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Investigation of the anticancer potential of newly synthesized N4-substituted thiosemicarbazones: In silico and in vitro biological approaches
No full textFour thiosemicarbazones by using tolualdehyde and cuminaldehyde having the formula, R2−(S)C−HN−NHC−R1[R1 = CH3 & R2 = C4H9N (TAP), R2 = C4H9NO & R1 = CH3 & (TAM), R2 = C4H9N & R1 = (CH3)2CH (CMP), R2 = C4H9NO & R1 = (CH3)2CH (CMM)] have been synthesized. The compound interactions were assessed using their UV−visible, infrared, NMR, and HRMS spectra. Single−crystal X−ray diffraction was employed to know the molecular structure of CMP and TAP. The compounds were assessed for their interactions with Calf−Thymus (CT)−DNA using spectroscopic titrations using both emission and absorption spectra. As per the research findings on DNA binding, the compounds interactively interacted with DNA, as indicated by the hypochromic and slight red shift. TAP exhibited a high binding constant (5.16 × 105), suggesting a stronger binding to CT−DNA compared to other compounds. The fluorescence titration spectra of BSA binding experiments exhibited a noteworthy hypochromic shift and red shift, displaying a strong interaction of chemicals with BSA. EGFR protein docking examination demonstrated the potential of compounds to treat the targets. TAP displayed the highest binding score (–6.4230 Kcal/mol) to EGFR with the four compounds. To compute density functional theory (DFT), B3LYP/6−311 G (d, p) level theories have been implemented. Generated compounds' computational analyses reveal the structural stability of compound TAP than the rest synthesized ligands. SwissADME investigations indicate that the LogP values for each compound are less than five indicating that they have the right lipophilicity characteristics. All newly synthesized compounds follow Lipinski's rule of drug lines. A good result for this characteristic is indicated by the low degree of synthetic accessibility, which falls between two and three. Each of the compounds (TAP−CMM) can develop into a viable oral medicine. Each compound (TAP−CMM) was tested for its anticancer potential using MCF−7, MCF−10A, A549, and human HepG−2 liver. TAP demonstrated favorable efficacy in HepG−2 liver cancer cells, exhibiting IC50 values of 23.1 μM
Towards Genetically Informed Conservation of the Bardoka and Karakachan Sheep Breeds Autochthonous to Serbia
No full textBardoka and Karakachan sheep are primitive regional transboundary Pramenka-type sheep autochthonous to the Balkan Peninsula, whose populations have been reduced to a critically small size in Serbia. We genotyped 105 Bardoka animals (97 ewes and 8 rams from three flocks) and 97 Karakachan sheep (86 ewes and 11 rams from four flocks), along with 28 Ile-de-France (IDF) animals used for a comparison (25 ewes and 3 rams), using 14 nuclear microsatellites to assess their genetic status and establish a foundation for their genetically informed conservation. We utilized genetic data to assess inbreeding values of individuals (I) and pairwise relatedness (r) traditionally inferred from the pedigree data, which are incomplete in the studied autochthonous breeds. We used these data to assemble a data set of unrelated individuals for subsequent genetic analyses. Low but statistically significant genetic differentiation of Bardoka and Karakachan sheep (FST = 0.031, p < 0.01) demonstrates that these phenotypically distinct breeds differ at the genetic level as well. The I and r in ewes were higher in the Karakachan sheep (I = 0.09, r = 0.07) than in Bardoka (I = 0.06, r = 0.06). Contrary to the IDF rams, Bardoka and Karakachan sheep rams were genetically heterogeneous and those of the latter breed displayed higher average r values (0.01 vs. 0.08, respectively). Rams of both local breeds had identical I values of 0.02. Although Bardoka and Karakachan sheep still harbor rather high levels of genetic diversity (HE = 0.761 ± 0.028 and 0.761 ± 0.021, respectively), the overall genetic data demonstrate that the genetic consequences of the population decline were more severe in the latter breed. A genetic structure presenting a general trend of differentiation of flocks with low genetic exchange into separate genetic entities was observed, indicating the effects of genetic drift. The implementation of the genetically informed conservation, together with the ongoing efforts of the state to enlarge the Bardoka and Karakachan sheep populations, would increase the prospects for the long-term survival of both breeds in Serbia
Phenolics over Zeolites and Related Materials—Biomedical and Environmental Applications
