Bridelia species have been used in traditional African medicine for the management of diverse human ailments. In the current work, the detailed phytochemical profiles of the extracts of the stem bark of B. speciosa were evaluated and the antioxidant and enzyme inhibitory properties of the extracts were assessed. The anti-bacterial and anti-mycotic effects of the extracts were evaluated against selected pathogen strains. Additionally, the anti-proliferative effects were studied on the liver cancer HepG2 cell line. Finally, the putative protective effects were assessed on isolated rat liver that was challenged with lipopolysaccharide (LPS). The results revealed the presence of 36 compounds in the ethyl acetate extract, 44 in the methanol extract, and 38 in the water extract. Overall, the methanol extract showed the highest antioxidant activity, particularly in LPS-stimulated rat liver. Additionally, this extract exerted the highest antimycotic effect on C. albicans, whereas the water extract showed a promising anti-proliferative effect on liver cancer HepG2 cells. The methanol extract was also the most active as enzyme inhibitor, against acetylcholinesterase and butyrylcholinesterase. The current study appraises the antioxidant and enzyme inhibition properties of B. speciosa methanol extract and showed that this specie could be a promising source of biologically active phytochemicals, with potential health uses.

Anisakiasis is a human parasitic infection of the gastrointestinal tract that can cause severe abdominal pain, malnutrition, and vomiting. This parasitosis is mainly caused by larvae of the nematode Anisakis simplex, that reach the intestine through the consumption of raw and undercooked seafood, namely fish and cephalopods. Generally, it is undetected, but can sometimes be responsible for severe allergic reactions, namely anaphylaxis, caused by the production of immunoglobulin E in response to chemicals released by the dead larvae in the intestine. To date, no effective drug has been found against this digestive parasitosis and common anthelmintic treatments seem not be active against A. simplex. Essential oils (EOs) present a still fairly unexplored source for natural products with activity towards this parasite. The present work reviews the available literature on EOs tested in vitro against Anisakis nematodes, and compiles the EO composition and activity of the most active.

Over one dozen plant species were used as sources for the active EOs, mainly from Asteraceae, Lamiaceae, Apiaceae and Myrtaceae families. The lowest half maximal lethal concentrations (LC₅₀) were reported for Origanum syriacum and O. compactum EOs, both rich in the monoterpenoid carvacrol (83% and 50%, respectively. The EOs extracted from Tagetes minuta and Nepeta cataria were reported to be the fastest acting, with half maximal lethal times (LT₅₀) under 4 h, and were rich in the oxygenated monoterpene geraniol (55%) and the monoterpenic hydrocarbons β-ocimene (36%) and limonene (27%), respectively. Given their complex chemical composition, additive, synergistic and antagonistic interactions between EO compounds can be responsible for EO activity against this parasite.

A deeper analysis of the chemical structures active against Anisakis, and the nature of their interactions can be possible with further studies on this parasitosis.

The incidence of chronic wounds (CW) is growing at an accelerated rate around the world, becoming a huge burden on healthcare and social systems. CW are characterized for failing to progress through the orderly phases of the healing process, establishing in a self-perpetuating inflammatory stage getting predisposed to infections, resulting in long-term morbidity and mortality. To address this problem, wound dressings with a new intricated nano-architecture and functionalized with active biomolecules are being developed to treat CW. The introduction of peptides with renown antimicrobial capacities, as pexiganan (or MSI-78), which display a broad spectrum of antibacterial activity and capacity to reduce bacterial resistance, has been considered a viable solution. Tiger 17, a not so explored peptide with improved regenerative potential is also being investigated to unveil its antimicrobial potential so far unknown. In this study, combinations of poly(vinyl alcohol) (PVA) and cellulosic compounds, such as cellulose acetate (CA) and cellulose nanocrystalline (CNC), were processed via electrospinning to give rise to porous, highlight intricate and flexible, biocompatible, biodegradable, and mechanically stable mats and, then, modified with combinations of pexiganan and Tiger 17. PVA/CA and PVA/CNC mats were prepared at different ratios and submitted to crosslinking process to avoid their instant solubilization in aqueous media. Antimicrobial efficacy of pexiganan and Tiger 17 was evaluated against Pseudomonas aeruginosa. The biomolecules were initially screened for their antibacterial efficacy by the determination of minimal inhibitory concentrations (MICs). Mats were modified with pexiganan at 2xMIC (60 µg/mL) and with Tiger 17 at twice the concentration required to induce regenerative effects (40 µg/mL). The Mal-PEG2-OH spacer was used as a binding agent. Data revealed the ability of the peptide-modified surfaces to fight P. aeruginosa infection above the unaltered mats, demonstrating the potential of this strategy for CW care.

