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.

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.

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 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.

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.

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.

Changes in T-Cell Subpopulations and Cytokine Levels in Patients with Treatment-Resistant Depression-A Preliminary Study.

Although there is some evidence for the involvement of cytokines and T cells in the pathophysiology of treatment-resistant depression (TRD), the nature of this relationship is not entirely clear. Therefore, we compared T-cell subpopulations and serum cytokine levels in TRD patients to find relationships between their immunological profiles, clinical presentation, and episode severity. Blood samples from TRD patients (n = 20) and healthy people (n = 13) were collected and analyzed by flow cytometry. We analyzed the percentages of helper and cytotoxic T cells according to the expression of selected activation markers, including CD28, CD69, CD25, CD95, and HLA-DR. The serum levels of inflammatory cytokines IL12p70, TNF-α, IL-10, IL-6, IL-1ß, and IL-8 were also determined. TRD patients had a lower percentage of CD3+CD4+CD25+ and CD3+CD8+CD95+ cells than healthy people. They also had lower serum levels of IL-12p70 and TNF-α, whereas IL-8 levels were significantly higher. Receiver operating characteristic (ROC) analysis demonstrated that serum IL-8 values above 19.55 pg/mL were associated with a 10.26 likelihood ratio of developing TRD. No connections were found between the MADRS score and immunological parameters. These results show that TRD patients have reduced percentages of T cells expressing activation antigens (CD25 and CD95) and higher serum concentrations of proinflammatory and chemotactic IL-8. These changes may indicate reduced activity of the immune system and the important role of IL-8 in maintaining chronic inflammation in the course of depression.

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.

The Synergistic Effect of Triterpenoids and Flavonoids-New Approaches for Treating Bacterial Infections?

Currently, the pharmaceutical industry is well-developed, and a large number of chemotherapeutics are being produced. These include antibacterial substances, which can be used in treating humans and animals suffering from bacterial infections, and as animal growth promoters in the agricultural industry. As a result of the excessive use of antibiotics and emerging resistance amongst bacteria, new antimicrobial drugs are needed. Due to the increasing trend of using natural, ecological, and safe products, there is a special need for novel phytocompounds. The compounds analysed in the present study include two triterpenoids ursolic acid (UA) and oleanolic acid (OA) and the flavonoid dihydromyricetin (DHM). All the compounds displayed antimicrobial activity against Gram-positive (Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Listeria monocytogenes ATCC 19115) and Gram-negative bacteria (Escherichia coli ATCC 25922, Proteus hauseri ATCC 15442, and Campylobacter jejuni ATCC 33560) without adverse effects on eukaryotic cells. Both the triterpenoids showed the best antibacterial potential against the Gram-positive strains. They showed synergistic activity against all the tested microorganisms, and a bactericidal effect with the combination OA with UA against both Staphylococcus strains. In addition, the synergistic action of DHM, UA, and OA was reported for the first time in this study. Our results also showed that combination with triterpenoids enhanced the antimicrobial potential of DHM.

Effect of Quinoline on the Phospholipid Profile of Curvularia lunata and Its Microbial Detoxification.

Quinoline is an N-heterocyclic compound commonly found in wastewater, especially that derived from coal processing, chemical, and pharmaceutical industries. In the present study, the microscopic fungus Curvularia lunata IM 4417, which is known to degrade various xenobiotics, was used. The aim of the research was to study the elimination of quinoline and its influence on fungal phospholipids, which are considered to be excellent indicators of environmental monitoring. Quinoline biodegradation products and phospholipid contents were analyzed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. C. lunata IM 4417 degraded quinoline, which led to the formation of conjugates of glucose with hydroxylated derivatives of the compound. Toxicity tests (Artoxkit M and Microtox assay) indicated that the elimination of lower concentrations of quinoline was efficient and led to a reduction in sample toxicity. The presence of quinoline also significantly affected the profile of fatty acids and phospholipids. The addition of quinoline to a culture of C. lunata IM 4417 caused an increase in the content of phosphatidylcholine (PC) and a decrease in the amount of phosphatidylethanolamine (PE), two major structural lipids. Additionally, decreases in the contents of phosphatidylinositol (PI) and phosphatidylserine (PS), which are responsible for tolerance to toxic substances, cell viability, and signal transduction, were noted. Thus, it can be concluded that the presence of quinoline modifies the membrane composition, and this change may be an important indicator of the presence of N-heterocyclic compounds or other toxins in the environment.

Evaluation of the Antimicrobial Potential and Toxicity of a Newly Synthesised 4-(4-(Benzylamino)butoxy)-9H-carbazole.

