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The objective of this study was to present a comparative analysis of the antimicrobial activity of methanolic leaf extracts from seven Juniperus L. species, together with a tentative analysis of their total flavonoid and o-dihydroxyphenolic acids content. The chemical analyses were performed by colorimetric methods and the antimicrobial activity was assessed via broth microdilution. The studied extracts showed total content of o-dihydroxyphenols in the range of 26 to 34 µg of caffeic acid equivalent/mg DE and total flavonoid content of 13 to 24 µg of quercetin equivalent/mg DE. The sensitivity of Gram-positive bacteria to the studied extracts differed significantly with the following order of activity: J. sabina var. balkanensis > J. communis ‘Laxa’ > J. formosana > J. pinchotii > J. ashei > J. excelsa ≈ J. sibirica. Weak activity was observed for all extracts against Gram-negative bacteria and Candida strains. The analysis of the MBC/MIC ratio showed that the extracts exhibited bactericidal effect against Gram-negative bacteria (MBC/MIC≤4), while bactericidal or bacteriostatic action (MBC/MIC>4) was determined towards Gram-positive bacteria. Moreover, these extracts showed fungicidal (MFC/MIC≤4) or fungistatic effect (MFC/MIC>4). Best antibacterial activity was registered for the J. sabina var. balkanensis leaf extract. The multivariate data analyses were carried out by SIMCA 16 (v16.0.2) software. The hierarchical cluster analysis and principal component analysis, based on phytochemical and antimicrobial data, classified the studied juniper species into four groups: 1. J. ashei; 2. J. excelsa, J. sibirica; 3. J. sabina var. balkanensis, J. communis Laxa, J. formosana; 4. J. pinchotii.

Streptococcus pneumoniae is one of the most frequent bacterial identified causes of community-acquired pneumonia, otitis media and meningitis. It is, as well, a common cause of bacteraemia’s significant morbidity and mortality. Beta-lactam antibiotics (BLAs) are the first line of empirical treatment for pneumococcal infections. The targets of BLAs are penicillin-binding proteins (PBPs), the modifications of which are one of the reasons why pneumococci are non-susceptible to BLAs. In our work, a total of 39 Streptococcus pneumoniae isolates were obtained from 176 healthy children, both vaccinated and non-vaccinated. The isolates were tested for antimicrobial susceptibility, and their penicillin-binding proteins (PBPs) were typed by the restriction fragment length of the polymorphism analysis of their pbp genes. The most frequent serotypes among the penicillin non-susceptible Streptococcus pneumoniae (PNSSP) isolates were 23B, 35B and 19F. Restriction enzyme analyses of pbp1a, pbp2b, and pbp2x genes revealed 5, 3 and 3 different patterns, respectively, and a total of 4 different PBPs profiles of PNSSP isolates belonging to serotypes not included in pneumococcal conjugate vaccines were demonstrated. We conclude that the level of resistance should be monitored constantly to ascertain the effect of current pneumococcal conjugate vaccines, as well as to recognize new circumstances developing in Poland, as well as the possibility of multiple, independent imports of resistant strains from abroad.

The aim of this study was to analyze the quality of 10 commonly available commercial probiotic products used in Poland. These items were tested for the total viable bacterial count, and for identifying the isolated strains. This was performed using the Polymerase Chain Reaction method. The results showed that five of the tested products had not the applicable number of viable bacteria declared by manufacturer. Moreover, not all declared probiotic strains were found in three of the tested products during analyses. It is clear that a regular control of probiotic products needs be introduced that can guarantee its beneficial properties.

Hyssopus officinalis L. is a common plant that is most usually found in three color forms - f. cyaneus (blue), f. ruber Mill. (purple/pink) and f. albus Alef (white). In the present work, we evaluated the chemical composition and antimicrobial activity of essential oils obtained from Polish-sourced white- and pink-flowered H. officinalis. Gas chromatography-mass spectrometry analysis of the essential oil has shown that both forms of color have a different content of main components. The principle essential oil component of white-flowered H. officinalis L. was pinocamphone (51%), while pink-flowered H. officinalis L. contained almost equal amounts of pinocamphone (28.8%) and isopinocamphone (21.9%). Of note, the essential oil of the pink form was more active against Grampositive bacteria, especially against Bacillus subtilis.

Recently, several studies have been undertaken so as to develop more effective therapeutic approaches towards eradicating Helicobacter pylori. Among these is phytotherapy. The aim of this study was to investigate the activity in vitro of the plant extracts obtained from common herbs cultivated in the Lubelszczyzna region against the reference strain H. pylori ATCC 43504. Among these are thyme herbs, chamomile flowers, peppermint leaves and coneflower herbs. Herein, it was found that the MIC values of the assayed extracts were as follows: the extracts from coneflower herbs showed anti-H. pylori activity with MIC = 31.3-125 μg/ml; the extracts from chamomile flowers demonstrated MIC = 31.3-62.5 μg/ ml; the extracts from peppermint leaves had MIC = 15.6-250 μg/ml; and the extracts from thyme herbs revealed MIC = 15.6-62.5 μg/ml, depending on the solvent used. The most active were the extracts obtained with ethyl acetate or ethanol alcohol absolute 99.8%. These showing MIC within the range of 15.6-62.5 μg/ml, while the lowest activity was observed in case of the extract obtained with 70% aqueous ethanol. This last showing MIC within the range of 62.5-250 μg/ml. The MIC values of essential oil components were 15.6 μg/ml for bisabolol and menthol or 31.3 μg/ml for thymol. The obtained data indicate that the assayed herbs possessed promising anti-H. pylori bioactivity.

