Tribological and Antimicrobial Properties of Two-Component Self-Assembled Monolayers Deposited on Ti-Incorporated Carbon Coatings.

In this work, Ti-incorporated carbon coatings were used as substrates for modification with one- and two-component self-assembled monolayers of organosilane compounds using a polydimethylsiloxane (PDMS) stamp. This enabled the selective functionalization of surfaces with micrometric dimensions. The topography of the modified surfaces was defined using an atomic force microscope (AFM). The effectiveness of the modification was confirmed by measurements of the water contact angle and surface free energy using the Oss and Good method. Using a T-23 microtribometer with counterparts in the shape of balls that were made of steel, silicon nitride (Si3N4), and zirconium dioxide (ZrO2), the tribological properties of the obtained coatings were tested. These investigations showed that modification by using a PDMS stamp makes it possible to produce two-component ultrathin silane layers on Ti-containing carbon substrates. Two-component organosilane layers had higher hydrophobicity, a lower friction coefficient, and a smaller width of wear tracks than the one-component analogs. It was also found that the work of adhesion of the created surfaces had a significant influence on the value of the friction coefficient and the percentage value of the growth inhibition of bacteria.

The Role of the CD28 Family Receptors in T-Cell Immunomodulation.

The CD28 family receptors include the CD28, ICOS (inducible co-stimulator), CTLA-4 (cytotoxic T-lymphocyte antigen-4), PD-1 (programmed cell death protein 1), and BTLA (B- and T-lymphocyte attenuator) molecules. They characterize a group of molecules similar to immunoglobulins that control the immune response through modulating T-cell activity. Among the family members, CD28 and ICOS act as enhancers of T-cell activity, while three others-BTLA, CTLA-4, and PD-1-function as suppressors. The receptors of the CD28 family interact with the B7 family of ligands. The cooperation between these molecules is essential for controlling the course of the adaptive response, but it also significantly impacts the development of immune-related diseases. This review introduces the reader to the molecular basis of the functioning of CD28 family receptors and their impact on T-cell activity.

Peptides targeting the BTLA-HVEM complex can modulate T cell immune response.

Immune checkpoints secure the proper function of the immune system and the maintenance of the BTLA-HVEM complex, an inhibitory immune checkpoint, is one of the pathways vital for T cell responsiveness to various stimuli. The present study reports the immunomodulatory potential of five peptides targeting the BTLA-HVEM complex on the activity of human T cells. Isolated T cells were exposed to the peptides alone or combined with CD3/CD28 mAb for 72 h or 120 h. The flow cytometry was used to evaluate the activation markers (CD69, CD62L, CD25), changes within the T cell memory compartment, proliferation rate, and apoptosis of T cells. The immunomodulatory effect of the peptides was visible as an increase in the percentage of CD4+ and CD8+ T cells expressing CD69 or CD25, a boost in T cell proliferation, and shifts in the T cell memory compartment. Pep(2) and Pep(5) were the most promising compounds, displaying a putative immune-restoring function.

The Synergistic Effect of Biosynthesized Silver Nanoparticles and Phytocompound as a Novel Approach to the Elimination of Pathogens.

Due to the wide applications of silver nanoparticles (AgNPs), research on their ecological synthesis has been extensive in recent years. In our study, biogenic silver nanoparticles were synthesized extracellularly using the white rot fungus Trametes versicolor via two cultivation methods: static and shaking. The cell filtrate of the fungus was used as a reducing agent in the process of nanoparticle synthesis. Characterization of the obtained nanoparticles was carried out using UV-VIS spectroscopy and scanning electron microscopy. The biosynthesized nanoparticles have antimicrobial potential against pathogenic bacteria, particularly in Gram-negative strains. The bactericidal effect was obtained for E. coli at a concentration of 7 µg/mL. The use of higher concentrations of compounds was necessary for Gram-positive bacteria. Taking into account the problem of the risk of cytotoxicity of AgNPs, combined therapy using a phytochemical was used for the first time, which was aimed at reducing the doses of nanoparticles. The most representative synergistic effect was observed in the treatment of 5 µg/mL silver nanoparticles in combination with 15 µg/mL ursolic acid against E. coli and P. aeruginosa with a bactericidal effect. Moreover, the coadministration of nanoparticles considerably reduced the growth of both Staphylococcus strains, with a bactericidal effect against S. aureus. The viability test confirmed the strong synergistic effect of both tested compounds. Silver nanoparticles synthesized using the T. versicolor showed excellent antibacterial potential, which opens perspectives for future investigations concerning the use of the nanoparticles as antimicrobials in the areas of health.