One of the greatest threats to human and animal health is posed by infections caused by drug-resistant bacterial strains. Therefore, newly synthesised substances are tested for their antimicrobial activity. Carbazole derivatives seem to be promising antibacterial agents. This study aimed at investigating the toxicity and activity of newly synthesised, functionalised carbazole derivative 2 (4-(4-(benzylamino)butoxy)-9H-carbazole) against various microorganisms. Its antimicrobial potential against Gram-positive and Gram-negative bacteria, yeast, and filamentous fungi was examined according to CLSI (Clinical and Laboratory Standards Institute) standards. The tested compound was found to efficiently inhibit the growth of Gram-positive strains. The addition of carbazole derivative 2 at the concentration of 30 µg/mL caused inhibition of bacterial growth by over 95%. Moreover, about 50 and 45% limitation of Pseudomonas aeruginosa and Aspergillus flavus growth was observed in the samples incubated with the addition of 20 and 60 µg/mL of the compound, respectively. Its addition to the microbial cultures caused an increase in the permeability of the cellular membrane. Slight haemolysis of red blood cells was observed after 24-h treatment with carbazole derivative 2. On the other hand, human fibroblasts were found to be more sensitive to its effects. The activity of the tested compound indicates a possibility of its further modification in order to obtain effective drugs, especially against drug-resistant staphylococci.

Biodegradation of Chloroxylenol by Cunninghamella elegans IM 1785/21GP and Trametes versicolor IM 373: Insight into Ecotoxicity and Metabolic Pathways.

Chloroxylenol (PCMX) is applied as a preservative and disinfectant in personal care products, currently recommended for use to inactivate the SARS-CoV-2 virus. Its intensive application leads to the release of PCMX into the environment, which can have a harmful impact on aquatic and soil biotas. The aim of this study was to assess the mechanism of chloroxylenol biodegradation by the fungal strains Cunninghamella elegans IM 1785/21GP and Trametes versicolor IM 373, and investigate the ecotoxicity of emerging by-products. The residues of PCMX and formed metabolites were analysed using GC-MS. The elimination of PCMX in the cultures of tested microorganisms was above 70%. Five fungal by-products were detected for the first time. Identified intermediates were performed by dechlorination, hydroxylation, and oxidation reactions catalysed by cytochrome P450 enzymes and laccase. A real-time quantitative PCR analysis confirmed an increase in CYP450 genes expression in C. elegans cells. In the case of T. versicolor, spectrophotometric measurement of the oxidation of 2,20-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) showed a significant rise in laccase activity during PCMX elimination. Furthermore, with the use of bioindicators from different ecosystems (Daphtoxkit F and Phytotoxkit), it was revealed that the biodegradation process of PCMX had a detoxifying nature.

Antimicrobial Effect of Chitosan Films on Food Spoilage Bacteria.

Synthetic materials commonly used in the packaging industry generate a considerable amount of waste each year. Chitosan is a promising feedstock for the production of functional biomaterials. From a biological point of view, chitosan is very attractive for food packaging. The purposes of this study were to evaluate the antibacterial activity of a set of chitosan-metal oxide films and different chitosan-modified graphene (oxide) films against two foodborne pathogens: Campylobacter jejuni ATCC 33560 and Listeria monocytogenes 19115. Moreover, we wanted to check whether the incorporation of antimicrobial constituents such as TiO2, ZnO, Fe2O3, Ag, and graphene oxide (GO) into the polymer matrices can improve the antibacterial properties of these nanocomposite films. Finally, this research helps elucidate the interactions of these materials with eukaryotic cells. All chitosan-metal oxide films and chitosan-modified graphene (oxide) films displayed improved antibacterial (C. jejuni ATCC 33560 and L. monocytogenes 19115) properties compared to native chitosan films. The CS-ZnO films had excellent antibacterial activity towards L. monocytogenes (90% growth inhibition). Moreover, graphene-based chitosan films caused high inhibition of both tested strains. Chitosan films with graphene (GO, GOP, GOP-HMDS, rGO, GO-HMDS, rGOP), titanium dioxide (CS-TiO2 20:1a, CS-TiO2 20:1b, CS-TiO2 2:1, CS-TiO2 1:1a, CS-TiO2 1:1b) and zinc oxide (CS-ZnO 20:1a, CS-ZnO 20:1b) may be considered as a safe, non-cytotoxic packaging materials in the future.

Zinc(II) Complexes with Amino Acids for Potential Use in Dermatology: Synthesis, Crystal Structures, and Antibacterial Activity.