Natural products (NPs), being evolutionary selected over millions of years to bind to biological macromolecules, remain an important source of inspiration for medicinal chemists even after the advent of efficient drug discovery technologies such as combinatorial chemistry and high-throughput screening. Thus, there is a strong demand for efficient and user-friendly computational tools that allow to analyze large libraries of NPs. In this context, we present NP Navigator – a free, intuitive online tool for visualization and navigation through the chemical space of NPs and NP-like molecules^[1] (https://infochm.chimie.unistra.fr/npnav/chematlas_userspace ). It is based on the hierarchical ensemble of more than 200 Generative Topographic Maps(GTM)^[2], featuring NPs from the COlleCtion of Open NatUral producTs (COCONUT), bioactive compounds from ChEMBL and commercially available molecules from ZINC. NP Navigator allows to efficiently analyze different aspects of NPs - chemotype distribution, physicochemical properties, reported and/or predicted biological activity and commercial availability of NPs. Users are welcome not only to browse through hundreds of thousands of compounds from ZINC, ChEMBL and COCONUT but also project a several external molecules that play the role of “chemical trackers” allowing to trace particular chemotypes in the NP chemical space and detect analogs of the compound of interest.

[1] Y. Zabolotna, P. Ertl, D. Horvath, F. Bonachera, G. Marcou, A. Varnek, NP Navigator: a New Look at the Natural Product Chemical Space, 2021.
[2] C. M. Bishop, M. Svensén, C. K. I. Williams, Neural Comput. 1998, 10, 215-234.

According to The Organization for Economic Cooperation and Development (OECD), 2.4 million people in Europe, North America and Australia may die in the next 30 years from infections caused by resistant microorganisms. S. aureus – a opportunistic pathogen resistant to multiple antibiotics – induced infections are among the most prevalent bacterial infections, being on the front of the line of the World Health Organization (WHO) concerns. In this study, we report the production of biodegradable microfibers composed of sodium alginate (SA) and gelatin (GN), via wet-spinning technique, and their subsequent functionalization via adsorption with Nisin Z. Nisin Z is an antimicrobial peptide which possess great antibacterial activity (mainly against Gram-positive bacteria) and low toxicity in humans, thus being a great candidate for the production of scaffolds with S. aureus eradication ability for infected wounds. SA/GN microfibers were successfully extruded at a 70/30% v/v polymer ratio, within a calcium chloride (CaCl₂) 2wt% coagulation bath. SA-free fibers were obtained through chemical modification (PBS concentrated solutions and subsequently, SAGN and SA-free fibers were crosslinked with glutaraldehyde (labeled as SAGNCL and GNCL, respectively). Finally, Nisin Z was functionalized onto the fibers at an average concentration of 178µg/mL. Fibers were characterized via Fourier transform infrared spectroscopy, thermal analysis and brightfield microscopy. Nisin Z degradation/release profiles (SBF, 28 days) were assessed. Antibacterial activity against S. aureus was detected via time-kill kinetics assessments. SAGNCL and GNCL loaded microfibers were capable of inhibit the grow of S. aureus up to 99% after 48 h of culture. The SA and SAGN loaded microfibers were not as effective, losing their action after 6 h. Bacteria elimination was consistent with the release kinetics of Nisin Z from the fibers. Overall, data revealed the potential of Nisin Z in fighting S. aureus-induced infections, while loaded onto biodegradable crosslinked polymeric scaffolds.

