–0.870, p = 0.628) and OS (0.775–0.777, p = 0.522). Furthermore, no significantly different DSS and OS rates were found in patients undergoing NSS.

Conclusions

This study demonstrates important gender differences in clinicopathological features and outcome of RCC patients with improved DSS and OS for women compared to men, even if solely patients with clear-cell RCC or M0-stage are taken into evaluation. However, inclusion of gender in multivariable models does not significantly gain PA of multivariable models.