Two compounds, benzyl-2-(amino(pyrazin-2-yl)methylene)-1-methylhydrazine-1-carbodithioate (L) and its copper(ii) complex Cu(L) were synthesized and studied in terms of their physicochemical properties, including single crystal, spectroscopic and magnetic properties; in silico simulations, including DFT calculations and pharmacokinetic profile analysis; and in vitro biological activity. The Cu(L) compound was found to exhibit good anticancer activity against A375, PANC-1, MKN-74, T-47D, HeLa, and NCI-H1563 cells, with the IC 50 value against the HeLa cell line reaching 17.50 μM, significantly surpassing the activity of the organic ligand. Moreover, at the same time, the Cu(L) complex did not exhibit significant toxicity towards healthy cells. Mechanism of action studies revealed that its activity is connected with the oxidative stress and redox imbalance caused by the upregulation of genes encoding superoxide dismutase (SOD2) and catalase (CAT) antioxidant enzymes. The reported results further underscore the anticancer potential of pyrazine-based copper(ii) complexes., Competing Interests: The Authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Introduction: Epstein-Barr virus (EBV) reactivation is increasingly recognized as a potential exacerbator of autoimmune diseases, including Hashimoto's thyroiditis (HT)., Objectives: This study examined the association between EBV reactivation and intracellular Toll-like receptors (TLRs) expression in newly diagnosed, untreated HT patients. The aim was to determine whether EBV reactivation and specific TLRs (TLR3, TLR7, TLR8, and TLR9) contribute to the pathogenesis and progression of HT., Patients and Methods: A cohort was 54 newly diagnosed, untreated patients with HT and 20 healthy volunteers (HV). Also, the HV were similar in age and gender. Blood samples were collected to assess EBV viral load and intracellular expression levels of TLR3, TLR7, TLR8, and TLR9 using flow cytometry. Specific anti-EBV antibodies (e.g., VCA IgM, VCA IgG, EBNA-1 IgM, EBNA-1 IgG) were measured to identify signs of EBV reactivation, while soluble TLRs (sTLR3, sTLR7, sTLR8, and sTLR9) were quantified in serum using ELISA. Notably, this study's patients with Hashimoto's thyroiditis were not euthyroid, as they exhibited significantly lower TSH levels and elevated fT3 and fT4 levels compared to healthy controls., Results: Results showed a significant increase in EBV reactivation among HT patients, with 26 of 54 (48.1%) testing positive for EBV DNA, compared to none in the control group. HT patients with reactivated EBV showed significantly higher levels of intracellular expression of TLR3, TLR7, and TLR9, with TLR3+ cells constituting an average of 4.72% of CD4+ lymphocytes compared to 0.69% in the control group, suggesting a potential synergistic effect. In addition, soluble TLR levels were increased in HT patients with reactivated EBV, suggesting a potential role in potentiating autoimmune responses., Conclusions: These findings highlight the importance of considering both viral reactivation and TLR activity in the treatment of HT. Understanding the interplay between EBV and intracellular TLRs may lead to the development of new therapeutic approaches to mitigate the impact of these factors on disease progression. Further research is warranted to investigate the mechanisms underlying this interaction and its implications for treatment strategies.

The role of programmed death cell protein 1 (PD-1) has already been described in a range of various diseases, including COVID-19. This study provides new, innovative data, related to the expression of PD-1 and the risk of Paediatric Inflammatory Multisystem Syndrome, temporally associated with SARS-CoV-2 infection (PIMS-TS)-a rare, but potentially life-threatening complication of COVID-19. In this study, we evaluated the expression of PD-1 protein in patients with PIMS. Blood samples were taken from patients at the time of diagnosis (n = 33), after 6 weeks (n = 33), 3 months (n = 24), 6 months (n = 24) and 12 months (n = 8). The immunophenotypes were evaluated in flow cytometry. The control group consisted of 35 healthy children with negative SARS-CoV-2 antigen/PCR test, who were asymptomatic and had no history of allergic, autoimmune or oncological diseases. The associations between immunophenotypes, biochemical findings and clinical data were analysed. Significant increases in the expression of PD-1 for CD4+ and CD8+ T cells, compared to the control group, were observed in the day of admission, with a gradual decrease during the first weeks from initiation of treatment. This study sheds new light on the pathogenesis of PIMS-TS, emphasizing the role of PD-1 protein. Future research is essential for early risk prediction in SARS-CoV-2 patients and for devising effective clinical prevention and management strategies.