Optimizing the microbial synthesis of silver nanoparticles using Gloeophyllum striatum and their antimicrobial potential evaluation.

The search for new sources of silver nanoparticles (AgNPs) is highly relevant in many fields. Mycosynthesis seems to be advantageous for large-scale production, and using brown rot fungi might be a promising solution. In this study, AgNP synthesis using Gloeophyllum striatum DSM 9592 was performed under various process conditions. The resulting AgNPs were characterized using UV/Vis, FT-IR, SEM and NTA techniques and their biological activities were determined. It was found that different synthesis conditions changed the production efficiency, which was the highest in 28 s AgNPs. Moreover, temperature and shaking conditions slightly affected the activity of the resulting AgNP types. Gram-negative bacteria were generally more susceptible to the action of AgNPs with MIC values two- or three-fold lower compared to Gram-positive strains. Pseudomonas aeruginosa was the most sensitive among tested strains with a MIC value of 1.56 µg/ml. The research was additionally extended by the biofilm formation assay for this strain. It was found that AgNPs of all types led to a reduction in biofilm-forming capability of P. aeruginosa over the tested concentration range. Haemolytic and cytotoxic activity assays showed that synthesis conditions also affected AgNP toxicity. For instance, 4 ns AgNPs were the least cytotoxic and cause less than 50% reduction of fibroblast viability in the concentration that inhibits the growth of P. aeruginosa completely. These results highlight the possible utility of mycogenic silver nanoparticles as an antibacterial agent in antiseptics or other external treatments.

Chemokines and Cytokines Profiles in Patients with Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis: A Preliminary Study.

The damage to small vessels in AAV and inflammatory reactions are accompanied by the release of various chemokines and cytokines. Using a flow cytometry technique, we assessed the levels of specific cytokines, namely IL-1ß IL-6, IL-8, IL-10, IL12p70, and TNF, and chemokines, IFN-α, IP-10, and MIG in the serum from 9 healthy volunteers and 20 AAV patients, where 11 of the patients were not treated and evaluated at the time of diagnosis and 9 were already diagnosed and taking CY + GCS. The obtained results were then compared considering the activity of the disease, the type and titre of the ANCA antibodies, the inflammatory status, and the kidneys' condition. Amongst others, the IL-6, IL-8, IL-10, TNF, and MIG levels were much higher in the serum of AAV patients than in healthy controls, whereas the level of IL-1ß was higher in healthy volunteers. Additionally, the levels of IL-6, IL-10, IP-10, and MIG negatively correlated with the eGFR level, while the level of IFN-α positively correlated with the titre of PR3-ANCA. As most of the molecules are implicated in trafficking primed neutrophils towards small vessels, looking for links between the levels of these cytokines/chemokines and the clinical symptoms of AAV may facilitate the diagnosis and predict the progression of the disease.

The immunomodulatory effect of lithium as a mechanism of action in bipolar disorder.

Bipolar disorder (BD) is a chronic mental disorder characterized by recurrent episodes of mania and depression alternating with periods of euthymia. Although environmental and genetic factors have been described, their pathogenesis is not fully understood. Much evidence suggests a role for inflammatory mediators and immune dysregulation in the development of BD. The first-line treatment in BD are mood-stabilizing agents, one of which is lithium (Li) salts. The Li mechanism of action is not fully understood, but it has been proposed that its robust immunomodulatory properties might be one of the mechanisms responsible for its effectiveness. In this article, the authors present the current knowledge about immune system changes accompanying BD, as well as the immunomodulatory effect of lithium. The results of studies describing connections between immune system changes and lithium effectiveness are often incoherent. Further research is needed to understand the connection between immune system modulation and the therapeutic action of lithium in BD.