Organism’s hypoxia tolerance depends on many factors, including age. High newborn organism’s tolerance and high level of oxidative stress throughout aging were demonstrated by many studies. However, there is still lack of investigations, reflecting the intensity of systemic inflammatory response in different age organisms in correlation to hypoxia tolerance. The aim of study was to determine the relationship between age-related tolerance to hypoxia, HIF-1 and PHD2 (prolyl hydroxylase domain protein) expression levels and the intensity of systemic inflammatory response in newborn, prepubertal and adult Wistar rats. In case of investigation the tolerance to hypoxia, rats were placed into a decompression chamber at altitude simulation of 11,500 m. It was demonstrated that prepubertal rats are the least tolerant to hypoxia and newborns are the most tolerant. Newborn rats are characterized by high mRNA Hif-1α expression level in the liver, accompanied by low content of HIF-1 protein and high level of PHD2. The growth in HIF-1α protein level throughout the age is accompanied by the growth of pro-inflammatory cytokines level. Prepubertal animals are the least hypoxia tolerant and their HIF-1α mRNA expression level was higher than in adult animals. The PHD2 activity in prepubertal animals was significantly reduced in comparison to newborn rats, and the HIF-1α protein level was not changed. The lowest tolerance of the prepubertal males to hypoxia correlated with the greatest manifestations of hepatic inflammation and elevated endotoxin, neopterin, and C-reactive protein levels in LPS-induced systemic inflammatory response. The growth of serum HIF-1α in 3 h after LPS injection was observed only in prepubertal rats. The obtained data should be taken into account during the development of therapeutic strategy for prepubertal children with infectious and inflammatory diseases.

Infected diabetic foot ulcers (DFUs) are a frequent complication of diabetes, with limb amputation being highly prevalent worldwide. Staphylococcus aureus and Pseudomonas aeruginosa are the main microbial inhabitants of infected DFUs, often gaining antimicrobial-resistance[1]. Nanoparticle (NP)-mediated therapies may overcome this problem, as they are able to carry, protect and release the load(s) in a controlled manner[2, 3]. As payloads, Essential oils (EOs) exert quick and strong bactericidal action. Eugenol, in particular, is an amphipathic hydroxyphenyl propene, highly bactericidal towards these pathogens[1]. This work proposes EO-encapsulation into polyelectrolyte complexed (PEC) NPs fabricated with quaternized cellulose (QC) and carboxymethyl lignin (CML)[4]. The presence of a peak at 1482 cm^-1 in Fourier-transform infrared spectroscopy (FTIR) spectra showcased vibrations of methyl groups of cationic quaternary amines grafted into the cellulose chain, while two absorption bands at 1645 cm^-1 and 1417 cm^-1 emphasized the introduction of negatively charged carboxyl groups into lignin’s skeletal bonds. Minimum inhibitory concentrations (MIC) of cinnamon leaf oil (CLO) and clove oil (CO) EOs were previously established against reference strains of S. aureus and P. aeruginosa. The MIC values were 0.82 mg/mL and 0.83 mg/mL for CLO and 39.3 mg/mL and 52.8 mg/mL for CO, respectively[1]. At optimized conditions, EOs were added at MIC to the anionic polyion (CML) before complexation, then added to the polycation (QC) and ultrasonicated to form EO-loaded QC/CML PEC NPs. The loading efficiency of dialysis-purified NP dispersions was monitored by UV-Vis, being 83% for QC/CML/CLO NPs and 12% for QC/CML/CO NPs. Bright-field and fluorescence microscopy (using Nile Red) confirmed the formation of EO-PEC NPs. Antimicrobial activity of loaded PEC NPs was confirmed through agar diffusion and time-kill kinetics assays[1]. Preliminary data pointed to the potential of EO-loaded PECs to work as a therapeutic alternative to fight some of the pathogens colonizing DFUs.