Hemp ( Cannabis sativa L.) has been used for millennia as a rich source of food and fibers, whereas hemp flowers have only recently gained an increased market interest due to the presence of cannabinoids and volatile terpenes. Currently, the hemp flower processing industry predominantly focuses on either cannabinoid or terpene extraction. In an attempt to maximize the valorization of hemp flowers, the current study aimed to evaluate the phytochemical composition and antimicrobial properties of several extracts obtained from post-distillation by-products (e.g., spent material, residual distillation water) in comparison to the essential oil and total extract obtained from unprocessed hemp flowers. A terpene analysis of the essential oil revealed 14 monoterpenes and 35 sesquiterpenes. The cannabinoid profiling of extracts showed seven acidic precursors and 14 neutral derivatives, with cannabidiol (CBD) reaching the highest concentration (up to 16 wt.%) in the spent material extract. The antimicrobial assessment of hemp EO, cannabinoid-containing extracts, and single compounds (i.e., CBD, cannabigerol, cannabinol, and cannabichromene) against a panel of 20 microbial strains demonstrated significant inhibitory activities against Gram-positive bacteria, Helicobacter pylori , and Trichophyton species. In conclusion, this work suggests promising opportunities to use cannabinoid-rich materials from hemp flower processing in functional foods, cosmetics, and pharmaceuticals with antimicrobial properties.

(1) Background: Non-small-cell lung cancer (NSCLC) represents a significant global health challenge, contributing to numerous cancer deaths. Despite advances in diagnostics and therapy, identifying reliable biomarkers for prognosis and therapeutic stratification remains difficult. Toll-like receptors (TLRs), crucial for innate immunity, now show potential as contributors to cancer development and progression. This study aims to investigate the role of TLR expression as potential biomarkers in the development and progression of NSCLC. (2) Materials and Methods: The study was conducted on 89 patients diagnosed with NSCLC and 40 healthy volunteers, for whom the prevalence of TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was assessed on selected subpopulations of T and B lymphocytes in the peripheral blood of recruited patients along with the assessment of their serum concentration. (3) Result: Our study showed several significant changes in NSCLC patients at the beginning of the study. This resulted in a 5-year follow-up of changes in selected TLRs in recruited patients. Due to the high mortality rate of NSCLC patients, only 16 patients survived the 5 years. (4) Conclusions: The results suggest that TLRs may constitute real biomarker molecules that may be used for future prognostic purposes in NSCLC. However, further validation through prospective clinical and functional studies is necessary to confirm their clinical utility. These conclusions may lead to better risk stratification and tailored interventions, benefiting NSCLC patients and bringing medicine closer to precision.

Four alkaline earth metal complexes of ketoprofen (Hket) and indomethacin (Hind) were synthesized and characterized: [Ca(ket) 2 (H 2 O) 2 ] n (1), [Mg(ket) 2 (H 2 O) 2 ] (2), [Ca(ind) 2 (EtOH) 2 ] n (3), and [Mg(ind) 2 (EtOH) 2 ] (4). All compounds were studied by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Crystal structures of 1 and 3 were determined by single crystal X-ray diffraction technique T=100 K. The structure of 1 is dominated by a one-dimensional coordination polymer, while 3 is formed by a two-dimensional layer stabilized by the calcium zig-zag chains and π⋅⋅⋅π stacking interactions. Crystal packing arrangements were characterized by fingerprint plots (FPs) that were derived from the Hirshfeld surfaces (HSs). The antioxidant and antimicrobial activities of complexes were evaluated against Gram-positive and Gram-negative bacteria as well as yeasts., (© 2024 Wiley-VCH GmbH.)

This research's scope encompassed biotechnological, phytochemical, and biological studies of Schisandra henryi , including investigations into its in vitro microshoot culture grown in PlantForm bioreactors (temporary immersion systems, TISs), as well as extracts from leaves of the parent plant, focusing on anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. The phytochemical analysis included the isolation and quantification of 17 compounds from dibenzocyclooctadiene, aryltetralin lignans, and neolignans using centrifugal partition chromatography (CPC), HPLC-DAD, and UHPLC-MS/MS tandem mass spectrometry with triple quadrupole mass filter methods. Higher contents of compounds were found in microshoots extracts (max. 543.99 mg/100 g DW). The major compound was schisantherin B both in the extracts from microshoots and the leaves (390.16 and 361.24 mg/100 g DW, respectively). The results of the anti-inflammatory activity in terms of the inhibition of COX-1, COX-2, sPLA2, and LOX-15 enzymes indicated that PlantForm microshoot extracts showed strong activity against COX-1 and COX-2 (for 177 mg/mL the inhibition percentage was 76% and 66%, respectively). The antioxidant potential assessed using FRAP, CUPRAC, and DPPH assays showed that extracts from microshoot cultures had 5.6, 3.8, and 3.3 times higher power compared to extracts from the leaves of the parent plant, respectively. The total polyphenol content (TPC) was 4.1 times higher in extracts from the in vitro culture compared to the leaves. The antiproliferative activity against T-cell lymphoblast line Jurkat, breast adenocarcinoma cultures (MCF-7), colon adenocarcinoma (HT-29), and cervical adenocarcinoma (HeLa), showed that both extracts have considerable effects on the tested cell lines. The antimicrobial activity tested against strains of Gram-positive and Gram-negative bacteria and fungi showed the highest activity towards H. pylori (MIC and MBC 0.625 mg/mL).

Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays. Results: The results of the study showed that NSCLC patients responded to the vaccine with an increase in the frequencies of plasmablasts and antibodies but to a lesser extent than healthy controls. The immune system response to PCV13 vaccination was better in patients with lower-stage NSCLC. We found higher antibody levels after vaccination in NSCLC patients who survived 5 years of follow-up. Conclusions: We hope that our research will contribute to increasing patients' and physicians' awareness of the importance of including PCV13 vaccinations in the standard of oncological care, which will extend the survival time of patients and improve their quality of life.

Iron oxide nanoparticles (IONPs) have many practical applications, ranging from environmental protection to biomedicine. IONPs are being investigated due to their high potential for antimicrobial activity and lack of toxicity to humans. However, the biological activity of IONPs is not uniform and depends on the synthesis conditions, which affect the shape, size and surface modification. The aim of this work is to synthesise IONPs using a mixed method, i.e., chemical co-precipitation combined with biogenic surface modification, using extracts from spent hops ( Humulus lupulus L.) obtained as waste product from supercritical carbon dioxide hop extraction. Different extracts (water, dimethyl sulfoxide (DMSO), 80% ethanol, acetone, water) were further evaluated for antioxidant activity based on the silver nanoparticle antioxidant capacity (SNPAC), total phenolic content (TPC) and total flavonoid content (TFC). The IONPs were characterised via UV-vis spectroscopy, scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS) and Fourier-transform infrared (FT-IR) spectroscopy. Spent hop extracts showed a high number of flavonoid compounds. The efficiency of the solvents used for the extraction can be classified as follows: DMSO > 80% ethanol > acetone > water. FT-IR/ATR spectra revealed the involvement of flavonoids such as xanthohumol and/or isoxanthohumol, bitter acids (i.e., humulones, lupulones) and proteins in the surface modification of the IONPs. SEM images showed a granular, spherical structure of the IONPs with diameters ranging from 81.16 to 142.5 nm. Surface modification with extracts generally weakened the activity of the IONPs against the tested Gram-positive and Gram-negative bacteria and yeasts by half. Only the modification of IONPs with DMSO extract improved their antibacterial properties against Gram-positive bacteria ( Staphylococcus epidermidis , Staphylococcus aureus , Micrococcus luteus , Enterococcus faecalis , Bacillus cereus ) from a MIC value of 2.5-10 mg/mL to 0.313-1.25 mg/mL.

Buds of poplar trees ( Populus species) are often covered with sticky, usually polyphenol-rich, exudates. Moreover, accessible data showed that some Populus bud extracts may be excellent antibacterial agents, especially against Gram-positive bacteria. Due to the fragmentary nature of the data found, we conducted a systematic screening study. The antimicrobial activity of two extract types (semi-polar-ethanolic and polar-ethanolic-water (50/50; V / V )) from 27 bud samples of different poplar taxons were compared. Antimicrobial assays were performed against Gram-positive (five strains) and Gram-negative (six strains) bacteria as well as fungi (three strains) and covered the determination of minimal inhibitory, bactericidal, and fungicidal concentrations. The composition of extracts was later investigated by ultra-high-performance liquid chromatography coupled with ultraviolet detection (UHPLC-DAD) and with electrospray-quadrupole-time-of-flight tandem mass spectrometry (UHPLC-ESI-qTOF-MS). As a result, most of the extracts exhibited good (MIC ≤ 62.5 µg/mL) or moderate (62.5 < MIC ≤ 500 µg/mL) activity against Gram-positives and Helicobacter pylori , as well as fungi. The most active were ethanolic extracts from P . trichocarpa , P . trichocarpa clone 'Robusta', and P . tacamahaca × P . trichocarpa . The strongest activity was observed for P . tacamahaca × P . trichocarpa . Antibacterial activity was supposedly connected with the abundant presence of flavonoids (pinobanksin, pinobanksin 3-acetate, chrysin, pinocembrin, galangin, isosakuranetin dihydrochalcone, pinocembrin dihydrochalcone, and 2',6'-dihydroxy-4'-methoxydihydrochalcone), hydroxycinnamic acids monoesters ( p -methoxycinnamic acid cinnamyl ester, caffeic acid phenethylate and different isomers of prenyl esters), and some minor components (balsacones).

Four copper(II) complexes, C1 - 4 , derived from 1-(isoquinolin-3-yl)heteroalkyl-2-one ligands L1 - 4 were synthesized and characterized using an elemental analysis, IR spectroscopic data as well as single crystal X-ray diffraction data for complex C1 . The stability of complexes C1 - 4 under conditions mimicking the physiological environment was estimated using UV-Vis spectrophotometry. The antiproliferative activity of both ligands L1 - 4 and copper(II) compounds C1 - 4 were evaluated using an MTT assay on four human cancer cell lines, A375 (melanoma), HepG2 (hepatoma), LS-180 (colon cancer) and T98G (glioblastoma), and a non-cancerous cell line, CCD-1059Sk (human normal skin fibroblasts). Complexes C1 - 4 showed greater potency against HepG2, LS180 and T98G cancer cell lines than etoposide (IC 50 = 5.04-14.89 μg/mL vs. IC 50 = 43.21->100 μg/mL), while free ligands L1 - 4 remained inactive in all cell lines. The prominent copper(II) compound C2 appeared to be more selective towards cancer cells compared with normal cells than compounds C1 , C3 and C4 . The treatment of HepG2 and T98G cells with complex C2 resulted in sub-G1 and G2/M cell cycle arrest, respectively, which was accompanied by DNA degradation. Moreover, the non-cytotoxic doses of C2 synergistically enhanced the cytotoxic effects of chemotherapeutic drugs, including etoposide , 5-fluorouracil and temozolomide , in HepG2 and T98G cells. The antimicrobial activities of ligands L2 - 4 and their copper(II) complexes C2 - 4 were evaluated using different types of Gram-positive bacteria, Gram-negative bacteria and yeast species. No correlation was found between the results of the antiproliferative and antimicrobial experiments. The antioxidant activities of all compounds were determined using the DPPH and ABTS radical scavenging methods. Antiradical tests revealed that among the investigated compounds, copper(II) complex C4 possessed the strongest antioxidant properties. Finally, the ADME technique was used to determine the physicochemical and drug-likeness properties of the obtained complexes.