No full textThis work analyzes the following two aspects of zeolite applications: their application as carriers in delivery systems for phenolics applied as antioxidants or anticancer agents and the efficient removal of phenolic compounds from aqueous environments. The dual role of zeolites in increasing antioxidant bioavailability and environmental remediation is summarized, and perspectives on progress in zeolite adaptable applications are given. Special attention is given to theoretical methods that will guide future advanced delivery systems for biomedical applications, as well as serve as a focal point in designing multipurpose materials for comprehensive environmental solutions. Perspectives in both fields are discussed
A Multi-Spectroscopic and Molecular Docking Analysis of the Biophysical Interaction between Food Polyphenols, Urolithins, and Human Serum Albumin
No full textSecondary polyphenol metabolites, urolithins (UROs), have anti-oxidative, anti-inflammatory, and antidiabetic properties. Therefore, their biological activity relies on blood transport via human serum albumin (HSA) and tissue distribution. The main goal we set was to investigate the interaction between HSA and different URO (URO A, URO B, URO C, URO D, and glucuronidated URO A and B) using a combination of multi-spectroscopic instrumental and in silico approaches. The fluorescence spectroscopy revealed that URO can quench the naturally occurring fluorescence of HSA in a concentration-dependent manner. The HSA fluorescence was quenched by both a static and dynamic mechanism. The results showed that free UROs bind to HSA with higher affinity than their conjugated forms. CD spectroscopy and FTIR revealed that the alpha-helical structure of HSA is preserved. The calculated Gibbs free energy change indicates that the URO–HSA complex forms spontaneously. There is a single binding site on the HSA surface. The molecular docking results indicated that unconjugated Uro binds to Sudlow I, while their conjugation affects this binding site, so in the conjugated form, they bind to the cleft. Docking experiments indicate that all UROs are capable of binding to both thyroxine recognition sites of ligand-bound HSA proteins. Examining interactions under the following conditions (298 K, 303 K, and 310 K, pH 7.4) is of great importance for determining the pharmacokinetics of these bioactive compounds, as the obtained results can be used as a basis for modulating the potential dosing regimen
Gait Characteristics during Dual-Task Walking in Elderly Subjects of Different Ages
Get PDFBackground: In older age, walking ability gradually decreases due to factors including impaired balance, reduced muscle strength, and impaired vision and proprioception. Further, cognitive functions play a key role during walking and gradually decline with age. There is greater variability in gait parameters when the demands during walking increase, in dual- and multiple-task situations. The aim of this study was to analyze gait parameters while performing a demanding cognitive and motor dual task in three different age-related healthy elderly subject groups. Method: A total of 132 healthy individuals (54 males, 78 females) were divided into three groups—55 to 65, 66 to 75, and 76 to 85 years. The subjects performed a basic walking task, dual motor task, dual mental task, and combined motor and mental task while walking. The gait parameters cycle time, stride length, swing time, and double support time were noted, as well as the variability of those parameters. Results: Cycle time was longer and stride length was shorter in the >76-year-old group than in the 51–65-year-old group in all test conditions. A comparison of all three groups did not show a significant difference in swing time, while double support time was increased in the same group. Conclusions: Changes are observed when gait is performed simultaneously with an additional motor or cognitive task. Early detection of gait disorders can help identify elderly people at increased risk of falls. Employing a dual-task paradigm during gait assessment in healthy elderly subjects may help identify cognitive impairment early in the course of the disturbance
Revealing profile of cancer-educated platelets and their factors to foster immunotherapy development
Get PDFAmong multiple hemostasis components, platelets hyperactivity plays major roles in cancer progression by providing surface and internal components for intercellular crosstalk as well as by behaving like immune cells. Since platelets participate and regulate immunity in homeostatic and disease states, we assumed that revealing platelets profile might help in conceiving novel anti-cancer immune-based strategies. The goal of this review is to compile and discuss the most recent reports on the nature of cancer-associated platelets and their interference with immunotherapy. An increasing number of studies have emphasized active communication between cancer cells and platelets, with platelets promoting cancer cell survival, growth, and metastasis. The anti-cancer potential of platelet-directed therapy has been intensively investigated, and anti-platelet agents