Molecular mechanisms of zinc oxide nanoparticles neurotoxicity.

Zinc oxide nanoparticles (ZnONPs) are widely used in industry and biomedicine. A growing body of evidence demonstrates that ZnONPs exposure may possess toxic effects to a variety of tissues, including brain. Therefore, the objective of the present review was to summarize existing evidence on neurotoxic effects of ZnONPs and discuss the underlying molecular mechanisms. The existing laboratory data demonstrate that both in laboratory rodents and other animals ZnONPs exposure results in a significant accumulation of Zn in brain and nervous tissues, especially following long-term exposure. As a result, overexposure to ZnONPs causes oxidative stress and cell death, both in neurons and glial cells, by induction of apoptosis, necrosis and ferroptosis. In addition, ZnONPs may induce neuroinflammation through the activation of nuclear factor kappa B (NF-κB), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and lipoxygenase (LOX) signaling pathways. ZnONPs exposure is associated with altered cholinergic, dopaminergic, serotoninergic, as well as glutamatergic and γ-aminobutyric acid (GABA)-ergic neurotransmission, thus contributing to impaired neuronal signal transduction. Cytoskeletal alterations, as well as impaired autophagy and mitophagy also contribute to ZnONPs-induced brain damage. It has been posited that some of the adverse effects of ZnONPs in brain are mediated by altered microRNA expression and dysregulation of gut-brain axis. Furthermore, in vivo studies have demonstrated that ZnONPs exposure induced anxiety, motor and cognitive deficits, as well as adverse neurodevelopmental outcome. At the same time, the relevance of ZnONPs-induced neurotoxicity and its contribution to pathogenesis of neurological diseases in humans are still unclear. Further studies aimed at estimation of hazards of ZnONPs to human brain health and the underlying molecular mechanisms are warranted.

Serum Mineral Levels in Dairy Cows Transiting from Feedlot to Pasture.

The objective of the present study was to evaluate trace element and minerals levels in the serum of cows transiting from diets consumed in feedlot or under grazing. A total of 30 healthy 5-6 years old cows of the Red Steppe breed were involved in the study. Blood samples were collected at the end of the feedlot period (end of April) and during the pasture period (end of June). Serum essential trace element and mineral levels were evaluated using inductively coupled plasma mass spectrometry. The obtained data demonstrate that serum K levels in cows during the feedlot period exceeded those in the pasture period by 50%, whereas serum P values in the pasture period were significantly higher than in the feedlot period by 20%. Serum Li levels in cows during the feedlot feeding period were nearly 3-fold higher than the respective values in a pasture period. In addition, serum B, Sr, and Zn concentrations in cows during a pasture period exceeded those observed upon feedlot feeding by 38%, 40%, and 13%, respectively. In contrast, serum I and V levels in a feedlot period were 32% and 77% higher when compared to the respective values in a pasture period. Multiple regression analysis demonstrated that Cr, Cu, I, Na, and V are positively associated with feedlot feeding. At the same time, serum Zn and to a lesser extent Sr values were directly associated with the pasture period. Therefore, the results of the present study demonstrated that feedlot and pasture rations have a significant impact on trace element and mineral metabolism in dairy cows.

Serum and Hair Trace Element and Mineral Levels in Dairy Cows in Relation to Daily Milk Yield.

The objective of the present study was to assess hair and serum trace element and mineral levels in dairy cows in relation to daily milk yield. A total of 70 healthy 5-6-year-old Simmental cows were divided into two groups (n = 35) with high and low daily milk yield using median as a cut-off value. Hair and serum trace element and mineral content was evaluated using inductively coupled plasma mass-spectrometry. A nearly twofold difference in daily milk yield (43.8 ± 9.7 vs 21.3 ± 7.1 L/day, p < 0.001) was significantly associated with 11% lower hair Cu (p = 0.043) and 35% higher Se levels (p = 0.058) content when compared animals with lower daily milk yield. Serum trace element levels were found to be more tightly associated with milk productivity in dairy cows. Particularly, serum levels of Se and Zn were found to be 73 and 35% higher in cows with higher milk productivity in comparison to animals with lower milk production, respectively. Serum Co levels also tended to increase with higher milk productivity. Serum minerals including Ca, Mg, and P were also found to be higher in highly productive cows by 6%, 14%, and 71%, respectively. The overall regression model based on serum trace element and mineral levels accounted for 38% of daily milk production variability. Generally, improvement of essential trace element and mineral supply, as well as prevention of copper overload in dairy cows, may be considered the potential tool for modulation of milk productivity.

Speciation of Serum Copper and Zinc-Binding High- and Low-Molecular Mass Ligands in Dairy Cows Using HPLC-ICP-MS Technique.