Two new 2-(pyridin-2-yl)-1H-benzimidazole derivatives, namely, 2-(4-phenoxypyridin-2-yl)-1H-benzimidazole, C 18 H 13 N 3 O, and 2-[4-(4-fluorophenoxy)pyridin-2-yl]-1H-benzimidazole, C 18 H 12 FN 3 O, were synthesized and characterized by NMR spectroscopy. Crystal structure, biological activity and ADME analyses were performed for these two new compounds and a third compound, namely, 5,6-dimethyl-2-[4-(4-phenylpiperazin-1-yl)pyridin-2-yl]-1H-benzimidazole methanol monosolvate, C 24 H 25 N 5 ·CH 3 OH, the synthesis of which had been described previously. All three compounds have a similar chain hydrogen-bonding pattern. One of them (the fluorophenoxy derivative) showed good antimicrobial activity against Gram-positive bacteria. The ADME analysis indicates that the compounds could be good drug candidates.

Introduction: A healthy vaginal microbiota is represented mainly by Lactobacillus spp. and plays a vital role in maintaining the functional balance in the vaginal environment. Scientists have drawn attention to possible correlations between the vaginal microbiome and gynecological neoplasms. Several recent studies have shown a potential link between the vaginal microbiome and the risk of developing cervical cancer from human papillomavirus (HPV) infection. This study aimed to compare the prevalence and abundance of various lactic acid bacteria species (LABs) in vaginal swabs from healthy controls and patients with abnormal Pap smear results., Methods: The study included 100 women (79 patients with abnormal cervical Pap smear results and 21 controls) from whom vaginal swabs were collected. Real-time quantitative PCR was used to determine seven lactic acid bacteria (LAB) species and their quantities., Results: Most patients were colonized by two Lactobacillus species, primarily Lactobacillus gasseri (93%) and L. crispatus (83%). Patient age and place of residence were associated with the diversity of LAB in the vaginal microbiota. The abundance of L. delbrueckii in the vaginal microbiota increased, whereas the abundance of L. gasseri abundance decreased, with patient age. Lactobacillus acidophilus and Limosilactobacillus fermentum were significantly more often detected in patients living in rural versus urban areas. Statistical analysis did not show any significant differences in LAB between groups of patients with various changes on smear tests., Discussion: The degree of dysplastic changes in the endothelium or the presence of a group of atypical cervical stratified epithelial cells was not associated with significant changes in the studied vaginal bacteria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Frąszczak, Barczyński, Siwiec, Kondracka, Malm, Kotarski, Witt and Korona-Głowniak.)

To investigate how structural modifications affect tuberculostatic potency, we synthesized seven new piperidinothiosemicrabazone derivatives 8 - 14 , in which three of them had a pyrazine ring replacing the pyridine ring. Derivatives 8 - 9 and 13 - 14 exhibited significant activity against the standard strain (minimum inhibitory concentration (MIC) 2-4 μg/mL) and even greater activity against the resistant M. tuberculosis strain (MIC 0.5-4 μg/mL). Additionally, the effects of compounds 8 - 9 were entirely selective (MIC toward other microorganisms ≥ 1000 μg/mL) and non-toxic (IC50 to HaCaT cells 5.8 to >50 μg/mL). The antimycobacterial activity of pyrazine derivatives 11 - 12 was negligible (MIC 256 to >500 μg/mL), indicating that replacing the aromatic ring was generally not a promising line of research in this case. The zwitterionic structure of compound 11 was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion (ADME) calculations showed that all compounds, except 11 , could be considered for testing as future drugs. An analysis of the structure-activity relationship was carried out, indicating that the higher basicity of the substituent located at the heteroaromatic ring might be of particular importance for the antituberculous activity of the tested groups of compounds.