Biodegradable Chitosan-Based Films as an Alternative to Plastic Packaging.

The impact of synthetic packaging on environmental pollution has been observed for years. One of the recent trends of green technology is the development of biomaterials made from food processing waste as an alternative to plastic packaging. Polymers obtained from some polysaccharides, such as chitosan, could be an excellent solution. This study investigated the biodegradability of chitosan-metal oxide films (ZnO, TiO2, Fe2O3) and chitosan-modified graphene films (CS-GO-Ag) in a soil environment. We have previously demonstrated that these films have excellent mechanical properties and exhibit antibacterial activity. This study aimed to examine these films' biodegradability and the possibility of their potential use in the packaging industry. The obtained results show that soil microorganisms were able to utilize chitosan films as the source of carbon and nitrogen, thus providing essential evidence about the biodegradability of CS, CS:Zn (20:1; 10:1), and CS:Fe2O3 (20:1) films. After 6 weeks of incubation, the complete degradation of the CS-Fe2O3 20:1 sample was noted, while after 8 weeks, CS-ZnO 20:1 and CS-ZnO 10:1 were degraded. This is a very positive result that points to the practical aspect of the biodegradability of such films in soil, where garbage is casually dumped and buried. Once selected, biodegradable films can be used as an alternative to plastic packaging, which contributes to the reduction in pollution in the environment.

Antimicrobial Activity and Toxicity of Newly Synthesized 4-[4-(benzylamino)butoxy]-9H-carbazole Derivatives.

One of the main challenges of medicinal chemistry is the search for new substances with antimicrobial potential that could be used in the fight against pathogenic microorganisms. Therefore, the antimicrobial activity of newly synthesized compounds is still being investigated. Carbazole-containing compounds appear to be promising antibacterial, antifungal, and antiviral agents. The aim of this study was to examine the antimicrobial potential and toxicity of newly synthesized isomeric fluorinated 4-[4-(benzylamino)butoxy]-9H-carbazole derivatives. Their antimicrobial activity against bacteria and fungi was tested according to CLSI guidelines. Similarly to previously studied carbazole-containing compounds, the tested derivatives showed the ability to effectively inhibit the growth of Gram-positive bacteria. The addition of carbazole derivatives 2, 4, and 8 at the concentration of 16 µg/mL caused the inhibition of S. aureus growth by over 60%. The MIC value of compounds 2-5 and 7-10 was 32 µg/mL for Staphylococcus strains. Gram-negative strains of E. coli and P. aeruginosa were found to be more resistant to the tested carbazole derivatives. E. coli cells treated with compounds 3 and 8 at a concentration of 64 µg/mL resulted in a greater-than-40% reduction in bacterial growth. In the case of the P. aeruginosa strain, all compounds in the highest concentration that we tested limited growth by 35-42%. Moreover, an over-60% inhibition of fungal growth was observed in the cultures of C. albicans and A. flavus incubated with 64 µg/mL of compounds 2 or 7 and 1 or 4, respectively. The hemolysis of red blood cells after their incubation with the tested carbazole derivatives was in the range of 2-13%. In the case of human fibroblast cells, the toxicity of the tested compounds was higher. Derivative 1, functionalized with fluorine in position 2 and its hydrobromide, was the least toxic. The obtained results indicated the antimicrobial potential of the tested 4-[4-(benzylamino)butoxy]-9H-carbazole derivatives, especially against S. aureus strains; therefore, it is worth further modifying these structures, in order to enhance their activity against pathogenic microorganisms.

Impact of Vitamin D on Immunopathology of Hashimoto's Thyroiditis: From Theory to Practice.