The objective of the present study was assessment of the major copper and zinc species in dairy cow blood serum using a hybrid high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) technique. A total of seventeen 5-6-year-old female Simmental cows, cultivated in the Southern Ural region, were examined. Speciation of serum Cu and Zn was performed using chromatographic PerkinElmer Series 200 system equipped with Agilent Bio SEC-5 Column and docked with NexION 300D mass spectrometer. Analysis of serum 63Cu species revealed four major fractions containing 2.5% (A), 15.6% (B), 75.6% (C), and 11.9% (D) of total copper levels. The revealed fractions could be assigned to tetrameric and dimeric macroglobulin, ceruloplasmin, albumin, and low molecular mass (LMM) copper compounds, respectively. Minor fraction (E) containing <1% of total serum Cu levels may be represented by low-molecular mass Cu species. Speciation analysis also revealed four Zn fractions containing 6.3% (A), 16.9% (B), 71% (C), and 3% (D) of total Zn levels that may be attributed to zinc-bound tetrameric and dimeric macroglobulin, albumin, and Zn-amino acid compounds. Correlation analysis demonstrated that relative levels (%) of Zn-B (dimeric α2-macroglobulin), Zn-C (albumin), and Zn-D (LMM) fractions correlate inversely with Cu-A (monomeric α2-macroglobulin) (r = -0.600), Cu-D (albumin) (r = -0.696), and Cu-C (ceruloplasmin) (r = -0.652), respectively. The obtained data demonstrate the particular features of Zn and Cu transport in dairy cows that may be used for assessment of dietary status of trace elements.

Data on rumen and faeces microbiota profiles of Yakutian and Kalmyk cattle revealed by high-throughput sequencing of 16S rRNA gene amplicons.

It is known that the rumen microbiome directly or indirectly contributes to animal production, and may be a prospective target for mitigation of greenhouse gas emissions [1]. At the same time, feed types and components of diet can influence the composition of the rumen microbiome [2,3]. Fluctuations in the composition of the digestive tract microbiota can alter the development, health, and productivity of cattle [4]. Many studies of cattle microbiomes have focussed on the rumen microbiota, whereas the faecal microbiota has received less attention [5], [6], [7]. Therefore, the features of the faecal and the ruminal microbiomes in different cattle breeds are yet to be studied. Here, we provided 16S rRNA gene amplicon data of the ruminal and the faecal microbiomes from Yakutian and Kalmyk cattle living in the Republic of Sakha, Yakutia, Russia. Total DNA was extracted from 13 faecal and 13 ruminal samples, and DNA libraries were prepared and sequenced on an Illumina MiSeq platform. Paired-end raw reads were processed, and final operational taxonomic units (OTUs) were assigned to the respective prokaryotic taxa using the RDP (Ribosomal Database Project) database. Analysis of the microbiome composition at the phylum level revealed very similar faecal microbiota between the introduced Kalmyk breed and the indigenous Yakutian breed, whereas the ruminal microbiomes of these breeds differed substantially in terms of relative abundance of some prokaryotic phyla. We believe that the data obtained may provide new insights into the dynamics of the ruminal and the faecal microbiota of cattle as well as disclose breed-specific features of ruminal microbiomes. Besides, these data will contribute to our understanding of the ruminal microbiome structure and function, and might be useful for the management of cattle feeding and ruminal methane production.

Assessment of Gender Effects and Reference Values of Mane Hair Trace Element Content in English Thoroughbred Horses (North Caucasus, Russia) Using ICP-DRC-MS.

The objective of the present study was assessment of gender differences in hair trace element content in English Thoroughbred horses (North Caucasus, Russia) using ICP-DRC-MS and calculation of the reference values. Trace element content in mane hair of 190 stallions and 94 mares (3-7 years old) bred in North Caucasus (Russia) was assessed using inductively coupled plasma mass spectrometry. Mane hair Co, Cr, Mn, Li, Si, and Sr levels in mares exceeded those in stallions by 77%, 63%, 64%, 42%, 39%, and 64%, respectively. Hair Fe and Si content was nearly twofold higher in female horses as compared to the males. Only hair Zn content was 5% higher in stallions as compared to mares. In addition, mares were characterized by 63%, 65%, 29%, and 40% higher levels of As, Pb, Sn, and Ni levels in hair as compared to the respective values in stallions. In turn, hair Al and Hg were more than twofold higher in mares than in stallions. The reference intervals of mane hair content (µg/g) for Co (0.006-0.143), Cr (0.028-0.551), Cu (4.17-6.84), Fe (10.11-442.2), I (0.026-3.69), Mn (0.551-12.55), Se (0.108-0.714), Zn (97.43-167), Li (0.011-0.709), Ni (0.060-0.589), Si (0.665-29.12), V (0.006-0.584), Al (1.98-168.5), As (0.006-0.127), Cd (0.002-0.033), B (0.494-16.13), Pb (0.018-0.436), Sn (0.002-0.144), Sr (1.0-9.46), and Hg (0.0018-0.017) in the total cohort of horses were estimated using the American Society for Veterinary Clinical Pathology Quality Assurance and Laboratory Standard Guidelines. The reference intervals were also estimated for stallions and mares bred in North Caucasus (Russia) and may be used for interpretation of the results of hair trace element analysis in horses.