The multifunctional profile of Zn2+ has influenced its great popularity in various pharmaceutical, food, and cosmetic products. Despite the use of different inorganic and organic zinc derivatives, the search for new zinc-containing compounds with a safer skin profile still remains an open issue. The present paper describes the synthesis, structural characterization, and antibacterial activity of zinc(II) complexes with proteinogenic amino acids as potential candidates for dermatological treatments. The obtained complexes are of the general formula [Zn(AA)2], where AA represents an amino acid (L-Glu, Gly, L-His, L-Pro, L-Met, and L-Trp). Their synthesis was designed in such a way that the final bis(aminoacidate) zinc(II) complexes did not contain any counter-ions such as Cl-, NO3-, or SO42- that can cause some skin irritations. The chemical structure and composition of the compounds were identified by 1H NMR spectroscopy and elemental analysis, and four were also characterized by single-crystal X-ray diffraction. The Hirshfeld surface analysis for the Zn2+ metallic center helped to determine its coordination number and geometry for each complex. Finally, the antibacterial properties of the complexes were determined with respect to three Gram-positive strains, viz. Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Streptococcus pyogenes ATCC 19615, and two Gram-negative bacteria, viz. Escherichia coli ATCC 25992 and Pseudomonas aeruginosa ATCC 27853, and were compared with the activity of zinc 2-pirrolidone 5-carboxylate (ZnPCA), commonly applied in dermatology. It was found that the Zn(II) complexes with methionine and glycine exhibited a higher antibacterial activity than the tested standard, and the antimicrobial properties of complex with Trp were satisfactory. The results of the antimicrobial activity examination allow us to postulate that the obtained zinc complexes might become new active substances for use in dermatological products.

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target.

BACKGROUND: Immunoglobulin A nephropathy (IgAN), the most frequent cause of primary glomerulonephritis worldwide, is an autoimmune disease with complex pathogenesis. In this review, we focus on T cells and summarize knowledge about their involvement in pathophysiology and treatment of IgAN METHODS: We reviewed the literature for (1) alterations of T cell subpopulations in IgAN, (2) experimental and clinical proofs for T cells' participation in IgAN pathogenesis, (3) clinical correlations with T cell-associated alterations, and (4) influence of drugs used in IgAN therapy on T cell subpopulations. RESULTS: We found that IgAN is characterized by higher proportions of circulatory Th2, Tfh, Th17, Th22 and γδ T cells, but lower Th1 and Treg cells. We discuss genetic and epigenetic makeup that may contribute to this immunological phenotype. We found that Th2, Th17 and Tfh-type interleukins contribute to elevated synthesis of galactose-deficient IgA1 (Gd-IgA1) and that the production of anti-Gd-IgA1 autoantibodies may be stimulated by Tfh cells. We described the roles of Th2, Th17, Th22 and Treg cells in the renal injury and summarized correlations between T cell-associated alterations and clinical features of IgAN (proteinuria, reduced GFR, hematuria). We detailed the impact of immunosuppressive drugs on T cell subpopulations and found that the majority of drugs have nonoptimal influence on T cells in IgAN patients. CONCLUSIONS: T cells play an important role in IgAN pathogenesis and are correlated with its clinical severity. Clinical trials with the drugs targeting the reported alterations of the T-cell compartment are highly desirable.

Associated Effects of Cadmium and Copper Alter the Heavy Metals Uptake by Melissa Officinalis.

Lemon balm (Melissa officinalis) is a popular herb widely used in medicine. It is often cultivated in soils with substantial heavy metal content. Here we investigate the associated effects of cadmium and copper on the plant growth parameters augmented by the manganese, zinc, and lead uptake indicators. The concentration of all elements in soil and plants was determined by the HR-CS FAAS with the ContrAA 300 Analytik Jena spectrometer. Bioavailable and total forms calculated for all examined metals were augmented by the soil analyses. The index of chlorophyll content in leaves, the activity of net photosynthesis, stomatal conductance, transpiration rate, and intercellular concentration of CO2 were also investigated. Either Cd or Cu acting alone at high concentrations in soil are toxic to plants as indicated by chlorophyll indices and gas exchange parameters. Surprisingly, this effect was not observed when both metals were administered together. The sole cadmium or copper supplementations hampered the plant's growth, lowered the leaf area, and altered the plant's stem elongation. Analysis of variance showed that cadmium and copper treatments of lemon balm significantly influenced manganese, lead, and zinc concentration in roots and above ground parts.

The Synergy of Ciprofloxacin and Carvedilol against Staphylococcus aureus-Prospects of a New Treatment Strategy?