Hashimoto's thyroiditis (HT) is a common autoimmune disease affecting the thyroid gland, characterized by lymphocytic infiltration, damage to thyroid cells, and hypothyroidism, and often requires lifetime treatment with levothyroxine. The disease has a complex etiology, with genetic and environmental factors contributing to its development. Vitamin D deficiency has been linked to a higher prevalence of thyroid autoimmunity in certain populations, including children, adolescents, and obese individuals. Moreover, vitamin D supplementation has shown promise in reducing antithyroid antibody levels, improving thyroid function, and improving other markers of autoimmunity, such as cytokines, e.g., IP10, TNF-α, and IL-10, and the ratio of T-cell subsets, such as Th17 and Tr1. Studies suggest that by impacting various immunological mechanisms, vitamin D may help control autoimmunity and improve thyroid function and, potentially, clinical outcomes of HT patients. The article discusses the potential impact of vitamin D on various immune pathways in HT. Overall, current evidence supports the potential role of vitamin D in the prevention and management of HT, although further studies are needed to fully understand its mechanisms of action and potential therapeutic benefits.

The Immunomodulatory Effect of Nigella sativa.

BACKGROUND: For thousands of years till nowadays, Nigella sativa (NS) has served as a common spice and food preservative. Its seed extracts, seed oil, and essential oil in traditional medicine have been used to remedy many ailments such as headaches, fever, gastric complaints, and even rheumatism. In addition, the antibacterial, virucidal, fungicidal, and antiparasitic properties of NS are well known. However, studies on the possible immunomodulatory effects of black cumin are relatively scarce. This article discusses in vitro and in vivo research supporting the immunomodulatory role of NS. METHODS: The review is based on articles, books, and conference papers printed until September 2022, found in the Web of Science, PubMed, Wiley Online Library, and Google Scholar databases. RESULTS: Experimental findings were reported concerning the ability of NS to modulate inflammation and immune responses or cytotoxic activity. CONCLUSIONS: All results suggest that NS can potentially be employed in developing effective therapeutic agents for regulating immune reactions.

The Impact of Nigella sativa Essential Oil on T Cells in Women with Hashimoto's Thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disease mediated by T cells. It is characterized by the presence of thyroid autoantibodies in the serum, such as anti-thyroid peroxidase antibodies (TPO-Ab) and anti-thyroglobulin antibodies (TG-Ab). The essential oil extracted from Nigella sativa seeds is rich in bioactive substances, such as thymoquinone and cymene. METHODS: Therefore, we examined the effect of essential oil from Nigella sativa (NSEO) on T cells from HT patients, especially their proliferation capacity, ability to produce cytokines, and susceptibility to apoptosis. RESULTS: The lowest ethanol (EtOH) dilution (1:10) of NSEO significantly inhibited the proliferation of CD4+ and CD8+ T cells from HT patients and healthy women by affecting the percentage of dividing cells and the number of cell divisions. In addition, 1:10 and 1:50 NSEO dilutions induced cell death. Different dilutions of NSEO also reduced the concentration of IL-17A and IL-10. In healthy women, the level of IL-4 and IL-2 significantly increased in the presence of 1:10 and 1:50 NSEO dilutions. NSEO did not influence the concentration of IL-6 and IFN-γ. CONCLUSIONS: Our study demonstrates that NSEO has a strong immunomodulatory effect on the lymphocytes of HT patients.

Microfibril Associated Protein 5 (MFAP5) Is Related to Survival of Ovarian Cancer Patients but Not Useful as a Prognostic Biomarker.

Ovarian cancer (OC) is usually diagnosed late due to its nonspecific symptoms and lack of reliable tools for early diagnostics and screening. OC studies concentrate on the search for new biomarkers and therapeutic targets. This study aimed to validate the MFAP5 gene, and its encoded protein, as a potential prognostic biomarker. In our previous study, we found that patients with high-grade serous OC who had higher MFAP5 mRNA levels had shorter survival, as compared with those with lower levels. Here, we used the Kaplan-Meier Plotter and CSIOVDB online tools to analyze possible associations of MFAP5 expression with survival and other clinico-pathological features. In these analyses, higher MFAP5 mRNA expression was observed in the more advanced FIGO stages and high-grade tumors, and was significantly associated with shorter overall and progression-free survival. Next, we analyzed the expression of the MFAP5 protein by immunohistochemistry (IHC) in 108 OC samples and tissue arrays. Stronger MFAP5 expression was associated with stronger desmoplastic reaction and serous vs. non-serous histology. We found no significant correlation between IHC results and survival, although there was a trend toward shorter survival in patients with the highest IHC scores. We searched for co-expressed genes/proteins using cBioPortal and analyzed potential MFAP5 interaction networks with the STRING tool. MFAP5 was shown to interact with many extracellular matrix proteins, and was connected to the Notch signaling pathway. Therefore, although not suitable as a prognostic biomarker for evaluation with a simple diagnostic tool like IHC, MFAP5 is worth further studies as a possible therapeutic target.

