Search Results (140)

The biological and thermal properties of a class of synthetic dihydroimidazotriazinones were disclosed in this article for the first time. Molecules 1–6—as potential innovative antimetabolites mimicking bicyclic aza-analogues of isocytosine—were evaluated for their in vitro anticancer activity. Moreover, in vivo, in vitro, and ex vivo toxicity profiles of all the compounds were established in zebrafish, non-tumour cell, and erythrocyte models, respectively. Their antihaemolytic activity was also evaluated. Additionally, the thermal decomposition mechanism, path, and key thermal properties of heterocycles 1–6 were analysed. It was found that all the studied compounds revealed significant antiproliferative activities against tumour cells of the lung, cervix, ovary, and breast, as well as acute promyelocytic leukaemia cells, superior or comparable to that of an anticancer agent gemcitabine. Most of them were less toxic to non-tumour cells than this standard drug, and none had a haemolytic effect on red blood cells. All the tested heterocycles proved to be safer for zebrafish than a standard drug pemetrexed. Some exhibited the ability to inhibit oxidative haemolysis, suggesting their protective action on erythrocytes. The differential scanning calorimetry (DSC) analyses confirmed that all molecules melted within one narrow temperature range, proving their purity. The melting points depended solely on the type of substituent and increased as follows: 4 (R = 3-ClPh) < 2 (R = 4-CH₃Ph) = 3 (R = 4-OCH₃Ph) < 5 (R = 4-ClPh) = 1 (R = Ph) < 6 (R = 3,4-Cl₂Ph). The thermogravimetry/differential thermogravimetry (TG/DTG) studies confirmed high thermal stability of all the investigated heterocycles in inert (>230 °C) and oxidising (>260 °C) atmospheres, which depended directly on the R. The pyrolysis process included one main decomposition stage and was connected with the emission of NH₃, HCN, CH₃CN, HNCO, alkane, alkene, aromatic fragments, CO₂ (for all the compounds), and HCl (for the molecule with 3,4-Cl₂Ph), which was confirmed by FTIR and QMS analyses. In turn, the oxidative decomposition process of the tested polyazaheterocycles took place in two main stages connected with the formation of the same volatiles as those observed in an inert atmosphere and additionally with the release of N₂, NO, CO, and H₂O. These results proved that the pyrolysis and oxidative decomposition run through the radical mechanism connected with the additional reactions between radicals and oxygen in synthetic air. The favourable biological and thermal properties of this class of dihydroimidazotriazinones imply their usefulness as potential pharmaceutics. Full article

Atopic dermatitis (AD) or eczema is an important inflammatory chronic skin disease that brings many complications in its management and treatment. Although several chemical agents are used for treatment, the search for better anti-inflammatory and antibacterial agents of plant origin has been ongoing, since natural compounds, it is commonly believed, are less dangerous than synthetic ones. Therefore, the present study explored a medicinal plant—Eclipta prostrata (L.) L.—for its anti-inflammatory activity alone and in combination with a non-steroidal anti-inflammatory drug (NSAID), diclofenac. The plant extract was used to make a cream formulation for treating atopic dermatitis and as an antibacterial agent against Staphylococcus aures, the major infectious agent associated with AD. The phytochemical analysis of the E. prostrata extract showed the presence of various phytochemicals, including flavonoids, Tannin, saponin, terpenoids, glycosides, phenol, alkaloids, quinone, and protein. The GC-MS profiling of methanolic E. prostrata extract was performed predicted the presence of twenty important phytochemicals, including 2-[5-(2-Hydroxypropyl) oxolan-2-yl]propanoic acid, dl-Menthol, dodecane, undecane, 4,7-dimethyl-, dodecane, 2,6,10-trimethyl-, decane, 2,3,5,8-tetramethyl-, cholest-5-en-3-ol, (3.alpha.)-, TMS derivative, cyclopropane carboxylic acid, 1-hydroxy-, (2,6-di-t-butyl-4-methylphenyl) ester, alpha.-farnesene, propanoic acid, 2-methyl-, 2-ethyl-1-propyl-1,3-propanediyl ester, diethyl phthalate, corticosterone, 2-methylpropionate, hentriacontan-13-ol, O-TMS, phthalic acid, 2,4-dimethylpent-3-yl dodecyl ester, hexasiloxane, 1,1,3,3,5,5,7,7,9,9,11,11-dodecamethyl-, acetic acid, 4-t-butyl-4-hydroxy-1,5-dimethyl-hex-2-ynyl ester, octadecane, 2-methyl- octacosane, 1-iodo-, nonacosane, and eicosyl isopropyl ether. Using an egg albumin denaturation inhibition assay, the anti-inflammatory activities of E. prostrata alone and in combination with diclofenac were investigated, and they showed 93% and 99% denaturation inhibition at 5 mg concentration of E. prostrata in alone and combination with diclofenac, respectively. Heat-induced haemolysis showed 2.5% and 2.4% of haemolysis at 5 mg of E. prostrata alone and in combination with diclofenac, respectively. An MTT assay performed using L₉₂₉ cells proved that the extract has no cytotoxic effect. The plant extract displayed potential antibacterial activity against Staphylococcus aureus; the growth was inhibited at 1 mg/mL of E. prostrata extract. Thus, based on this evidence, the authors suggest that E. prostrata extract should be studied further for its anti-inflammatory and antibacterial activities and topical application in the treatment of atopic dermatitis. Full article

