Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model

4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol (C1) and 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl] benzene1,3-diol (NTBD) are representative derivatives of the thiadiazole group, with a high antimycotic potential and minimal toxicity against normal human fibroblast cells. The present study has proved its ability to synergize with the antifungal activity of AmB. The aim of this work was to evaluate the cytotoxic effects of C1 or NTBD, alone or in combination with AmB, on human renal proximal tubule epithelial cells (RPTECs) in vitro. Cell viability was assessed with the MTT assay. Flow cytometry and spectrofluorimetric techniques were used to assess the type of cell death and production of reactive oxygen species (ROS), respectively. The ELISA assay was performed to measure the caspase-2, -3, and -9 activity. ATR-FTIR spectroscopy was used to evaluate biomolecular changes in RPTECs induced by the tested formulas. The combinations of C1/NTBD and AmB did not exert a strong inhibitory effect on the viability/growth of kidney cells, as evidenced by the negligible changes in the apoptotic/necrotic rate and caspase activity, compared to the control cells. Both NTBD and C1 displayed stronger anti-oxidant activity when combined with AmB. The relatively low nephrotoxicity of the thiadiazole derivative combinations and the protective activity against AmB-induced oxidative stress may indicate their potential use in the therapy of fungal infections.     

Synthesis of polymer membranes of different porosity and their application for phenol removal from liquid phase

Preparation of polymeric membranes based on polyethersulfone (PES) modified by adding different amounts of a pore-forming agent (PVP) is presented, and potential application of the membranes obtained for removal of phenol from the liquid phase is examined. The addition of various amounts of PVP has been shown to bring about changes in the content of the surface oxygen groups, but has no significant effect on the chemical character of the groups and acidic groups dominate. Filtration by phenol solution leads to significant changes in the total content of surface oxides; however, the acidic groups remain dominant. Membranes characterized by higher porosity exhibited more stable and higher rejection ratio for phenol removal. Although all the membranes were characterized by similar rejection ratios for phenol removal, the cake resistance (Rc) and pore resistance (Rp) values were found to depend significantly on the structure and porosity of the membrane applied for filtration.     

Combined Model Calibration and Spatial Aggregation

A methodology is proposed for estimating a combined transportation model that accommodates spatial aggregation. It employs maximum likelihood estimation using a joint probability function that includes destination and mode choice simultaneously. The main contribution of the paper is the incorporation of a spatial aggregation strategy to validate the method when the survey data are insufficient. By aggregating small zones into larger districts, estimation of the trip distribution parameters can be achieved with limited data, while mode choice continues to be estimated using disaggregated data. Our results demonstrate that including trip distribution in the travel decision induces variations in the utility function parameter estimators obtained for the different travel modes when only mode choice is estimated. The methodology thus corrects omission bias.     

The effect of freezing on the hot air and microwave vacuum drying kinetics and texture of whole cranberries

Abstract

The aim of this study was to evaluate the effect of convective and cryogenic freezing, hot air convective drying (HACD) at 60, 70, 80, and 90?°C and microwave vacuum drying (MWVD) at 100, 150, 200, 300, 450, and 500?W on the drying kinetics and texture of whole cranberries. Effective moisture diffusivities and drying rates were higher, whereas drying times were shorter for the samples dried by MWVD compared with the samples processed by HACD. The drying kinetics of cranberries during MWVD was discussed based on the hypothesis postulating that changes in the drying rate of cranberries during MWVD can be explained by and correlated with changes in the pressure gradient on material surface. Cranberries processed by MWVD were characterized by significantly greater hardness, gumminess, and chewiness in comparison with HACD samples. MWVD was found to be an effective method for producing dried snacks characterized by hard and crispy texture and considerable resistance to stress associated with manufacturing, packaging, storage, and delivery. HACD produced brittle fruit that were difficult to store and transport and were not fully suitable for direct consumption. Convective freezing before MWVD improved the overall appearance of cranberries, whereas cryogenic freezing combined with high temperature HACD adversely influenced the drying rate and produced dried cranberries with suboptimal overall appearance.     