Cosmetic Preservatives: Hazardous Micropollutants in Need of Greater Attention?

In recent years, personal care products (PCPs) have surfaced as a novel class of pollutants due to their release into wastewater treatment plants (WWTPs) and receiving environments by sewage effluent and biosolid-augmentation soil, which poses potential risks to non-target organisms. Among PCPs, there are preservatives that are added to cosmetics for protection against microbial spoilage. This paper presents a review of the occurrence in different environmental matrices, toxicological effects, and mechanisms of microbial degradation of four selected preservatives (triclocarban, chloroxylenol, methylisothiazolinone, and benzalkonium chloride). Due to the insufficient removal from WWTPs, cosmetic preservatives have been widely detected in aquatic environments and sewage sludge at concentrations mainly below tens of µg L-1. These compounds are toxic to aquatic organisms, such as fish, algae, daphnids, and rotifers, as well as terrestrial organisms. A summary of the mechanisms of preservative biodegradation by micro-organisms and analysis of emerging intermediates is also provided. Formed metabolites are often characterized by lower toxicity compared to the parent compounds. Further studies are needed for an evaluation of environmental concentrations of preservatives in diverse matrices and toxicity to more species of aquatic and terrestrial organisms, and for an understanding of the mechanisms of microbial degradation. The research should focus on chloroxylenol and methylisothiazolinone because these compounds are the least understood.

In vitro study of the ecotoxicological risk of methylisothiazolinone and chloroxylenol towards soil bacteria.

Methylisothiazolinone (MIT) and chloroxylenol (PCMX) are popular disinfectants often used in personal care products (PCPs). The unregulated discharge of these micropollutants into the environment, as well as the use of sewage sludge as fertilizer and reclaimed water in agriculture, poses a serious threat to ecosystems. However, research into their ecotoxicity towards nontarget organisms is very limited. In the present study, for the first time, the ecotoxicity of biocides to Pseudomonas putida, Pseudomonas moorei, Sphingomonas mali, and Bacillus subtilis was examined. The toxicity of MIT and PCMX was evaluated using the microdilution method, and their influence on the viability of bacterial cells was investigated by the AlamarBlue® test. The ability of the tested bacteria to form biofilms was examined by a microtiter plate assay. Intracellular reactive oxygen species (ROS) production was measured with CM-H2DCFDA. The effect of MIT and PCMX on phytohormone indole-3-acetic acid (IAA) production was determined by spectrophotometry and LC‒MS/MS techniques. The permeability of bacterial cell membranes was studied using the SYTOX Green assay. Changes in the phospholipid profile were analysed using LC‒MS/MS. The minimal inhibitory concentrations (MICs) values ranged from 3.907 to 15.625 mg L-1 for MIT and 62.5 to 250 mg L-1 for PCMX, indicating that MIT was more toxic. With increasing concentrations of MIT and PCMX, the cell viability, biofilm formation ability and phytohormone synthesis were maximally inhibited. Moreover, the growth of bacterial cell membrane permeability and a significantly increased content of ROS were observed, indicating that the exposure caused serious oxidative stress and homeostasis disorders. Additionally, modifications in the phospholipid profile were observed in response to the presence of sublethal concentrations of the chemicals. These results prove that the environmental threat posed by MIT and PCMX must be carefully monitored, especially as their use in PCPs is still growing.

Serum Levels of α-Klotho, Inflammation-Related Cytokines, and Mortality in Hemodialysis Patients.