Staphylococcus aureus infections are common and difficult to treat. The increasing number of drug-resistant staphylococcal infections has created the need to develop new strategies for the treatment of these infections. The synergistic antimicrobial activity of different pharmaceuticals seems to be an interesting alternative. The aim of this study was to assess the synergistic activity of ciprofloxacin and carvedilol against S. aureus strains. The antibacterial potential of ciprofloxacin and carvedilol was evaluated according to the CLSI guidelines. The calcium content in S. aureus cells was measured using flow cytometry and atomic absorption spectroscopy. Moreover, confocal and scanning electron microscopy were used to determine the mechanism of antibacterial synergy of ciprofloxacin and carvedilol. The antibacterial effect of ciprofloxacin was higher in the presence of carvedilol than in S. aureus cultures containing the antibiotic only. A significant increase in S. aureus membrane permeability was also observed. The simultaneous administration of the tested compounds caused damage to S. aureus cells visualized by SEM. Enhancement of the antimicrobial action of ciprofloxacin by carvedilol was correlated with an increase in free calcium content in S. aureus cells, morphological changes to the cells, and a reduction in the ability to form bacterial aggregates.

Synergistic Effects of Anionic/Cationic Dendrimers and Levofloxacin on Antibacterial Activities.

Despite the numerous studies on dendrimers for biomedical applications, the antibacterial activity of anionic phosphorus dendrimers has not been explored. In our research, we evaluated the antibacterial activity of modified polycationic and polyanionic dendrimers in combination with levofloxacin (LVFX) against Gram-negative (Escherichia coli ATCC 25922, Proteus hauseri ATCC 15442) and Gram-positive (Staphylococcus aureus ATCC 6538) bacteria. In the case of Gram-negative bacteria, we concluded that a combination of dendrimers and antibiotic gave satisfactory results due to a synergistic effect. The use of fluoroquinolone antibiotics, such as LVFX, not only caused resistance in disease-causing microorganisms but also increased environmental pollution. Therefore, reduction of drug dosage is of general interest.

The immunomodulatory effect of ketamine in depression.

Major depression is one of the most frequent psychiatric conditions. Despite many available treatment methods, more than 30% of patients do not achieve remission, even after trying several antidepressants and augmentation strategies. S-enantiomer of ketamine, well-known anesthetic and analgesic, has been recently approved by Food and Drug Administration in the intranasal form as a new generation antidepressant. However, the mechanism in which ketamine reduces depressive symptoms in treatment-resistant depression patients is still not completely understood. There are several theories explaining how ketamine might reduce depressive symptoms, which have been described in detail; one of them is immunomodulatory effect of ketamine, according to the inflammatory theory of depression. In the review authors present and summarize studies showing ketamine effect on human immune system ex vivo and in vitro, including changes in cytokine levels, number, ratio and activity of various immune cell population and the correlation with clinical improvement in depressive symptoms. Most of the results confirm the anti-inflammatory effect of ketamine. There are only a few studies in the population of patients suffering from depression receiving ketamine, focused on correlation between immunological changes and clinical outcome of the therapy; further studies of that area are neccesary for understanding the immunomodulatory effect of ketamine in depression.

Establishment and Characterization of the Novel High-Grade Serous Ovarian Cancer Cell Line OVPA8.

High-grade serous ovarian carcinoma (HGSOC) is the most frequent histological type of ovarian cancer and the one with worst prognosis. Unfortunately, the majority of established ovarian cancer cell lines which are used in the research have unclear histological origin and probably do not represent HGSOC. Thus, new and reliable models of HGSOC are needed. Ascitic fluid from a patient with recurrent HGSOC was used to establish a stable cancer cell line. Cells were characterized by cytogenetic karyotyping and short tandem repeat (STR) profiling. New generation sequencing was applied to test for hot-spot mutations in 50 cancer-associated genes and fluorescence in situ hybridization (FISH) analysis was used to check for TP53 status. Cells were analyzed for expression of several marker genes/proteins by reverse-transcription polymerase chain reaction (RT-PCR), fluorescence-activated cell sorting (FACS), and immunocytochemistry (ICC). Functional tests were performed to compare OVPA8 cells with five commercially available and frequently used ovarian cancer cell lines: SKOV3, A2780, OVCAR3, ES2, and OAW42. Our newly-established OVPA8 cell line shows morphologic and genetic features consistent with HGSOC, such as epithelial morphology, multiple chromosomal aberrations, TP53 mutation, BRCA1 mutation, and loss of one copy of BRCA2. The OVPA8 line has a stable STR profile. Cells are positive for EpCAM, CK19, and CD44; they have relatively low plating efficiency/ability to form spheroids, a low migration rate, and intermediate invasiveness in matrigel, as compared to other ovarian cancer lines. OVPA8 is sensitive to paclitaxel and resistant to cisplatin. We also tested two FGFR inhibitors; OVPA8 cells were resistant to AZD4547 (AstraZeneca, London, UK), but sensitive to the new inhibitor CPL304-110-01 (Celon Pharma, Lomianki/Kielpin, Poland). We have established and characterized a novel cell line, OVPA8, which can be a valuable preclinical model for studies on high-grade serous ovarian cancer.