No abstract

There are many discrepancies among the results of studies on the genotoxicity of lead. The aim of the study was to explore lead-induced DNA damage, including oxidative damage, in relation to oxidative stress intensity parameters and the antioxidant defense system in human leukocytes. The study population consisted of 100 male workers exposed to lead. According to the blood lead (PbB) levels, they were divided into the following three subgroups: a group with PbB of 20–35 μg/dL (low exposure to lead (LE) group), a group with a PbB of 35–50 µg/dL (medium exposure to lead (ME) group), and a group with a PbB of >50 μg/dL (high exposure to lead (HE) group). The control group consisted of 42 healthy males environmentally exposed to lead (PbB < 10 μg/dL). A comet assay was used to measure the DNA damage in leukocytes. We measured the activity of superoxide dismutase (SOD), catalase, glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-S-transferase (GST) as well as the concentration of malondialdehyde (MDA), and the value of the total antioxidant capacity. The level of PbB was significantly higher in the examined subgroups than in the control group. The percentage of DNA in the tail was significantly higher in the LE, ME, and HE subgroups than in the control group by 10% ( p = 0.001), 15% ( p < 0.001), and 20% ( p < 0.001), respectively. The activity of GR was significantly lower in the LE and ME subgroups than in the control group by 25% ( p = 0.007) and 17% ( p = 0.028), respectively. The activity of G6PD was significantly lower in the ME subgroup by 25% ( p = 0.022), whereas the activity of GST was significantly higher in the HE subgroup by 101% ( p = 0.001) than in the control group. Similarly, the activity of SOD was significantly higher in the LE and ME subgroups by 48% ( p = 0.026) and 34% ( p = 0.002), respectively. The concentration of MDA was significantly higher in the LE, ME, and HE subgroups than in the control group by 43% ( p = 0.016), 57% ( p < 0.001), and 108% ( p < 0.001), respectively. Occupational lead exposure induces DNA damage, including oxidative damage, in human leukocytes. The increase in DNA damage was accompanied by an elevated intensity of oxidative stress.

The worldwide distribution of microinvertebrates on glaciers, the coldest biome, is poorly known. Owing to their tolerance to hostile conditions, small size and dispersal abilities, nematodes, tardigrades and rotifers are considered cosmopolitan and together inhabit various ecosystems. In this study, we investigated their global distribution in cryoconite holes – a type of freshwater reservoir forming directly in the glacial ice that creates biodiversity hotspots on glaciers. We analysed cryoconite samples (using classical microscopic observations and environmental DNA metabarcoding) from 42 glaciers located around the world (the Arctic, Subarctic, Scandinavia, the Alps, the Caucasus, Siberia, Central Asia, Africa, South America and Antarctica), as well as using literature data. Samples from Antarctic, Karakoram and the Alps were analysed using next‐generation sequencing (NGS) and classical observations under microscopes, while all other samples were analysed by microscope alone. Three general outcomes were found: (1) tardigrades and rotifers represented the most common invertebrates in cryoconite holes; (2) tardigrades and rotifers often coexisted together, with one or the other dominating, but the dominant taxon varied by region or by glacier; (3) nematodes – the most abundant, hyperdiverse and widespread metazoans on Earth, including in environments surrounding and seeding glacial surfaces – were consistently absent from cryoconite holes. Despite the general similarity of environmental conditions in cryoconite holes, the distribution of tardigrades and rotifers differed among glaciers, but not in any predictable way, suggesting that their distribution mostly depended on the random dispersal, extreme changes of supraglacial zone or competition. Although nematodes have been found in supraglacial habitats, cryoconite hole environments seem not to provide the necessary conditions for their growth and reproduction. Lack of physiological adaptations to permanently low temperatures (~0°C) and competition for different food resources in the cryoconite hole environment may explain the absence of nematodes in cryoconite holes.

In the presented study, transportan 10 (TP10), an amphipathic cell penetrating peptide (CPP) with high translocation activity, was conjugated with vancomycin (Van), which is known for poor access to the intracellular bacteria and the brain. The antibacterial activity of the conjugates was tested on selected clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus sp . It turned out that all of them had superior antimicrobial activity in comparison to that of free Van, which became visible particularly against clinical MRSA strains. Furthermore, one of the conjugates was tested against MRSA - infected human cells. With respect to them, this compound showed high bactericidal activity. Next, the same conjugate was screened for its capacity to cross the blood brain barrier (BBB). Therefore, qualitative and quantitative analyses of the conjugate’s presence in the mouse brain slices were carried out after its iv administration. They indicated the conjugate’s presence in the brain in amount >200 times bigger than that of Van. The conjugates were safe with respect to erythrocyte toxicity (erythrocyte lysis assay). Van in the form of a conjugate with TP10 acquires superior pharmacodynamic and pharmacokinetic.

