Hexokinase 2 Inhibition and Biological Effects of BNBZ and Its Derivatives: The Influence of the Number and Arrangement of Hydroxyl Groups

Hexokinase 2 (HK2), an enzyme of the sugar kinase family, plays a dual role in glucose metabolism and mediating cancer cell apoptosis, making it an attractive target for cancer therapy. While positive HK2 expression usually promotes cancer cells survival, silencing or inhibiting this enzyme has been found to improve the effectiveness of anti-cancer drugs and even result in cancer cell death. Previously, benitrobenrazide (BNBZ) was characterized as a potent HK2 inhibitor with good anti-cancer activity in mice, but the effect of its trihydroxy moiety (pyrogallol-like) on inhibitory activity and some cellular functions has not been fully understood. Therefore, the main goal of this study was to obtain the parent BNBZ (2a) and its three dihydroxy derivatives 2b–2d and to conduct additional physicochemical and biological investigations. The research hypothesis assumed that the HK2 inhibitory activity of the tested compounds depends on the number and location of hydroxyl groups in their chemical structure. Among many studies, the binding affinity to HK2 was determined and two human liver cancer cell lines, HepG2 and HUH7, were used and exposed to chemicals at various times: 24 h, 48 h and 72 h. The study showed that the modifications to the structures of the new BNBZ derivatives led to significant changes in their activities. It was also found that these compounds tend to aggregate and exhibit toxic effects. They were found to contribute to: (a) DNA damage, (b) increased ROS production, and (c) disruption of cell cycle progression. It was observed that, HepG2, occurred much more sensitive to the tested chemicals than the HUH7 cells; However, regardless of the used cell line it seems that the increase in the expression of HK2 in cancer cells compared to normal cells which have HK2 at a very low level, is a serious obstacle in anti-cancer therapy and efforts to find the effective inhibitors of this enzyme should be intensified.     

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.     

Nanomedicine-Based Delivery Strategies for Breast Cancer Treatment and Management

Breast cancer is one of the most common types of cancer among women globally. It is caused by mutations in the estrogen/progesterone receptors and conventional treatment methods are commonly utilized. About 70–80 percent of individuals with the early-stage non-metastatic disease may be cured. Conventional treatment is far less than the optimal ratio, as demonstrated through the high mortality rate of women with this cancer. However, conventional treatment methods like surgery, radiotherapy, and chemotherapy are not as effective as expected and lead to concerns about low bioavailability, low cellular uptake, emerging resistance, and adverse toxicities. A nanomedicine-based approach is a promising alternative for breast cancer treatment. The present era is witnessing rapid advancements in nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. This paper focuses on nanomedicine-based therapeutic interventions that are becoming more widely accepted for improving treatment effectiveness and reducing undesired side effects in breast cancer patients. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.     

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.     

Behaviour of Dietary Fibre Supplements During Bread Dough Development Evaluated Using Novel Farinograph Curve Analysis

A regression model composed of two sigmoid functions with variable asymptotes was developed and used to analyse the dietary fibre supplement behaviour during bread dough mixing. Using eight commercial dietary fibres of different botanical origin and model wheat starch-gluten flour, farinograph curves for fibre-flour blends and for the flour only were performed. After smoothing of the curves with the regression model, difference farinograms as the fibre supplementation effects were determined. The results showed that the difference farinograms had two peaks, whose shape was strongly differentiated by the studied supplements. The presence of both peaks allowed distinguishing two kinds of the rheological activity of each fibre supplement: weakening and strengthening of the consistency of bread dough during its development. The carrot, oat, cranberry, and cacao fibres exhibited dominance of strengthening over weakening action. While chokeberry, carob, apple, and flax fibres were characterised by dominance of weakening over strengthening action. The analysis of both position and height of the peaks in the difference farinogram can be also helpful for determination of hydration kinetics of the fibres used for bread supplementation.     

N‐Oligo(3‐hydroxybutyrate)‐functionalized polypyrroles: towards bio‐erodible conducting copolymers

New copolymer materials have been prepared by chemical grafting of oligomeric 3‐hydroxybutyric acid (OHB) onto polypyrrole (PPy) derivatives. The influence of grafting density and molecular weight of OHB brushes on the physicochemical properties of prepared copolymers was investigated. PPy substrates were prepared by FeCl₃‐driven oxidative homopolymerization of N‐(2‐carboxyethyl)pyrrole or its copolymerization with pyrrole. The grafting method employed involved controlled anionic polymerization of β‐butyrolactone on pyrrole‐tethered potassium carboxylate active sites. Obtained PPy‐g‐OHB copolymers of varying grafting density and pendant polyester chain length were characterized and the observed structure–property relationships discussed. The impact of real time exposure to phosphate‐buffered saline environment was investigated and the residue products were characterized. Cross‐correlation of spectroscopic, thermal, electrical and elemental analysis data afforded comprehensive evaluation of the structure of prepared materials and their behaviour in hydrolytic medium. Erosion and degradation pathways have been identified, indicating ways to consciously tailor the physicochemical properties of these new biomimetic materials. © 2016 Society of Chemical Industry     

Application of biosensors in early detection of contamination with lactic acid bacteria during apple juice and concentrate production

The aim of Collective Research Project QUALI-JUICE (COLL-CT-2005, Co Nr 012461) was to introduce the biosensors in control of microbiologically pure apple juice production. Three commercial lactate biosensors were used and compared with enzyme kits assays. Parallel the microbiological analysis of the production process at one juice producing enterprise was done. The results of lactic acid assay with biosensors were in good correlation with those obtained by enzyme kits. The main benefit of biosensor use was shortening of measurement time as compared with assay by enzyme kit and possibility to measure at line. The concentration of l-lactic acid in apple pulp could be correlated with the number of lactic acid bacteria. Pasteurization process was eliminating lactic acid bacteria and the concentration of lactic acid was at this stage not exceeding 0.1 g L⁻¹. The final product (apple concentrate) contained in some cases very high amounts of lactic acid indicating secondary microbiological contamination after pasteurization step. Parallel microbiological analysis of production process and lactate assay indicated that the critical point during production was prolonged vacuum filtration after pasteurization.     

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.     

Stripping of copper coatings from steel in Cr(VI)-free commercial bath

In this work the electrochemical characteristics of copper and steel in chromate, cyanide, and phosphate baths as well as in a commercial bath (ENSTRIP S-180), in the absence of chromium and cyanides were determined. Average rates of copper coatings stripping from steel in the above mentioned baths and the baths influence on the morphology of steel surfaces were described. It was found that the commercial bath ENSTRIP S-180 could be successfully used for stripping of copper coatings from steel elements.