Extracorporeal carbon dioxide removal (ECCO₂R) is an emerging technique designed to reduce carbon dioxide (CO₂) levels in venous blood while enabling lung-protective ventilation or alleviating the work of breathing. Unlike high-flow extracorporeal membrane oxygenation (ECMO), ECCO₂R operates at lower blood flows (0.4–1.5 L/min), making it less invasive, with smaller cannulas and simpler devices. Despite encouraging results in controlling respiratory acidosis, its broader adoption is hindered by complications, including haemolysis, thrombosis, and bleeding. Technological advances, including enhanced membrane design, gas exchange efficiency, and anticoagulation strategies, are essential to improving safety and efficacy. Innovations such as wearable prototypes that adapt CO₂ removal to patient activity and catheter-based systems for lower blood flow are expanding the potential applications of ECCO₂R, including as a bridge-to-lung transplantation and in outpatient settings. Promising experimental approaches include respiratory dialysis, carbonic anhydrase-coated membranes, and electrodialysis to maximise CO₂ removal. Further research is needed to optimise device performance, develop cost-effective systems, and establish standardised protocols for safe clinical implementation. As the technology matures, integration with artificial intelligence (AI) and machine learning may personalise therapy, improving outcomes. Ongoing clinical trials will be pivotal in addressing these challenges, ultimately enhancing the role of ECCO₂R in critical care and its accessibility across healthcare settings. Full article

This study compares three Romanian Hyssopus officinalis species—H. officinalis f. ruber (HOR), H. officinalis f. albus (HOA), and H. officinalis f. cyaneus (HOC)—evaluating their chemical composition and biological activities, specifically protein denaturation, haemolysis inhibition, and antibacterial effects. Chemical profiles were determined using Gas Chromatography–Mass Spectrometry (GC-MS). The species were cultivated at two distinct locations: the Didactic and Experimental Station DESUSVT and the Agricultural Research and Development Station Lovrin (ARDSL). This study investigates the correlation between chemical composition, biological activities, and local climate data at each site. The results show significant variations in chemical profiles, with species and cultivation location influencing the biological activities. H. officinalis f. albus (HOA) exhibited the strongest antimicrobial activity, particularly against Gram-positive bacteria. The molecular docking analysis highlighted key compounds, such as cyclohexene,4-isopropenyl-1-methoxymethoxymethyl and elemol, with binding solid affinities to microbial and inflammatory proteins. This study provides valuable insights into the chemical and biological properties of Hyssopus officinalis, emphasising its potential in combating microbial infections, protein denaturation, and haemolysis inhibition. Full article

