Gender Influences Gut Microbiota among Patients with Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease that affects approximately 11% of the general population. The gut microbiota, among other known factors, plays a substantial role in its pathogenesis. The study aimed to characterize the gut microbiota differences between patients with IBS and unaffected individuals, taking into account the gender aspect of the patients and the types of IBS determined on the basis of the Rome IV Criteria, the IBS-C, IBS-D, IBS-M, and IBS-U. In total, 121 patients with IBS and 70 unaffected individuals participated in the study; the derived stool samples were subjected to 16S rRNA amplicon sequencing. The gut microbiota of patients with IBS was found to be more diverse in comparison to unaffected individuals, and the differences were observed primarily among Clostridiales, Mogibacteriaceae, Synergistaceae, Coriobacteriaceae, Blautia spp., and Shuttleworthia spp., depending on the study subgroup and patient gender. There was higher differentiation of females' gut microbiota compared to males, regardless of the disease status. No correlation between the composition of the gut microbiota and the type of IBS was found. Patients with IBS were characterized by more diverse gut microbiota compared to unaffected individuals. The gender criterion should be considered in the characterization of the gut microbiota. The type of IBS did not determine the identified differences in gut microbiota.

Differences in the composition of the bacterial element of the urinary tract microbiome in patients undergoing dialysis and patients after kidney transplantation.

Introduction: The development of molecular biology methods and their application in microbial research allowed the detection of many new pathogens that cause urinary tract infections (UTIs). Despite the advances of using new research techniques, the etiopathogenesis of UTIs, especially in patients undergoing dialysis and patients after kidney transplantation, is still not fully understood. Methods: This study aimed to characterize and compare the composition of the bacterial element of the urinary tract microbiome between the groups of patients undergoing dialysis (n = 50) and patients after kidney transplantation (n = 50), with positive or negative urine culture, compared to healthy individuals (n = 50). Results: Asymptomatic bacteriuria was observed in 30% of the urine cultures of patients undergoing dialysis and patients after kidney transplantation, with Escherichia coli as the most dominant microorganism (73%) detected with the use of classical microbiology techniques. However, differences in the bacterial composition of the urine samples between the evaluated patient groups were demonstrated using the amplicon sequencing. Finegoldia, Leptotrichia, and Corynebacterium were found to be discriminative bacteria genera in patients after dialysis and kidney transplantation compared to the control group. In addition, in all of urine samples, including those without bacteriuria in classical urine culture, many types of bacteria have been identified using 16S rRNA sequencing. Discussion: The revealed microbial characteristics may form the basis in searching for new diagnostic markers in treatment of patients undergoing dialysis and patients after kidney transplantation.

More Than Resveratrol: New Insights into Stilbene-Based Compounds.

The concept of a scaffold concerns many aspects at different steps on the drug development path. In medicinal chemistry, the choice of relevant "drug-likeness" scaffold is a starting point for the design of the structure dedicated to specific molecular targets. For many years, the chemical uniqueness of the stilbene structure has inspired scientists from different fields such as chemistry, biology, pharmacy, and medicine. In this review, we present the outstanding potential of the stilbene-based derivatives. Naturally occurring stilbenes, together with powerful synthetic chemistry possibilities, may offer an excellent approach for discovering new structures and identifying their therapeutic targets. With the development of scientific tools, sophisticated equipment, and a better understanding of the disease pathogenesis at the molecular level, the stilbene scaffold has moved innovation in science. This paper mainly focuses on the stilbene-based compounds beyond resveratrol, which are particularly attractive due to their biological activity. Given the "fresh outlook" about different stilbene-based compounds starting from stilbenoids with particular regard to isorhapontigenin and methoxy- and hydroxyl- analogues, the update about the combretastatins, and the very often overlooked and underestimated benzanilide analogues, we present a new story about this remarkable structure.

Synthesis and Antibacterial Activity of New N-Alkylammonium and Carbonate-Triazole Derivatives within Desosamine of 14- and 15-Membered Lactone Macrolides.

