The Influence of Betulin and Its Derivatives EB5 and ECH147 on the Antioxidant Status of Human Renal Proximal Tubule Epithelial Cells

Betulin and its derivatives, 28-propyne derivative EB5 and 29-diethyl phosphonate analog ECH147, are promising compounds in anti-tumor activity studies. However, their effect on kidney cells has not yet been studied. The study aimed to determine whether betulin and its derivatives—EB5 and ECH147—influence the viability and oxidative status of human renal proximal tubule epithelial cells (RPTECs). The total antioxidant capacity of cells (TEAC), lipid peroxidation product malondialdehyde (MDA) level, and activity of antioxidant enzymes (SOD, CAT, and GPX) were evaluated. Additionally, the mRNA level of genes encoding antioxidant enzymes was assessed. Cisplatin and 5-fluorouracil were used as reference substances. Betulin and its derivatives affected the viability and antioxidant systems of RPTECs. Betulin strongly reduced TEAC in a concentration-dependent manner. All tested compounds caused an increase in MDA levels. The activity of SOD, CAT, and GPX, and the mRNA profiles of genes encoding antioxidant enzymes depended on the tested compound and its concentration. Betulin showed an cisplatin-like effect, indicating its nephrotoxic potential. Betulin derivatives EB5 and ECH147 showed different impacts on the antioxidant system, which gives hope that these compounds will not cause severe consequences for the kidneys in vivo.     

Estrogen Receptors Mediated Negative Effects of Estrogens and Xenoestrogens in Teleost Fishes—Review

Estrogen receptors (ERs) play a key role in many biochemical and physiological processes, that are involved in maintaining organism homeostasis. At the most basic level, they can be divided into nuclear estrogen receptors and membrane estrogen receptors that imply their effect in two ways: slower genomic, and faster non-genomic. In these ways, estrogens and xenoestrogens can negatively affect animal health and welfare. Most of the available literature focuses on human and mammalian physiology, and clearly, we can observe a need for further research focusing on complex mutual interactions between different estrogens and xenoestrogens in aquatic animals, primarily fishes. Understanding the mechanisms of action of estrogenic compounds on the ERs in fishes and their negative consequences, may improve efforts in environmental protection of these animals and their environment and benefit society in return. In this review, we have summarized the ER-mediated effects of xenoestrogens and estrogens on teleost fishes metabolism, their carcinogenic potential, immune, circulatory, and reproductive systems.     

Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) represents a major burden to global health, and refined vaccines are needed. Replication-deficient lymphocytic choriomeningitis virus (rLCMV)-based vaccine vectors against cytomegalovirus have proven safe for human use and elicited robust T cell responses in a large proportion of vaccine recipients. Here, we developed an rLCMV vaccine expressing the Mtb antigens TB10.4 and Ag85B. In mice, rLCMV elicited high frequencies of polyfunctional Mtb-specific CD8 and CD4 T cell responses. CD8 but not CD4 T cells were efficiently boosted upon vector re-vaccination. High-frequency responses were also observed in neonatally vaccinated mice, and co-administration of rLCMV with Expanded Program of Immunization (EPI) vaccines did not result in substantial reciprocal interference. Importantly, rLCMV immunization significantly reduced the lung Mtb burden upon aerosol challenge, resulting in improved lung ventilation. Protection was associated with increased CD8 T cell recruitment but reduced CD4 T cell infiltration upon Mtb challenge. When combining rLCMV with BCG vaccination in a heterologous prime-boost regimen, responses to the rLCMV-encoded Mtb antigens were further augmented, but protection was not significantly different from rLCMV or BCG vaccination alone. This work suggests that rLCMV may show utility for neonatal and/or adult vaccination efforts against pulmonary tuberculosis.     

The Combination of Intestinal Alkaline Phosphatase Treatment with Moderate Physical Activity Alleviates the Severity of Experimental Colitis in Obese Mice via Modulation of Gut Microbiota,Attenuation of Proinflammatory Cytokines,Oxidative Stress Biomarkers and DNA Oxidative Damage in Colonic Mucosa

Inflammatory bowel diseases (IBD) are commonly considered as Crohn’s disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of Alistipes, lower proportion of Turicibacter, Proteobacteria and Faecalibacterium, an increase in Firmicutes and Clostridium, a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength.     