SAAP-148, a derivative of LL-37, exhibits a well-defined amphipathic structure and enhanced antimicrobial activity; however, it also displays significant cytotoxicity towards human cells. In this study, we employed Lys-scan to produce a series of amphiphilic SAAP-148 analogs derived from the SAAP-148 sequence to investigate the impact of the distribution of positively charged residues on the biological viability of the antimicrobial peptides (AMPs). The physical properties and biological activity of the designed peptides were subsequently compared. The substitution of lysine resulted in an increase in the overall charge of SAAP-148 and a decrease in its overall hydrophobicity and hyd. moment, except for SAAP-10 where an analogue substitution occurred at the 18th residue. The replacement of lysine led to a reduction in hemolytic activity compared to SAAP-148, with slightly higher haemolysis rates observed in SAAP-11 and SAAP-13. The cytotoxicity of peptides towards human normal lung epithelial cells (BEAS-2B) was closely linked to their haemolytic activity, indicating that substituting lysine may mitigate the cytotoxic effects of SAAP-148. Additionally, the arrangement of positively charged residues in the peptides significantly influenced its antimicrobial activity. Our findings suggest that the positioning of a positively charged residue has a significant impact on the biophysical properties of the peptide. Additionally, the substitution of lysine at different positions demonstrates an influence on the anti-lipopolysaccharide (anti-LPS) activity of SAAP-148. These discoveries provide valuable insights for the design and optimization of antimicrobial peptides, which will be advantageous for the future development of antimicrobial agents. Full article

Malaria is a major international public health problem. The risk of acquiring malaria varies depending on the intensity of transmission and adherence to mosquito precautions and prophylaxis recommendations. Severe malaria can cause significant multiorgan dysfunction, including acute kidney injury (AKI). Intravenous artesunate is the treatment of choice for severe malaria in non-endemic areas. One of the possible events connected with the lifesaving effects of artemisins is post-artesunate haemolysis (PADH), which may be potentially dangerous and under-recognised. We present a case of a seafarer with severe Plasmodium falciparum malaria complicated with AKI and PADH, with a good response to steroid treatment. This case highlights the need for malaria prophylaxis in business travellers, e.g., seafarers to malara-endemic regions, and close supervision of patients with malaria even after the completion of antimalarial treatment due to the possibility of late complications. Full article

Kefiran is a heteropolysaccharide that is considered a postbiotic and is obtained by kefir grains fermented in cow’s milk, while little is known about the donkey milk (DM) variety. Postbiotics are recognised as having important human health benefits that are very similar to probiotics but without the negative effects associated with their ingestion. Donkey is a monogastric animal, as are humans, and when used as an alternative food for infants who suffer from cow milk protein allergies, DM could therefore display more biocompatibility. In this study, the DM kefiran was extracted by ultrasound from kefir grains cultured in donkey milk and fully characterized for its structural and physicochemical properties by Fourier-transform infrared spectroscopy (FT-IR), High-Performance Liquid Chromatography- Refractive Index (HPLC-RI), Scanning electron microscope (SEM), Differential Scanning Calorimeters (DSC) and rheological analyses. In addition, tests were conducted on keratinocytes cell lines and human red blood cells to assess the nontoxicity and haemolysis degree of the polymer. The extraction yield of the DM kefiran was 6.5 ± 0.15%. The FT-IR analysis confirmed the structure of the polysaccharide by showing that the stretching of the C-O-C and C-O bonds in the ring, which formed two bands at 1157 and 1071 cm⁻¹, respectively, and the anomeric band at 896 cm⁻¹ indicates the β configuration and vibrational modes of glucose and galactose. Results were confirmed by HPLC-RI analysis indicating that the ratio glucose/galactose was 1:0.87. Furthermore, the SEM analysis showed a porous and homogeneous structure. The rheological analysis confirmed the pseudoplastic nature of the polymer, while the DSC analysis highlighted excellent thermal resistance (324 °C). Finally, DM kefiran was revealed to have biologically acceptable toxicity, showing a haemolytic activity of less than 2% when using fresh human red blood cells and showing no cytotoxicity on human keratinocytes. Therefore, kefiran obtained by DM shows an excellent biocompatibility, establishing it as a promising polymer for bioengineering human tissue for regenerative applications. Full article

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, potentially life-threatening haematological disease characterised by chronic complement-mediated haemolysis with multiple clinical consequences that impair quality of life. This post hoc analysis assessed haematological and clinical responses to the first targeted complement C3 inhibitor pegcetacoplan in patients with PNH and impaired bone marrow function in the PEGASUS (NCT03500549) and PRINCE (NCT04085601) studies. For patients with impaired bone marrow function, defined herein as haemoglobin <10 g/dL and absolute neutrophil count <1.5 × 10⁹ cells/L, normalisation of the parameters may be difficult. Indeed, 20% and 43% had normalised haemoglobin in PEGASUS and PRINCE, respectively; 60% and 57% had normalised LDH, and 40% and 29% had normalised fatigue scores. A new set of parameters was applied using changes associated with clinically meaningful improvements, namely an increase in haemoglobin to ≥2 g/dL above baseline, decrease in LDH to ≤1.5× the upper limit of normal, and an increase in fatigue scores to ≥5 points above baseline. With these new parameters, 40% and 71% of PEGASUS and PRINCE patients had improved haemoglobin; 60% and 71% had an improvement in LDH, and 60% and 43% had an improvement in fatigue scores. Thus, even patients with impaired bone marrow function may achieve clinically meaningful improvements with pegcetacoplan. Full article