Cytokine Receptors—Regulators of Antimycobacterial Immune Response

Cytokine receptors are critical regulators of the antimycobacterial immune response, playing a key role in initiating and coordinating the recruitment and activation of immune cells during infection. They recognize and bind specific cytokines and are involved in inducing intracellular signal transduction pathways that regulate a diverse range of biological functions, including proliferation, differentiation, metabolism and cell growth. Due to mutations in cytokine receptor genes, defective signaling may contribute to increased susceptibility to mycobacteria, allowing the pathogens to avoid killing and immune surveillance. This paper provides an overview of cytokine receptors important for the innate and adaptive immune responses against mycobacteria and discusses the implications of receptor gene defects for the course of mycobacterial infection.     

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.     

The impact of the fusarium mycotoxin deoxynivalenol on the health and performance of broiler chickens

The aim of the present experiment was to investigate the effects of feeding grains naturally contaminated with Fusarium mycotoxins on morphometric indices of jejunum and to follow the passage of deoxynivalenol (DON) through subsequent segments of the digestive tract of broilers. A total of 45 1-d-old broiler chickens (Ross 308 males) were randomly allotted to three dietary treatments (15 birds/treatment): (1) control diet; (2) diet contaminated with 1 mg DON/kg feed; (3) diet contaminated with 5 mg DON/kg feed for five weeks. None of the zootechnical traits (body weight, body weight gain, feed intake, and feed conversion) responded to increased DON levels in the diet. However, DON at both dietary levels (1 mg and 5 mg DON/kg feed) significantly altered the small intestinal morphology. In the jejunum, the villi were significantly (P < 0.01) shorter in both DON treated groups compared with the controls. Furthermore, the dietary inclusion of DON decreased (P < 0.05) the villus surface area in both DON treated groups. The absolute or relative organ weights (liver, heart, proventriculus, gizzard, small intestine, spleen, pancreas, colon, cecum, bursa of Fabricius and thymus) were not altered (P > 0.05) in broilers fed the diet containing DON compared with controls. DON and de-epoxy-DON (DOM-1) were analyzed in serum, bile, liver, feces and digesta from consecutive segments of the digestive tract (gizzard, cecum, and rectum). Concentrations of DON and its metabolite DOM-1 in serum, bile, and liver were lower than the detection limits of the applied liquid chromatography coupled with mass spectrometry (LC-MS/MS) method. Only about 10 to 12% and 6% of the ingested DON was recovered in gizzard and feces, irrespective of the dietary DON-concentration. However, the DON recovery in the cecum as percentage of DON-intake varied between 18 to 22% and was not influenced by dietary DON-concentration. Interestingly, in the present trial, DOM-1 did not appear in the large intestine and in feces. The results indicate that deepoxydation in the present study hardly occurred in the distal segments of the digestive tract, assuming that the complete de-epoxydation occurs in the proximal small intestine where the majority of the parent toxin is absorbed. In conclusion, diets with DON contamination below levels that induce a negative impact on performance could alter small intestinal morphology in broilers. Additionally, the results confirm that the majority of the ingested DON quickly disappears through the gastrointestinal tract.     

Resorcylidene Aminoguanidine (RAG) Improves Cardiac Mitochondrial Bioenergetics Impaired by Hyperglycaemia in a Model of Experimental Diabetes

Diabetes is associated with a mitochondrial dysfunction. Hyperglycaemia is also clearly recognized as the primary culprit in the pathogenesis of cardiac complications. In response to glycation and oxidative stress, cardiac mitochondria undergo cumulative alterations, often leading to heart deterioration. There is a continuous search for innovative treatment strategies for protecting the heart mitochondria from the destructive impact of diabetes. Aminoguanidine derivatives have been successfully used in animal model studies on the treatment of experimental diabetes, as well as the diabetes-driven dysfunctions of peripheral tissues and cells. Considerable attention has been paid particularly to β-resorcylidene aminoguanidine (RAG), often shown as the efficient anti-glycation and anti-oxidant agent in both animal studies and in vitro experiments. The aim of the present study was to test the hypothesis that RAG improves oxidative phosphorylation and electron transport capacity in mitochondria impaired by hyperglycaemia. Diabetes mellitus was induced in Wistar rats by a single intraperitoneal injection of streptozotocin (70 mg/kg body weight). Heart mitochondria were isolated from healthy rats and rats with streptozotocin-diabetes. Mitochondrial respiratory capacity was measured by high resolution respirometry with the OROBOROS Oxygraph-2k according to experimental protocol including respiratory substrates and inhibitors. The results revealed that RAG protects the heart against diabetes-associated injury by improving the mitochondrial bioenergetics, thus suggesting a possible novel pharmacological strategy for cardioprotection.