It has been hypothesized that α-Klotho deficiency might contribute to chronic inflammation in patients with end-stage renal disease (ESRD), especially those on hemodialysis (HD). Serum Klotho levels by some authors are considered a potential predictor of cerebrovascular events. Therefore, we analyzed serum levels of α-Klotho with ELISA and inflammation-related cytokines in HD patients. Sixty-seven HD patients and 19 healthy people were recruited between November 2017 and June 2021. A Cytometric Bead Array (CBA) was used to determine the level of different cytokines: IL-12p70, TNF, IL-10, IL-6, IL-1ß, and IL-8. A human Klotho ELISA kit was used to determine the level of α-Klotho in the plasma samples of HD patients. There was no difference in serum levels of α-Klotho between HD patients and healthy people. Patients had increased serum IL-6 and IL-8. Significant positive correlations existed between the concentration of α-Klotho and the serum concentrations of IL-12p70, IL-10, and IL-1ß. However, in a multivariable linear regression analysis, only patients' age was associated independently with α-Klotho level. Serum α-Klotho was not associated with higher mortality risk in HD patients. While these results draw attention to potential relationships between α-Klotho proteins and inflammatory markers in HD patients, our cross-sectional study could not confirm the pathogenic link between α-Klotho, inflammation, and cardiovascular mortality.

Proteolysis dysfunction in the process of aging and age-related diseases.

In this review, we discuss in detail the most relevant proteolytic systems that together with chaperones contribute to creating the proteostasis network that is kept in dynamic balance to maintain overall functionality of cellular proteomes. Data accumulated over decades demonstrate that the effectiveness of elements of the proteostasis network declines with age. In this scenario, failure to degrade misfolded or faulty proteins increases the risk of protein aggregation, chronic inflammation, and the development of age-related diseases. This is especially important in the context of aging-related modification of functions of the immune system.

The influence of Nigella sativa essential oil on proliferation, activation, and apoptosis of human T lymphocytes in vitro.

In previous work, we tested the immunomodulatory effect of Nigella sativa (NS) fatty oil. Our results demonstrated that unrefined, obtained by cold pressing black cumin seed oil inhibited lymphocytes' proliferation and induced their apoptosis in a dose-dependent manner. In this study, we examined the immunomodulatory properties of essential oil (EO) obtained from the NS seeds by hydrodistillation and its two main constituents: thymoquinone (TQ) and p-cymene. We analyzed the proliferation, activation phenotype, and apoptosis rates of human T lymphocytes stimulated with an immobilized monoclonal anti-CD3 antibody in the presence of serial ethanol dilutions of tested oil or serial distilled water dilutions of tested compounds with flow cytometry. Our results showed that NSEO significantly inhibited the proliferation of CD4+ and CD8+ T lymphocytes, induced cell death in a dose-dependent manner, and reduced the expression of CD28 and CD25 antigens essential for lymphocyte activation. TQ inhibited the proliferation of T lymphocytes and induced cell death, particularly in high concentrations. Meanwhile, p-cymene did not influence lymphocyte proliferation. However, its high concentration induced cell necrosis. These results show that the essential oil from Nigella sativa has powerful immunomodulatory properties, which, at least partially, are related to the TQ component.

The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases.

Autoimmune diseases constitute a heterogeneous group of disorders with one common feature - the loss of immune tolerance towards autoantigens. Due to the complexity of the pathogenesis of these diseases, there are still many open questions regarding their etiology. Therefore, scientists unceasingly search for new data hoping to detect dependable biomarkers and design safe and effective treatment. The research on immune checkpoints is in line with these scientific and clinical demands. Immune checkpoints may be the key to understanding the pathogenesis of many immunological disorders. BTLA-HVEM complex, the inhibitory immune checkpoint, has recently caught scientific attention as an important regulator in different immune contexts, including autoreactivity. So far, the BTLA-HVEM complex has been mainly studied in the context of cancer, but as numerous data show, it may also be a target in the treating of autoimmune diseases. In this review, we intend to focus on the mechanisms of BTLA-HVEM interactions in immune cells and summarize the available data in the context of autoimmunity.