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Background: Chemoresistance of cancer cells, resulting from various mechanisms, is a significant obstacle to the effectiveness of modern cancer therapies. Targeting fibroblast growth factors (FGFs) and their receptors (FGFRs) is becoming crucial, as their high activity significantly contributes to cancer development and progression by driving cell proliferation and activating signaling pathways that enhance drug resistance. Methods: We investigated the potential of honokiol and FGF ligand trap in blocking the FGF1/FGFR1 axis to counteract drug resistance. Using PEAQ-ITC, we verified direct interaction of honokiol with the FGFR1 kinase domain. We then demonstrated the effect of FGF1/FGFR1 inhibition on taltobulin resistance in cells expressing FGFR1. Finally, we generated drug-resistant clones by prolonged exposure of cells with negligible FGFR levels to taltobulin alone, taltobulin and honokiol, or taltobulin and FGF ligand trap. Results: We demonstrated for the first time a direct interaction of honokiol with the FGFR1 kinase domain, resulting in inhibition of downstream signaling pathways. We revealed that both honokiol and FGF ligand trap prevent FGF1- dependent protection against taltobulin in cancer cells expressing FGFR1. In addition, we showed that cells obtained by long-term exposure to taltobulin are resistant to both taltobulin and other microtubule-targeting drugs, and exhibit elevated levels of FGFR1 and cyclin D. We also found that the presence of FGFligand trap prevents the development of long-term resistance to taltobulin. Conclusion: Our results shed light on how blocking the FGF1/FGFR1 axis by honokiol and FGF ligand trap could help develop more effective cancer therapies, potentially preventing the emergence of drug-resistant relapses. [ABSTRACT FROM AUTHOR]

There are many scientific reports on the interaction of the SARS‐CoV‐2 virus S protein (and its RBD) with the human ACE2 receptor protein. However, there are no reliable data on how this interaction differs from the interaction of the receptor binding domain of SARS‐CoV‐1 with ACE2, in terms of binding strength and changes in reaction enthalpy and entropy. Our studies have revealed these differences and the impact of zinc ions on this interaction. Intriguingly, the binding affinity of both RBDs (of SARS‐CoV‐1 and of SARS‐CoV‐2) to the ACE2 receptor protein is almost identical; however, there are some differences in the entropic and enthalpic contributions to these interactions. [ABSTRACT FROM AUTHOR]

The article discusses the importance of a holistic, multidisciplinary approach to medicine in understanding and treating health problems. It emphasizes the value of collaboration between researchers from different fields, as their unique perspectives and methods can lead to innovative solutions and breakthroughs. The article also highlights the significance of ethical considerations in research, particularly when studying humans or populations. The MRTBS2024 conference is mentioned as an event that brings together scientists from various disciplines and cultural backgrounds to promote a comprehensive understanding of health and encourage collaboration on research projects. The project is co-financed by the state budget under the Excellent Science II Program. [Extracted from the article]

Introduction: Mercury is a heavy metal commonly found in the environment and many food products due to pollution. It can enter the human body through dental procedures, such as caries restoration using dental amalgam or wearing orthodontic appliances. Dietary habits can influence mercury intake in daily life. The toxic effects of mercury manifest neurologically, causing issues with concentration, walking, insomnia, and more. The human body eliminates mercury by incorporating it into nail and hair structures, making them effective indicators for monitoring mercury levels in the body. Aim: The aim of the study was to determine mercury levels in hair and nails samples of individuals to verify the correlation between them. The study also examined the possible influence of dietary behaviors and dental history on mercury levels in the material. Material and methods: Hair and nail samples were collected from patients using certified mercury-free equipment. The samples were weighed (Radwag, Poland) and total mercury levels were determined using an AMA 254 analyzer (Altec, Czech Republic). Results: The study revealed a strong correlation between hair and nail samples. Additionally, the average mercury level was higher in women than in men. no correlation was found between orthodontic procedures and mercury content in samples. Among men who frequently consumed fish and are physical active several times a week, the highest mercury levels were noted. The mercury content in the hair of past smokers was higher than the median for both groups. Conclusions: The results of the preliminary studies confirm the influence of fish consumption on mercury levels in the body as a more significant factor than gender and age. Further research should be conducted on a larger group of patients to more accurately determine the impact of daily behaviors on possible mercury adsorption and accumulation, which can have a significant toxic effect on human health. [ABSTRACT FROM AUTHOR]