may prevent cancer progression and improve the survival of cancer patients. Platelets can (i) reduce antitumor activity; (ii) support immunoregulatory cells and factors generation; (iii) underpin metastasis and, (iv) interfere with immunotherapy by expressing ligands of immune checkpoint receptors. Mediators produced by tumor cell-induced platelet activation support vein thrombosis, constrain anti-tumor T- and natural killer cell response, while contributing to extravasation of tumor cells, metastatic potential, and neovascularization within the tumor. Recent studies showed that attenuation of immunothrombosis, modulation of platelets and their factors have a good perspective in immunotherapy optimization. Particularly, blockade of intra-tumoral platelet-associated programmed death-ligand 1 might promote anti-tumor T cell-induced cytotoxicity. Collectively, these findings suggest that platelets might represent the source of relevant cancer staging biomarkers, as well as promising targets and carriers in immunotherapeutic approaches for combating cancer
Role of Arthrospira Platensis in Preventing and Treating High-Fat Diet-Induced Hypercholesterolemia in Adult Rats
No full textHyperlipidaemia is a recognised risk factor for cardiovascular disease. In this study, the antihyperlipidaemic properties of spirulina (Arthrospira platensis, strain S2 from Serbia) were tested in adult Wistar rats before and after induction of hypercholesterolaemia by a high-fat diet (HFD) to compare the preventive with the curative effect. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured in the blood samples. The chemical composition (lipids, proteins and cholesterol) and the content of bile acids in the faeces of the animals were also analysed. Feeding rats with an atherogenic diet for 10 weeks led to the successful development of hyperlipidaemia, as serum TC and LDL-C levels as well as lipids, cholesterol and bile acids in the animals’ faeces were significantly increased. Pre- and post-treatment with spirulina led to a reduction in serum LDL, TC and ALT levels. Administration of spirulina resulted in both a significant increase in primary bile acids excretion and a decrease in bile acids metabolism, with pre-treatment being more effective than post-treatment in some cases. These results suggest that increased excretion of bile acids as well as an effect on the gut microbiota may be the mechanism responsible for the anti-hyperlipidaemic activity of the tested spirulina strain
Myeloid-derived suppressor cells: Implication in myeloid malignancies and immunotherapy
No full textMyeloid malignancies stem from a modified hematopoietic stem cell and predominantly include acute myeloid leukemia, myelodysplastic neoplasms, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid-derived suppressor cells (MDSCs) exhibit immunoregulatory properties by governing the innate and adaptive immune systems, creating a permissive and supportive environment for neoplasm growth. This review examines the key characteristics of MDSCs in myeloid malignancies, highlighting that an increased MDSC count corresponds to heightened immunosuppressive capabilities, fostering an immune-tolerant neoplasm microenvironment. Also, this review analyzes and describes the potential of combined cancer therapies, focusing on targeting MDSC generation, expansion, and their inherent immunosuppressive activities to enhance the efficacy of current cancer immunotherapies. A comprehensive understanding of the implications of myeloid malignancies may enhance the exploration of immunotherapeutic strategies for their potential application
Activated charcoal as a carrier of probiotics: A new approach for pathogen elimination in wounds
No full textAntibiotic resistance isone of the biggest threats to global health, food securityand development today[1].However, development of conventional anti-infective drugs is going slowly, so new innovative strategies and more research are urgently needed in identifying, developing, implementing and evaluating novel therapies for antibiotic-resistant infections.The two-year ProHealingAC project, funded by the Science Fundof theRepublicof Serbia, aims to use beneficial properties of ACand probiotic microorganisms in developing anew strategy for prevention and localtreatment of antibiotic-resistant infections in wounds. Previously, it has been shown that activated charcoal (AC) in conjunction with different active agents has an efficient antimicrobial activity [2,3]. The aimof this projectis to develop biocomposites (BCs) based on AC fabric, as adsorptive component, and probiotics, as bioactive component in order to achieve their synergetic activity forefficient and sustained localdelivery of bioactive agents directly into the woundarea.Also, special attention has been given to the influence of glucose level (normo-and hyperglycemia) in the microenvironment of the wound