The Reference Intervals of Hair Trace Element Content in Hereford Cows and Heifers (Bos taurus).

The objective of the present study was to assess hair trace element content in Hereford heifers and cows (Bos taurus) living in South Ural region and calculate the site-specific reference intervals. Hair trace element content in 150 cows and heifers farmed in the Southern Urals of Russia was assessed using inductively coupled plasma mass-spectrometry. Dietary trace element content corresponded to the adequate values as estimated by recommendations of USSR State Agriculture Committee and U.S. National Research Council. Comparative analysis demonstrated that heifers are characterized by significantly higher hair Se (3-fold), Hg (4-fold), and Sn (46%) content, whereas cows had significantly higher levels of hair Co (56%), I (33%), Si (2-fold), V (27%), B (55%), Cd (19%), Pb (47%), and Sr (23%). At the same time, no significant group difference in hair Cr, Cu, Fe, Li, Mn, Zn, As, and Ni was detected between Hereford cows and heifers. The reference intervals and 90% confidence intervals for the lower and upper limits were calculated in agreement with the American Society for Veterinary Clinical Pathology Quality Assurance and Laboratory Standard Guidelines.

Effective Treatment of Staphylococcal Scalded Skin Syndrome with Platelet Microbicidal Protein in CBRB-Rb(8.17)1Iem Mice Model.

Skin and soft-tissue infections are among the most common infections. Staphylococcus aureus may cause a number of toxin-mediated diseases, including staphylococcal scalded skin syndrome (SSSS). The therapeutic efficacy of some antimicrobial peptides was recently evaluated in a mouse model of SSSS. This study is the first in vivo demonstration of the use of PMP to improve outcome of SSSS. Twenty-four CBRB-Rb(8.17)1Iem female mice naturally infected by endogenous S. aureus with SSSS symptoms were used in this work and divided into two equal groups. From neck of each mouse was isolated and identified endogenous exfoliative producing strain of S. aureus. PMP was obtained from human platelets and tested against Bacillus subtilis ATCC 6633. PMP had bactericidal activity against B. subtilis ATTC 6633 and endogenous strain of S. aureus at 2.0 ± 0.5 and 14.5 ± 0.5 µg/ml, respectively. At 4 weeks, the mice of experimental group were treated subcutaneous near exfoliative zone with 0.2 ml of PMP in final concentration 10 µg/ml every day. Control mice was injected with 0.2 ml 0.9% NaCl. At 1 day of experiment maximal zone of alopecia was at PMP-treating group (380 ± 20 mm(2)) in comparison with control group (167 ± 10 mm(2), p < 0.01). At 50 day of observation (22nd day after the end of treatment), the square of alopecia in control group was 1220 ± 40 mm(2) in comparison with 870 ± 17 mm(2) in experimental group (p < 0.01). The antistaphylococcal in vivo activity of PMP demonstrated in present study makes these molecules potentially useful for treatment of SSSS.

Evaluation of antitumor activity of platelet microbicidal protein on the model of transplanted breast cancer in CBRB-Rb(8.17)1Iem mice.

Breast cancer is the most common women's cancer in the world. There is considerable current interest in developing anticancer agents with a new mode of action because of the development of resistance by cancer cells towards current anticancer drugs. Mamalian cells have been shown to contain small, cationic, microbicidal peptides. Antimicrobial peptides have drawn attention as a promising alternative to current antitumor agents. Such peptides have been isolated both from animal and human platelets and have been termed platelets microbicidal proteins (PMP). The aim of this work was to study antitumor activity of PMP in vivo on the model of mouse breast cancer in comparison with antitumor hexapeptide Arg-alpha-Asp-Lys-Val-Tyr-Arg (Immunofan). We demonstrated that the tumors treated with PMP were significant smaller than the control groups (P < 0.05). In experiments in vivo using CBRB-Rb(8.17)1Iem mice with transplanted tumors PMP inhibited tumor growth during the treatments and after its discontinuation. These findings indicate that PMP can exert antitumor effects. Therefore, PMP may be used for the development of therapy for the intervention of breast cancer.