Desosamines of azithromycin (AZM) and clarithromycin (CLA) were modified by N-alkylation or nucleophilic substitution at the carbonyl/CuAAC sequence. Biological studies revealed a higher antibacterial potency of quaternary N-alkylammonium bromides of CLA as compared to AZM. SAR studies of CLA salts, including biological, conformation and molecular-docking analysis, enriched by physicochemical parameters, showed the importance of less bulky and unsaturated substituent for an efficient docking mode at the ribosomal tunnel and good antibacterial potency against clinical and standard Streptococcus pneumoniae and Streptococcus pyogenes strains (MICs 0.25 or 0.5 µg/mL). These CLA salts also have an at least threefold lower cytotoxicity than reference antibiotics at comparable antibacterial activity against the S. pneumoniae clinical strain. Differences in antibacterial effects noted for AZM and CLA salts bearing less bulky N-substituents can be better understood when their binding modes in the ribosomal tunnel are considered rather than their common low lipophilicity and excellent water solubility.

Time and spatial variability in concentrations of selected metals and their species in water and bottom sediments of Dzierzno Duze (Poland).

Poland is an industrialized country in which industries (especially the heavy ones) have had a tremendous influence on the environment. It is particularly visible in the Upper Silesia region, where the observed air, soil and water pollution levels are the most highest. The aim of this study was to determine the time and spatial variability in: concentrations of selected metals (Co, Ni, Zn, Cr, Mn, Pb, Cd), and, to a limited extent, of Cu, V, Al and Sr; concentrations of inorganic ions (Cl-, SO42-, Na+, K+, Ca2+ and Mg2+) and values of pH, conductivity and redox potential. The enlisted parameters were determined for the water and bottom sediments of Dzierzno Duze, a water reservoir located in Poland (Upper Silesia region). Additionally, fractions of a few characteristic metals were determined in the bottom sediments of the discussed reservoir with the BCR method. The investigation was carried out in 2017. It showed that the reservoir surface water was not polluted with the determined metal contents. However, it was highly polluted with the inorganic ions. The metal contents determined in the bottom sediments were high. If the conditions for releasing them from the bottom sediments had been favorable, this situation could have posed a potentially considerable environmental threat.

Synthesis, docking and antibacterial studies of more potent amine and hydrazone rifamycin congeners than rifampicin.

New rifamycin congeners (1-33) with incorporated amine and hydrazone substituents leading to lipophilic and/or basic nature and altered rigidity of modified C(3) arm were synthesized and structurally characterized in detail. NMR spectroscopic studies at different temperatures indicate two types of structures of rifamycin congeners that are realized in solution: zwitterionic and non-ionic forms in dependence of the basicity of modified C(3) arm. The presence of rifamycin congeners in these two possible forms has a significant impact on the physico-chemical parameters such as lipophilicity (clogP) and water solubility and different binding mode of the C(3) arm of antibiotic at RNAP binding pocket (molecular target) leading to different antibacterial potency. The highest antibacterial potency against S. aureus (including MRSA and MLSB strains) and S. epidermidis strains, even higher than reference rifampicin (Rif) and rifaximin (Rifx) antibiotics, was found for rifamycin congeners bearing at the C(3) arm relatively rigid and basic substituents (bipiperidine and guanidine groups). These modifications provide favorable docking mode and excellent water solubility resulting in high potency (MICs 0.0078 µg/mL what gives ∼ 8.5 nM), irrespective whether rifamycin congener is a tertiary amine (15) or hydrazone (29). In turn, for a higher antibacterial potency of rifamycin congeners against E. faecalis strain (MICs 0.5 µg/mL that is 0.6 µM) as compared to Rif and Rifx, the most crucial factors are: bulkiness and the lipophilic character of the end of the C(3) rebuilt arm.

Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing.