Label-Free Quantitative Proteomics Reveals Differences in Molecular Mechanism of Atherosclerosis Related and Non-Related to Chronic Kidney Disease

The major cause of mortality in patients with chronic kidney disease (CKD) is atherosclerosis related to traditional and non-traditional risk factors. However, the understanding of the molecular specificity that distinguishes the risk factors for classical cardiovascular disease (CVD) and CKD-related atherosclerosis (CKD-A) is far from complete. In this study we investigated the disease-related differences in the proteomes of patients with atherosclerosis related and non-related to CKD. Plasma collected from patients in various stages of CKD, CVD patients without symptoms of kidney dysfunction, and healthy volunteers (HVs), were analyzed by a coupled label-free and mass spectrometry approach. Dysregulated proteins were confirmed by an enzyme-linked immunosorbent assay (ELISA). All proteomic data were correlated with kidney disease development and were subjected to bioinformatics analysis. One hundred sixty-two differentially expressed proteins were identified. By directly comparing the plasma proteomes from HVs, CKD, and CVD patients in one study, we demonstrated that proteins involved in inflammation, blood coagulation, oxidative stress, vascular damage, and calcification process exhibited greater alterations in patients with atherosclerosis related with CKD. These data indicate that the above nontraditional risk factors are strongly specific for CKD-A and appear to be less essential for the development of “classical” CVD.     

Sprouted wheat grain with ferritin overexpression as a potential source of iron for cereal product fortification

Grains of winter wheat (Korweta variety) were partially germinated in an abiotic stress condition (0–15 mM FeSO₄ solutions) in order to accumulate iron by ferritin overexpression. The physical, chemical, biochemical properties and technological parameters of the obtained material as well as their resistance to an insect storage pest—granary weevil—were analyzed. Sprouted wheat grains with overexpression of ferritin contain 52 times more iron, more than 50 % in form of ferritin. The contents of reducing sugars, crude protein, fiber and ash as well as amylolytic activity increased significantly in sprouted wheat grain, while starch, fat, wet gluten, falling number and inhibition activity against granary weevil α-amylase decreased. Germinated wheat grain enriched with iron strongly affected granary weevil developmental parameters. Despite the fact that technological parameters of the product were deteriorated, it is worth to consider this material application as an iron supplement for cereal products, when the application of soybean is impossible.     

Freshness and quality attributes of cold stored Atlantic bonito (Sarda sarda) gravad

Quality and safety parameters of Atlantic bonito gravad during 42 days of storage at 7 ± 1 °C were analysed using monitoring sensory quality, microbial contamination, nucleotide degradation products, biogenic amines (BA), trimethylamine (TMA) and thiobarbituric acid reactive substances (TBARS). The shelf‐life of vacuum packed Atlantic bonito gravad was found to be 28 days. Total viable count (TVC) did not exceed 6 log CFU g^?1. Malonodialdehyde (MDA) content did not surpass 10 mg kg^?1. Nine biogenic amines were detected. Histamine level at the end of the storage was 355.3 mg kg^?1. TMA increased from 53.9 to 619.1 mg kg^?1. Among indicators based on the products of nucleotide degradation, the H value is best correlated with the sensory assessment. It can be concluded that the storage temperature of bonito gravad must be below 7 °C to prevent the threat to safety and quality posed by biogenic amines, especially histamine.     

Behavior of Cetyltrimethylammonium Bromide, tert-Octylphenol (9.5 EO) Ethoxylate and Ethanol Mixtures at the Water–Air Interface

The surface tension measurements of aqueous solutions of p‐(1,1,3,3‐tetramethylbutyl)phenoxypoly(9.5)ethylene glycol or tert‐octylphenol ethoxylate (TOP10) and cetyltrimethylammonium bromide (CTAB) mixtures with ethanol were carried out in the range of the total concentration of CTAB and TOP10 mixtures from 1 × 10^?7 to 1 × 10^?2 M and ethanol from 0 to 17.13 M. In the CTAB and TOP10 mixtures, the mole fractions of TOP10 were equal to 0.2; 0.4; 0.6; and 0.8, respectively. The results obtained were compared to those calculated from the Fainerman and Miller equation developed for ideal mixtures of two homologous surfactants, as well as from the Connors equation derived for the concentrated organic solutions. The calculations of the surface tension from the Fainerman and Miller equation were carried out treating the solvent and solute in a few different ways. The differences between the measured and calculated values of the surface tension were discussed in the light of molecular interaction parameter and the composition of the surface layer. The composition of the mixed surface layer at the solution‐air interface was evaluated according to Rosen using the nonideal solution theory with the assumption that water with ethanol is a mixed solvent. Knowing the values of mole fractions of CTAB and TOP10 in the surface layer, the molecular interaction parameter was determined.