I nsulin resistance has been described as associated with low levels of mannanbinding lectin (MBL), a protein of the innate immune system (1). The aim of the present study was to study serum MBL concentration in polycystic ovary syndrome (PCOS) in relation to insulin resistance, adiponectin, and high-sensitivity C-reactive protein (hsCRP). Insulin sensitivity, serum MBL concentration, adiponectin, hsCRP, and sex hormones were measured in 102 PCOS (34 of whom were lean and 68 overweight or obese) and 50 healthy (28 lean and 22 overweight or obese) women. The diagnosis of PCOS was done according to Rotterdam Consensus Criteria. In the factorial ANOVA, we observed that both PCOS (P Ͻ 0.001) and obesity (P ϭ 0.034) independently contributed to lower serum MBL (in those with obese PCOS, 1,786.92 Ϯ 1,747.02; lean PCOS, 2,304.68 Ϯ 2,137.35; obese control, 2,969.88 Ϯ 2,615.97; and lean control, 4,007.87 Ϯ 2,132.62 g/l; P ϭ 0.54 for the interaction) and lower insulin sensitivity (obese PCOS, 7.20 Ϯ 3.29; lean PCOS, 9.52 Ϯ 3.75; obese control, 9.05 Ϯ 3.16; and lean control, 11.38 Ϯ 3.07 mg ⅐ kg fat-free mass Ϫ1 ⅐ min Ϫ1 [PCOS, P ϭ 0.002; obesity, P Ͻ 0.001; P ϭ 0.99 for the interaction]). Serum adiponectin was lower (P Ͻ 0.001) and hsCRP was higher (P ϭ 0.0011) in the obese women, whereas PCOS had no effect.Serum MBL level was positively related to insulin sensitivity (r ϭ 0.29, P ϭ 0.00025). This relationship persisted after controlling for age, BMI, waist circumference, serum cholesterol, fasting triglycerides, HDL cholesterol, and adiponectin (all adjusted ␤-values between 0.19 and 0.29, all P Ͻ 0.01). Serum MBL was also negatively associated with hsCRP (r ϭ Ϫ0.24, P ϭ 0.006). We did not find any association between MBL and markers of hyperandrogenism, suggesting that low MBL is connected with insulin resistance and proinflammatory activity rather than with PCOS per se. We demonstrated that in PCOS women, decreased MBL levels might contribute to insulin resistance and thus to an increased risk of type 2 diabetes and cardiovascular disease.

The negative health effects caused by lead (Pb) exposure are widely recognized; however, the molecular mechanisms remain unknown. The aim of this study was to assess the effect of occupational Pb exposure on telomere length and to investigate the potential mechanisms leading to telomere shortening. A cohort of 334 male Pb smelters (exposed group) and 60 age-adjusted males unexposed to Pb (control group) were examined. Assessments of relative telomere length (rTL) and telomerase reverse transcriptase (TERT) gene expression were performed using quantitative real-time polymerase chain reactions. Assessments of whole blood Pb (B-Pb) and whole blood cadmium (B-Cd) concentrations and serum selenium concentration (S-Se) were performed using graphite furnace atomic absorption spectrometry. We analyzed total oxidation status (TOS), lipid hydroperoxides (LHPs), malonylodialdehyde levels in serum (MDA) and in erythrocyte hemolysates (MDA-hgb), and 8-hydroxy-deoxy-guanosine (8-OHdG). The Pb-exposed group had higher B-Pb values and shorter rTL than the control group. The arithmetic mean values calculated for B-Pb were 33 µg/dL versus 2.2 µg/dL (p < 0.0001), and the rTL values were 0.928 and 1.126 relative units (p = 0.001), respectively, for the Pb-exposed and control groups. The rTL was found to gradually shorten in response to the increasing levels of Pb exposure. The Pb-exposed group also demonstrated a higher level of oxidative stress than the control group, which was indicated by increased TOS and MDA-hgb values. rTL was negatively associated with parameters that indicated increased oxidative stress, including TOS (Spearman's rank coefficient (r) = -0.16; p < 0.01) and MDA-hgb (r = -0.17; p < 0.001). No correlations were found between rTL and B-Cd and S-Se or smoking and MDA and LHP levels. Univariate analysis indicated that B-Pb was associated with decreased rTL (β =-0.0041; p = 0.0063) and that the association between B-Pb and rTL remained significant, even when adjusting for age (β = -0.0041; p = 0.0065) and in multivariable-adjusted model (β = -0.0042; p = 0.0063). In conclusion, occupational Pb exposure resulted in decreased rTL and may represent a mechanism that contributes to Pb-related diseases.

No abstract

Background. Exposure to lead (Pb) in environmental and occupational settings continues to be a serious public health problem and may pose an elevated risk of genetic damage.