The influence of an inorganic support - halloysite nanotubes - on the release rate and biological activity of the antibiotic encapsulated in alginate-based dressings was studied. The halloysite samples were loaded with approx. 10 wt.% of the antibiotic and then encapsulated in Alginate and Gelatin/Alginate gels. The material functionalized with aliphatic amine significantly extended the release of vancomycin from alginate-based gels as compared to that achieved when silica was used. After 24 h, the released amounts of the antibiotic immobilized at silica reached 70%, while for the drug immobilized at halloysite the released amount of vancomycin reached 44% for Alginate discs. The addition of gelatin resulted in even more prolonged sustained release of the drug. The antibiotic was released from the system with a double barrier with Higuchi kinetic model and Fickian diffusion mechanism. Only the immobilized drug encapsulated in Alginate gel demonstrated very good antimicrobial activity against various bacteria. The inhibition zones were greater than those of the standard discs for the staphylococci and enterococci bacteria tested. The addition of gelatin adversely affected the biological activity of the system. The inhibition zones were smaller than those of the reference samples. A reduction in the drug dose by half had no significant effect on changing the release rate and microbiological activity. The in vivo toxicity studies of the material with immobilized drug were carried out with Acutodesmus acuminatus and Daphnia magna. The material studied had no effect on the living organisms used in the bioassays. The proposed system with a double barrier demonstrated high storage stability.

16-Membered Macrolide Lactone Derivatives Bearing a Triazole-Functionalized Arm at the Aglycone C13 Position as Antibacterial and Anticancer Agents.

A series of new C13-triazole-bridged and C13-ether leucomycin analogues with a reduced aldehyde group were synthesized. Derivatives with the highest antibacterial [MIC values (S. epidermidis, S. pneumoniae): ∼2-4 µg mL(-1) ; 2.55-5.09 µm] and cytotoxic [IC50 values (HeLa, KB, MCF-7, A549, HepG2 cells): ∼1.35-3.70 µm] potencies were those with the best aqueous solubility and bearing a saccharide-triazole arm at the C13 position of the aglycone. These derivatives preferentially bind at the ribosomal tunnel and show the most attractive selectivity indexes [SI; calculated relative to the human dermal fibroblast (HDF) cell line], even higher than that of the reference compound cytarabine. Results of molecular docking studies of this type of macrolide antibiotics at the ribosomal tunnel, together with experimentally determined lipophilicity and aqueous solubility values, as well as biological assay data revealed the importance of the introduced functional group at the aglycone C13 arm to the future design of anticancer and antibacterial drug candidates. Our results clearly indicate that the high antibacterial and anticancer activities of these types of macrolides do not necessarily depend on the presence of the aldehyde group at the aglycone lactone ring.

Synthesis, structure and antimicrobial evaluation of a new gossypol triazole conjugates functionalized with aliphatic chains and benzyloxy groups.

Synthetic limitations in the copper-catalyzed azide alkyne cycloaddition (CuAAC) on gossypol's skeleton functionalized with alkyne (2) or azide (3) groups have been indicated. Modified approach to the synthesis of new gossypol-triazole conjugates yielded new compounds (24-31) being potential fungicides. Spectroscopic studies of triazole conjugates 24-31 have revealed their structures in solution, i.e., the presence of enamine-enamine tautomeric forms and π-π stacking intramolecular interactions between triazole arms. Biological evaluation of the new gossypol-triazole conjugates revealed the potency of 30 and 31 derivatives, having triazole-benzyloxy moieties, comparable with that of miconazole against Fusarium oxysporum. The results of HPLC evaluation of ergosterol content in different fungi strains upon treatment of gossypol and its derivatives enabled to propose a mechanism of antifungal activity of these compounds.

Structure-activity relationship studies of new rifamycins containing l-amino acid esters as inhibitors of bacterial RNA polymerases.

New rifamycins (1-12) combined with different l-amino acids, containing methyl, ethyl, tert-butyl and benzyl groups at the ester part, via amine linkage, were synthesized and their structures in solution were determined by spectroscopic FT-IR and 1D and 2D NMR methods as well as visualized by DFT calculations. Two types of rifamycin structures were detected in solution: a zwitterionic one with the transferred proton from O(8)H phenol to secondary N(38) atom and a pseudocyclic structure stabilized via formation of intramolecular H-bond within the protonated basic C(3)-substituent. The presence of these rifamycins' structures influenced physico-chemical (logP, solubility) parameters and antibacterial properties. The bulkiness at the ester substituent of new rifamycins containing aromatic l-amino acids was found to be an important factor, besides the solubility, to achieve relatively high antibacterial activity against reference S. epidermidis and reference S. aureus and MRSA strains (MICs 0.016-0.063 µg/mL), comparable to that of rifampicin. SAR for the novel derivatives was discussed in view of the calculated structures of rifamycin-RNAP complexes.