Helicobacter pylori infections are highly common amongst the global population. Such infections have been shown to be the cause of gastric ulcers and stomach carcinoma and, unfortunately, most cases are asymptomatic. Standard treatment requires antibiotics such as metronidazole or azithromycin to which many strains are now resistant. Mentha species have been used as a natural treatment for gastrointestinal diseases throughout history and essential oils (EOs) derived from these plants show promising results as potential antimicrobial agents. In this study, EOs obtained from the leaves and flowers of five cultivars of Mentha × piperita and M. spicata were examined by GC-MS. The investigated mints are representatives of four chemotypes: the menthol chemotype ( M. × piperita 'Multimentha' and M. × piperita 'Swiss'), the piperitenone oxide chemotype ( M. × piperita 'Almira'), the linalool chemotype ( M. × piperita 'Granada'), and the carvone chemotype ( M. spicata 'Moroccan'). The chemical composition of EOs from mint flowers and leaves was comparable with the exception of the Swiss cultivar. Menthol was the most abundant component in the leaves while menthone was highest in flowers. The H. pylori ATCC 43504 reference strain and 10 other H. pylori clinical strains were examined for their sensitivity to the EOs in addition to their major monoterpenoid components (menthol, menthone, carvone, dihydrocarvone, linalool, 1,8-cineole, and limonene). All tested mint EOs showed inhibitory activity against both the reference H. pylori ATCC 43504 strain (MIC 15.6-31.3 mg/L) and clinical H. pylori strains (MIC 50/90 31.3-250 mg/L/62.5-500 mg/L). Among the reference monoterpenes, menthol (MIC 50/90 7.8/31.3 mg/L) and carvone (MIC 50/90 31.3/62.5 mg/L) had the highest anti- H. pylori activity, which also correlated with a higher activity of EOs containing these compounds ( M. × piperita 'Swiss' and M. spicata 'Moroccan'). A synergistic and additive interaction between the most active EOs/compounds and antibiotics possibly points to a new plant-based anti- H. pylori treatment.

Phytogenically synthesised nanoparticle (NP)-based drug delivery systems have promising potential in the field of biopharmaceuticals. From the point of view of biomedical applications, such systems offer the small size, high surface area, and possible synergistic effects of NPs with embedded biomolecules. This article describes the synthesis of silver nanoparticles (Ag-NPs) using extracts from the flowers and leaves of tansy ( Tanacetum vulgare L.), which is known as a remedy for many health problems, including cancer. The reducing power of the extracts was confirmed by total phenolic and flavonoid content and antioxidant tests. The Ag-NPs were characterised by various analytical techniques including UV-vis spectroscopy, scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS), Fourier transform infrared (FT-IR) spectroscopy, and a dynamic light scattering (DLS) system. The obtained Ag-NPs showed higher cytotoxic activity than the initial extracts against both human cervical cancer cell lines HeLa (ATCC CCL-2) and human melanoma cell lines A375 and SK-MEL-3 by MTT assay. However, the high toxicity to Vero cell culture (ATCC CCL-81) and human fibroblast cell line WS-1 rules out the possibility of their use as anticancer agents. The plant-mediated Ag-NPs were mostly bactericidal against tested strains with MBC/MIC index ≤4. Antifungal bioactivity ( C. albicans, C. glabrata, and C. parapsilosis ) was not observed for aqueous extracts (MIC > 8000 mg L -1 ), but Ag-NPs synthesised using both the flowers and leaves of tansy were very potent against Candida spp., with MIC 15.6 and 7.8 µg mL -1 , respectively.

Three new 2,6-disubstituted thiosemicarbazone derivatives of pyridine, namely, 2-{amino[6-(pyrrolidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C 13 H 20 N 6 S, 2-{amino[6-(piperidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C 14 H 22 N 6 S, and 2-[amino(6-phenoxypyridin-2-yl)methylidene]-N,N-dimethylhydrazine-1-carbothioamide monohydrate, C 15 H 17 N 5 OS·H 2 O, have been synthesized and characterized by NMR spectroscopy and low-temperature single-crystal X-ray diffraction. In addition, their antibacterial and anti-yeast activities have been determined. The ability of the tested compounds to inhibit bacterial growth was comparable to vancomycin as a reference drug. Compared to isoniazid (MIC 0.125 and 8 µg ml -1 ), the compounds showed the ability to inhibit the growth of Mycobacterium tuberculosis to a moderate degree for the standard strain and at the same level or higher (MIC 4-8 µg ml -1 ) for the resistant strain. All three compounds adopt the zwitterionic form in the crystal structure regardless of the presence or absence of solvent molecules.