The global emerging infectious diseases caused by multi-drug resistant (MDR) bacteria necessitates worldwide systematic efforts to discover new effective antibacterial agents, replacing traditional antibiotics no longer active. For this purpose, we recently synthetized amino acid-modified cationic dendrimers and ammonium hydrochloride copolymers and evaluated their antibacterial activity on several MDR clinical isolates. As natural antibacterial peptides (AMPs), the prepared cationic macromolecules were capable to electrostatically interact with the membranes of pathogens, causing irreversible damage and inhibition of bacterial growth, regardless of their resistance to most conventional antibiotics. The dendrimers, depending on their amino acid composition, the number of cationic groups and the structure of the internal matrix, showed a target specific antibacterial activity. Indeed, those containing lysine and/or histidine, having 192 cationic groups (N⁺), were active on non-fermenting Gram-negative species. In particular, the G5K dendrimer showed a very low MIC value on P. aeruginosa (2.1 µM), comparable to that of colistin. The arginine and/or lysine dendrimers with 70-136 N⁺ were specifically active on Enterococci and Staphylococci, while the lysine dendrimer, with 128 N⁺, based on the results obtained so far, is active on Acinetobacter (6.3-12.7 µM). Unlike the dendrimers, the copolymers showed MICs as low as 0.6-1.2 µM against several Gram-positive and Gram-negative isolates. In this communication review, we examined the preparation and antibacterial effects of the best performing cationic macromolecules mentioned above. In turbidimetric and 24 hour-killing studies, both the dendrimers and copolymers here examined displayed a rapid bactericidal activity. Thanks to their physicochemical properties, suitable for biomedical applications, and to the observed bactericidal effects, our new cationic dendrimers and copolymers could represent novel tools, with narrow and/or broad-spectrum activity against MDR strains, regardless of their resistance to current antibiotics.

Introduction. Doxorubicin (DOX) is a chemotherapy drug that causes nephrotoxicity in rodent models and, to a lesser extent, in cancer patients. doxorubicin hydrochloride or doxorubicin - loaded poly(lactide-co-glycolide acid) (Dox-PLGA) nanoparticles at a therapeutic dose were injected intravenously male Wistar rats. PLGA is a biodegradable polymer used as a drug delivery vehicle. However, the therapeutic effect of Dox-PLGA is not clearly understood.

The aim of the study. To estimate a comparative assessment of the nephrotoxic effects of different forms of doxorubicin.

Materials and Methods. A study was carried out on male Wistar rats weighing about 200‑250 g (n=24). Morphological assessment of kidneys was performed using light microscopy. Ultrastructural changes were studied using TEM Libra120 transmission electron microscope. The levels of ALT, AST, urea, creatinine in blood serum were determined. Comparison of digital data between experimental groups was performed using the Kruskal-Wallis test (ANOVA). Differences were considered statistically significant at p <0.05.

Results and discussion. Degeneration changes in the proximal tubules with the destruction of the brush border were revealed by light and electron microscopy in the kidneys on the 8th and 21st days of the experiment after the administration of doxorubicin hydrochloride and its nanosomal form Dox-PLGA. It was found that on the 8th day, PLGA-doxorubicin causes less pronounced degenerative changes in the epithelium of the proximal tubules. The short-term effect after administration of Dox-PLGA is characterized by an increase in creatinine levels, and the long-term effect by an increase in the level of ALT activity, as well as the concentrtion of urea and creatinine.

Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule.

A systematic research was performed using the PubMed and ClinicalTrial.gov databases. Articles published up to 2021 meeting the inclusion criteria were investigated. LAG-3 expression has been linked to increased pathology in certain infections, such as the ones caused by Salmonella, Plasmodium parasites, Mycobacterium tuberculosis, human immunodeficiency virus (HIV), non-pathogenic simian immunodeficiency virus (SIV), in hepatitis B virus (HBV), human papillomavirus (HPV), chronic hepatitis C virus (HCV), lymphocytic choriomeningitis virus (LCMV) and herpes simplex virus 1 (HSV-1).

Here, we will discuss the impaired control of cell-mediated immunity associated with high accumulation of LAG-3 after infection, in most cases associated with a high bacterial/viral load, a reduced survival rate or persisting metabolic and inflammation disorders. Interestingly, the in vitro blockade of PD-1/LAG-3 interactions enhanced cytokine production in response to some of these infections.