Electrospinning is a widely employed manufacturing platform for tissue engineering applications because it produces structures that closely mimic the extracellular matrix. Herein, we demonstrate the potential of poly(vinyl alcohol) (PVA) electrospun nanofibers as scaffolds for tissue engineering. Nanofibers were created by needleless direct current electrospinning from PVA with two different degrees of hydrolysis (DH), namely 98% and 99% and subsequently heat treated at 180 °C for up to 16 h to render them insoluble in aqueous environments without the use of toxic cross-linking agents. Despite the small differences in the PVA chemical structure, the changes in the material properties were substantial. The higher degree of hydrolysis resulted in non-woven supports with thinner fibres (285 ± 81 nm c.f. 399 ± 153 nm) that were mechanically stronger by 62% (±11%) and almost twice as more crystalline than those from 98% hydrolysed PVA. Although prolonged heat treatment (16 h) did not influence fibre morphology, it reduced the crystallinity and tensile strength for both sets of materials. All samples demonstrated a lack or very low degree of haemolysis (<5%), and there were no notable changes in their anticoagulant activity (≤3%). Thrombus formation, on the other hand, increased by 82% (±18%) for the 98% hydrolysed samples and by 71% (±10%) for the 99% hydrolysed samples, with heat treatment up to 16 h, as a direct consequence of the preservation of the fibrous morphology. 3T3 mouse fibroblasts showed the best proliferation on scaffolds that were thermally stabilised for 4 and 8 h. Overall these scaffolds show potential as ‘greener’ alternatives to other electrospun tissue engineering materials, especially in cases where they may be used as delivery vectors for heat tolerant additives. Full article

Parasite-derived new permeation pathways (NPPs) expressed at the red blood cell (RBC) membrane enable Plasmodium parasites to take up nutrients from the plasma to facilitate their survival. Thus, NPPs represent a potential novel therapeutic target for malaria. The putative channel component of the NPP in the human malaria parasite P. falciparum is encoded by mutually exclusively expressed clag3.1/3.2 genes. Complicating the study of the essentiality of these genes to the NPP is the addition of three clag paralogs whose contribution to the P. falciparum channel is uncertain. Rodent malaria P. berghei contains only two clag genes, and thus studies of P. berghei clag genes could significantly aid in dissecting their overall contribution to NPP activity. Previous methods for determining NPP activity in a rodent model have utilised flux-based assays of radioisotope-labelled substrates or patch clamping. This study aimed to ratify a streamlined haemolysis assay capable of assessing the functionality of P. berghei NPPs. Several isotonic lysis solutions were tested for their ability to preferentially lyse infected RBCs (iRBCs), leaving uninfected RBCs (uRBCs) intact. The osmotic lysis assay was optimised and validated in the presence of NPP inhibitors to demonstrate the uptake of the lysis solution via the NPPs. Guanidinium chloride proved to be the most efficient reagent to use in an osmotic lysis assay to establish NPP functionality. Furthermore, following treatment with guanidinium chloride, ring-stage parasites could develop into trophozoites and schizonts, potentially enabling use of guanidinium chloride for parasite synchronisation. This haemolysis assay will be useful for further investigation of NPPs in P. berghei and could assist in validating its protein constituents. Full article