Lagovirus europaeus/GI.1 is the virus that causes severe and dangerous rabbit haemorrhagic disease (RHD) in rabbits. Recombination formation in RHD viruses is common. Recombination is thought to play a key role in the evolution of lagoviruses and therefore most likely influences the pathogenicity of L. europaeus/GI strains. Immunological events also play a key role in the control of RHD, and an in-depth knowledge of these phenomena provides insights into the characteristics of the infection, which can help implement appropriate infection control measures. To obtain a more complete picture of RHD caused by different GI.1 strains, it is necessary to correlate the genetic diversity within L. europaeus/GI.1 strains and the immune picture in response to infection. We performed a phylogenetic analysis of the L. europaeus/GI strains and compared the recombinant L. europaeus/GI.1 strain with the GI.1a strain on the basis of a thorough statistical analysis of immunological traits performed previously. Our phylogenetic analysis based on the sequence of the gene encoding the VP60 capsid protein of 34 strains of Lagovirus europaeus showed that the Hartmannsdorf strain forms a separate clade from the other GI.1a strains and is separate from the GI.1b-d strains. Next, we showed significant differences in the levels of individual parameters for non-specific cellular and humoral immunity in infection with the GI.1a strain and the Hartmannsdorf recombinant strain. Against the background of this study, our results indicate that the characteristics of each recombinant should be considered individually., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant changes in cervicovaginal microbiota composition. The objective of our study was to characterize the cervicovaginal microbiota of women undergoing hysterectomy due to benign disease, atypical hyperplasia, and endometrial cancer; The study included 96 patients, who undergone surgical treatment due to benign uterine disease, precancerous endometrial lesion, and endometrial cancer. Quantitative and qualitative real-time PCR analysis of DNA isolated from vaginal fornix and endocervical canal samples was performed to detect the 19 most commonly identified microorganisms, including different Lactobacillus spp., Atopobium , Bifidobacterium , Chlamydia , and Gardnerella ; At least one of the tested microorganisms was identified in 88.5% of vaginal and 83.3% of cervical samples. Lactobacillus iners was significantly more frequent in patients with benign condition, whereas Dialister pneumosintes and Mobiluncus curtisii was more frequent in cancer patients; Mobiluncus curtisi and Dialister pneumosintes, which were identified as significantly more common in endometrial cancer vaginal samples, may be considered as potential endometrial cancer co-factors which promote/stimulate carcinogenesis. However, the exact mechanism of such activity remains unexplained and requires further investigations.

Gastric cancer is one of the five most common types of cancer worldwide. Due to the heterogeneous course and the involvement of many risk factors, its treatment and diagnosis is an important challenge for modern medicine. Recent studies have emphasized the i role of Toll-like receptors (TLRs) expressed on selected cells of the immune system in the pathogenesis of gastric cancer. The aim of this study was to determine the prevalence of TLR2 on T lymphocytes, B lymphocytes, monocytes, and dendritic cells in patients diagnosed with gastric cancer, with particular emphasis on the stage of the disease. Based on the obtained results, we have shown that patients with gastric cancer are characterized by a higher percentage of all tested populations of peripheral blood immune cells expressing TLR2 in relation to patients from the control group. Moreover, a detailed analysis of the collected results showed a significant link between TLR2 and the stage of the disease.

The purpose of this study was to evaluate the phytochemical profiles of the seeds, sprouts, leaves, flowers, roots and herb of Salvia hispanica and to demonstrate their significant contribution to antioxidant and antimicrobial activities. Applied methods were: HPLC-DAD coupled with post-column derivatization with ABTS reagent, untargeted metabolomics performed by LC-Q-Orbitrap HRMS, and two-fold micro-dilution broth method, which involved suspending a solution of tested compounds dissolved in DMSO in Mueller-Hinton broth for bacteria or Mueller-Hinton broth with 2% glucose for fungi. Metabolomic profiling using LC-Q-Orbitrap HRMS used in this study yielded the identification and preliminary characterization of one hundred fifteen compounds. The dominant class of compounds was terpenoids (31 compounds), followed by flavonoids (21 compounds), phenolic acids and derivatives (19 compounds), organic acids (16 compounds) and others (fatty acids, sugars and unidentified compounds). The organic and phenolic acids were the most abundant classes in terms of total peak area, with distribution depending on the plant raw materials obtained from S. hispanica. The main compound among this class for all types of extracts was rosmarinic acid which was proven to be the most abundant for antioxidant potential. All tested extracts exhibited considerable antibacterial and antifungal activity. The strongest bioactivity was found in leaf extracts, which presented bactericidal activity against Gram-positive bacteria ( S. aureus , S. epidermidis , M. luteus and E. faecalis ). The work represents the first compendium of knowledge comparing different S. hispanica plant raw materials in terms of the profile of biologically active metabolites and their contribution to antioxidant, antimicrobial and antifungal activity.

Chronic lymphocytic thyroiditis, commonly known as HD, is one of the most common thyroid disorders. Due to the diverse factors affecting the etiopathogenesis of this disease (hormonal disorders and genetic and environmental factors), as well as the direct involvement of the immune system, scientists are increasingly willing to undertake research aimed at explaining the impact of the loss of immune tolerance and reactivity of autoantigens on the development of the disease. One of the directions of research in recent years is the role of the innate immune response, particularly Toll-like receptors (TLRs), in the pathogenesis of HD. The purpose of this study was to determine the importance of Toll-like receptor 2 (TLR2) expression on selected populations of immune cells, namely, monocytes (MONs) and dendritic cells (DCs), in the course of HD. Particular attention was paid to the analysis of TLR2's correlation with clinical parameters and the possibility its use as a potential biomarker molecule in the diagnostic process. Based on the obtained results, we found a statistically significant increase in the percentage of all analyzed populations of immune cells, i.e., mDC BDCA-1+CD19-, pDC BDCA-1+CD123, classical MONs CD14+CD16-, and non-classical MONs CD14+CD16+ showing on their surface TLR2 expression in patients diagnosed with HD compared to the healthy volunteers. Moreover, in the study group, we noted a more than 6-fold increase in the concentration of the soluble form of TLR2 in plasma compared to healthy patients. In addition, the correlation analysis showed significant positive correlations between the level of TLR2 expression on selected subpopulations of immune cells and biochemical indicators of thyroid function. Based on the obtained results, we can assume that TLR2 may be involved in the immunopathogenesis of HD.

