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.     

Toward a model of socializing project team members: An integrative approach

Project work is becoming more and more important in everyday business, as is staffing the right newcomers for the project. Recognizing that not all new project team workers possess equally important specific knowledge, skills and abilities for the success of projects, we draw on project management, human resource management, and organizational socialization literature to develop a framework on how new project team members might be socialized, depending on their strategic value for the project. We specifically draw on the socialization tactics literature and propose how four categories of new employees – Internal specialists, External specialists, External generalists and Internal generalists; based on two dimensions – work task complexity and employment mode, can be socialized more effectively. Implications for theory and practice are discussed as well.     

Structural and electrical properties of Cr-doped SrTiO3 porous materials

Series of single-phase materials with assumed formula SrTi_1?xCr_xO₃ (where x = 0, 1, 4, 6 mol.%) were obtained by sol-gel method. The structure and microstructure of materials were characterised by X-ray diffraction and scanning electron microscopy methods. Moreover, the study of electrical properties and evaluation of chemical stability in CO₂/H₂O atmosphere was performed by electrochemical impedance spectroscopy and thermogravimery methods, respectively. The possibility of participation of Cr-doped strontium titanate in oxidation–reduction processes was analysed by temperature-programed reduction (TPR) and temperature-programed oxidation (TPOx) measurements. The changes of lattice parameters together with XPS analysis, the Seebeck coefficient measurements results and TPR profiles obtained for SrTi_1?xCr_xO₃ materials prove the presence of chromium on +3 and +6 oxidation stages. Thus, chromium can be treated as both acceptor- and donor-type dopant in the SrTiO₃ structure. The Cr³⁺/Cr⁶⁺ ratio strongly affects the electrical properties, as the change of conduction mechanism was observed. The results of performed stability test clearly indicate that incorporation of chromium into SrTiO₃ structure results with decrease of chemical stability in CO₂ atmosphere.     

Fast periocular authentication in handheld devices with reduced phase intensive local pattern

To ensure highest security in handheld devices, biometric authentication has emerged as a reliable methodology. Deployment of mobile biometric authentication struggles due to computational complexity. For a fast response from a mobile biometric authentication method, it is desired that the feature extraction and matching should take least time. In this article, the periocular region captured through frontal camera of a mobile device is considered under investigation for its suitability to produce a reduced feature that takes least time for feature extraction and matching. A recently developed feature Phase Intensive Local Pattern (PILP) is subjected to reduction giving birth to a feature termed as Reduced PILP (R-PILP), which yields a matching time speed-up of 1.56 times while the vector is 20% reduced without much loss in authentication accuracy. The same is supported by experiment on four publicly available databases. The performance is also compared with one global feature: Phase Intensive Global Pattern, and three local features: Scale Invariant Feature Transform, Speeded-up Robust Features, and PILP. The amount of reduction can be varied with the requirement of the system. The amount of reduction and the performance of the system bears a trade-off. Proposed R-PILP attempts to make periocular suitable for mobile devices.     

Structural and optical characterization of CuInSe2 films deposited by hot wall vacuum evaporation method

Copper indium diselenide (CuInSe₂) compound was prepared by direct reaction of high-purity elemental copper, indium and selenium. CuInSe₂ thin films were deposited onto well-cleaned glass substrates by a hot wall deposition technique using quartz tubes of different lengths (0.05, 0.07, 0.09, 0.11 and 0.13 m). X-ray diffraction studies revealed that all the deposited films are polycrystalline in nature and exhibit chalcopyrite structure. The crystallites were found to have a preferred orientation along the (1 1 2) direction. Micro-structural parameters of the films such as grain size, dislocation density, tetragonal distortion and strain have been determined. The grain sizes in the films were in the range of 65-250 nm. As the tube length increases up to 0.11 m the grain size in the deposited films increases, but the strain decreases. The film deposited using the 0.13 m long tube has smaller grain size and more strain. CuInSe₂ thin films coated using a tube length of 0.11 m were found to be highly crystalline when compared to the films coated using other tube lengths; it has also been found that films possess the same composition (Cu/In=1.015) as that of the bulk. Scanning electron microscope analysis indicates that the films are polycrystalline in nature. Structural parameters of CuInSe₂ thin films deposited under higher substrate temperatures were also studied and the results are discussed. The optical absorption coefficient of CuInSe₂ thin films has been estimated as 10⁴ cm⁻¹ (around 1050 nm). The direct band gap of CuInSe₂ thin films was also determined to be between 1.018 and 0.998 eV.