Introduction: Bioactive peptides can have various positive effects, such as the prevention of diseases or the modulation of physiological systems. For our research, we selected four peptides identified in kombucha-treated milk extracts that have been shown to have a strong antihypertensive effect, as well as two histatins (Hst5 and Hst8) that have an antimicrobial effect. Their interactions with Cu(II) metal ions were investigated using isothermal titration microcalorimetry (ITC) and UV-Vis techniques. In addition, the antimicrobial activity of these peptides against C. albicans, S.aureus and E. coli, an opportunistic human pathogens, was investigated. C. albicans causes mucosal and systemic infections in susceptible individuals and E. coli is involved in various intestinal and extra-intestinal infections. Aim: The aim of our work was to investigate the interactions of peptides with potential biological activity with Cu(II) ions and their influence on C. albicans S. aureus and E. coli growth. Material and methods: The affinity of the metal-peptide interaction and the changes in enthalpy and entropy were studied using the ITC technique. The UV-Vis technique was used to characterize the formation of Cu (II) complexes wiTheach of the peptides studied. All these experiments were performed at a pH around 6 to mimic the pH of human skin. The microbiological studies were performed using the dilution susceptibility testing method in Sabouraud Dextrose liquid medium and Mueller-Hinton medium (MH). Results: All peptides: AVPQEVLNENLLR, YLQGSNLVVPLTDD, KFKGFVEPFPAVE, FVAPEPFVFGKEK, DSHAKRHHGYKRKFHEKHHSHRGY, KFHEKHHSHRGY (named by us Pep1-Pep4, Hst5 and Hst8 respectively) bind Cu (II) ions with quite high affinity (Kd in the range of 35-92 μM). All reactions were endothermic and entropy-driven. A microbiological assay showed that Pep3 and Pep4 have an inhibitory effect on E. coli by binding Cu(II) ions. Pep4 also has inhibit influence of S. aureus growth. In addition, Hst5 and Hst8 with the addition of Cu(II) inhibit the growth of C. albicans and E. coli to a small extent. Conclusions: Peptides 3 and 4 as well as histatin 8 have potential, as they have a slightly inhibitory effect on the microorganisms C. albicans, S. aureus and E. coli. They therefore represent material for planning further research with them and their analogues designed by us in the future. [ABSTRACT FROM AUTHOR]

Introduction: Heat shock proteins (HSPs) are synthesized in cells upon an increase in temperature, but also contribute to cell protection in various ways. In addition, crystallins, which belong to the family of small HSPs, are present in the eye lens and the polymer structures they form are responsible for the transparency of the lens and its protection at high temperatures. Since the interaction of crystallin with metal ions such as zinc or copper could be crucial for the maintenance of these properties, it is worthwhile to determine the binding sites of metal ions and the stability of such complexes. Since these proteins polymerize easily, a simpler way to study them is to examine their peptide fragments and their analogs. Aim: The aim of the studies was to identify metal ion-binding groups in the investigated peptides. Material and methods: We investigated the coordination properties of selected peptides developed on the basis of native fragments of α-B-crystallin (a similar fragment is present in α-A-crystallin). Different methods such as potentiometric titration, isothermal calorimetric titration (ITC) and spectrophotometric methods (UV-Vis or CD titration) were used to determine the physicochemical properties of the studied peptides and to characterize the coordination properties with copper and zinc ions. Results: We identified the main residues involved in the binding of metal ions (namely His-131 and Glu-126) and determined the stability constants and thermodynamic properties of the copper and zinc complexes of the studied systems. Conclusions: The results show that the potential binding sites in the protein are His and Glu residues. Changes in the protein structure, including deletion or substitution of these residues, may lead to disruption or loss of the ability to bind metal ions and consequently to a loss of protection against clouding of the crystalline lens. [ABSTRACT FROM AUTHOR]

Primary immunodeficiency diseases (PIDs) are genetic based disorders which lead to the dysfunction of the immune system. There are persistent and recurrent infections within PID patient due to cellular and humoral immunity impairment. The most common infections are caused by Salmonella Enteritidis, Shigella flexneri, Mycobacterium avium complex, Toxoplasma gondii, CMV, Candida albicans, Cryptococcus neoformans or Pneumocystis jiroveci. These infections have a severe course of disease with limited treatment in a conventional way. Full patient recovery after intensive and long-term therapy is often impossible. Viral infections in PID patients are equally frequent. The incidences of Herpesviridae and HCV infections are the same for PID patients and healthy people. However, the infections may have worse course of disease and leave more destruction in the body. Enteroviral infections occur despite the antibodies supplementation; they spread spontaneously throughout the body, also affecting the central nervous system. Skin, nails and mucous membranes infections are equally persistent problems caused by fungi, mainly Candida genus. Infections with these pathogens are often accompanied by hormonal disorders and immunosuppressive therapy. Sepsis and mixed infections are definitely the most dangerous for patients with infections. Infections occur most often in the first years of the child's life, when the body has not developed yet a fully functioning immunity system. The diagnosis of PNO in infants may be difficult due to the presence of antibodies from mother and the similarity of the symptoms of infectious diseases and common infections. [ABSTRACT FROM AUTHOR]

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