Three new crystal structures of 1 H -benzo[ d ]imidazole derivatives were determined. In the structures of these compounds, an identical system of hydrogen bonds, C(4), was observed. Solid-state NMR was applied for testing the quality of the obtained samples. All of these compounds were tested for in vitro antibacterial activity against Gram-positive bacteria and Gram-negative bacteria, as well as antifungal activity, by checking their selectivity. ADME calculations indicate that the compounds can be tested as potential drugs.

Helicobacter pylori ( H. pylori ) is considered the most common bacterial pathogen colonizing stomach mucosa of almost half the world's population and is associated with various gastrointestinal diseases (from digestive problems and ulcers to gastric cancer). A lack of new drugs and a growing number of H. pylori antibiotic-resistant strains is a serious therapeutic problem.As a mixture of natural compounds, propolis has antimicrobial activity based on high concentrations of bioactive polyphenols (mainly flavonoids and phenolic acid derivates). The chemical composition of tested Georgian propolis is characterized by the presence of flavonoids aglycones, and phenolic acid monoesters, e.g., pinobanksin-5-methyl ether, pinobanksin, chrysin, pinocembrin, galangin, pinobanksin-3- O -acetate, pinostrobin and pinobanksin-3- O -butanoate, or isobutanoate and methoxycinnamic acid cinnamyl ester. The anti- H. pylori activity of 70% ethanol water extracts of 10 Georgian propolis samples was evaluated in vitro by MIC (minimal inhibitory concentration) against the reference strain ( H. pylori ATCC 43504) and 10 clinical strains with different antibiotic-resistance patterns. The strongest anti- Helicobacter activity (MIC and MBC = 31.3 µg/mL) was observed for propolis from Orgora, Ota, and Vardzia and two from Khaheti. Lower levels of activity (MIC = 62.5 µg/mL) were found in propolis obtained from Qvakhreli and Pasanauri, while the lowest effect was observed for Norio and Mestia (MIC = 125.0 µg/mL). However, despite differences in MIC, all evaluated samples exhibited bactericidal activity. We selected the most active propolis samples for assessment of urease inhibition property. Enzyme activity was inhibited by propolis extracts, with IC 50 ranging from 4.01 to 1484.8 µg/mL. Principal component analysis (PCA) and hierarchical fuzzy clustering (dendrograms) coupled with matrix correlation analysis exhibited that the strongest anti- Helicobacter activity was connected with black poplar origin and high flavonoid content of propolis. Samples with lower activity contained higher presence of aspen markers and/or dominance of non-flavonoid polyphenols over flavonoids. In summary, Georgian propolis can be regarded as a source bioactive compounds that can be used as adjuvant in therapy of H. pylori infection.

In this study, six new 2,6-disubstituted thiosemicarbazone derivatives of pyridine were synthesized (4−9), and their tuberculostatic activity was evaluated. All of them showed two- to eightfold higher activity (minimum inhibitory concentration (MIC) 0.5−4 µg/mL) against the resistant strain compared with the reference drug. Compounds 5 and 7, which contained the most basic substituents—pyrrolidine and piperidine—in their structure, strongly inhibited the growth of the standard strain (MIC 2 µg/mL). Furthermore, the same derivatives exhibited activity comparable to that of the reference drugs against some types of Gram-positive bacteria (MIC 0.49 µg/mL) and showed no cytotoxicity (IC50 > 50 µg/mL) in HaCaT cells. The zwitterionic structure of each compound was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion analyses showed that all compounds are good drug candidates. Thus, compounds 5 and 7 were identified as leading structures for further research on antituberculosis drugs with extended effects.

Propolis (bee glue) is a resinous substance produced by different species of bees i.a. from available plant resins, balsams, and exudates. It is characterized by significant biological activity (e.g., antimicrobial and antioxidant) and phytochemical diversity related to the available plant sources in specific geographical regions. The available scientific literature on propolis is quite extensive; however, there are only a few reports about propolis originating from Georgia. Therefore, our research was focused on the characterization of Georgian propolis in terms of phytochemical composition and antimicrobial/antioxidant activity. Performed research included UHPLC-DAD-MS/MS phytochemical profiling, determination of total phenolic and flavonoid content, antiradical and antioxidant activity (DPPH and FRAP assays) as well as antibacterial activity of propolis extracts obtained using 70% ethanol (70EE). Georgian propolis extracts exhibited strong activity against Gram-positive bacteria (22 mm-disc assay/64 µg/mL-MIC for S. aureus , sample from Imereti) and weaker against Gram-negative strains as well as strong antioxidant properties (up to 117.71 ± 1.04 mgGAE/g in DPPH assay, up to 16.83 ± 1.02 mmol Fe 2+ /g in FRAP assay for samples from Orgora and Qvakhreli, respectively). The phytochemical profile of Georgian propolis was characterized by the presence of flavonoids, free phenolic acids, and their esters. In most of the samples, flavonoids were the main chemical group (52 compounds), represented mainly by 3- O -pinobanksin acetate, pinocembrin, chrysin, galangin, and pinobanksin. The primary plant precursor of the Georgian bee glue is black poplar ( Populus nigra L.) while the secondary is aspen poplar ( P. tremula L.).