There is growing evidence that inflammation impairs erythrocyte structure and function. We assessed the impact of mild systemic inflammation on erythrocyte fragility in three different settings. In order to investigate causation, erythrocyte osmotic fragility was measured in mice challenged with a live attenuated bacterial strain to induce low-grade systemic inflammation; a significant increase in erythrocyte osmotic fragility was observed. To gather evidence that systemic inflammation is associated with erythrocyte fragility in humans, two observational studies were conducted. First, using a retrospective study design, the relationship between reticulocyte-based surrogate markers of haemolysis and high-sensitivity C-reactive protein was investigated in 9292 healthy participants of the UK Biobank project. Secondly, we prospectively assessed the relationship between systemic inflammation (measured by the urinary neopterin/creatinine ratio) and erythrocyte osmotic fragility in a mixed population (n = 54) of healthy volunteers and individuals with long-term medical conditions. Both human studies were in keeping with a relationship between inflammation and erythrocyte fragility. Taken together, we conclude that mild systemic inflammation increases erythrocyte fragility and may contribute to haemolysis. Further research is needed to assess the molecular underpinnings of this pathway and the clinical implications in inflammatory conditions. Full article

Ailanthus altissima, an invasive plant species, exhibits pharmacological properties, but also some allergic effects on humans. This study aimed to evaluate the potential toxicity of A. altissima leaves, using a complex approach towards different organisms. The ecotoxic impact of a crude extract was investigated on seeds germination and brine shrimp lethality. Cytotoxicity was studied in vitro using non-target (haemolysis, liposomal model, fibroblast), and target (cancer cells) assays. Leaf extract at 1000 µg/mL significantly inhibited wheat and tomato germination, while no significant effects were found on parsley germination. A slight stimulatory effect on wheat and tomato germination was found at 125 µg/mL. In a brine shrimp-test, the extract showed a low toxicity at 24 h post-exposure (LC₅₀ = 951.04 ± 28.26 μg/mL), the toxic effects increasing with the exposure time and extract concentration. Leaf extract caused low hematotoxicity. The extract was biocompatible with human gingival fibroblasts. No anti-proliferative effect was found within the concentration range of 10–500 µg/mL on malignant melanoma (MeWo) and hepatocellular carcinoma (HepG2). In a liposomal model-test, the extract proved to possess low capability to alter the eukaryotic cell-mimicking membranes within the tested concentration range. Given the low to moderate toxicity on tested organisms/cells, the A. altissima autumn leaves may find useful applications. Full article

Listeria monocytogenes, a foodborne pathogen causing listeriosis, poses substantial societal, economic, and public health challenges due to its resistance, persistence, and biofilm formation in the food industry. Exploring subinhibitory concentrations of compounds to target virulence inhibition and increase susceptibility to adverse conditions presents a promising strategy to mitigate its impact of L. monocytogenes and unveils new potential applications. Thus, this study aims to explore the effect of linalool on virulence factors of L. monocytogenes and potential use in the reduction in its tolerance to stressful conditions. This action was analysed considering the use of two sub-inhibitory concentrations of linalool, 0.312 and 0.625 mg/mL. We found that even with the lowest tested concentrations, a 65% inhibition of violacein production by Chromobacterium violaceum, 55% inhibition in biofilm formation by L. monocytogenes and 62% reduction on haemolysis caused by this bacterium were observed. In addition to its impact on virulence factors, linalool diminished the tolerance to osmotic stress (up to 4.3 log reduction after 24 h with 12% NaCl), as well as to high (up to 3.8 log reduction after 15 min at 55 °C) and low temperatures (up to 4.6 log reduction after 84 days with 12% NaCl at 4 °C). Thus, this study paves the way to further investigation into the potential utilization of linalool to mitigate the threat posed by L. monocytogenes in the field of food safety and public health. Full article

Bee products are considered true wonders of nature, used since ancient times, and studied even today for their various biological activities. In this study, we hypothesise that Romanian bee products from different origins (micro apiary products, lyophilised forms, commercial) exhibit distinct chemical compositions, influencing their biological activities. An LC-MS analysis revealed varied polyphenolic content patterns, with cumaric acid, ferulic acid, rosmarinic acid, and quercitine identified in significant amounts across all samples. Primary anti-inflammatory evaluation phases, including the inhibition of haemolysis values and protein denaturation, unveiled a range of protective effects on red blood cells (RBC) and blood proteins, contingent upon the sample concentration. Antimicrobial activity assessments against 12 ATCC strains and 6 pathogenic isolates demonstrated varying efficacy, with propolis samples showing low efficacy, royal jelly forms displaying moderate effectiveness, and apilarnin forms exhibiting good inhibitory activity, mostly against Gram-positive bacteria. Notably, the lyophilised form emerged as the most promising sample, yielding the best results across the biological activities assessed. Furthermore, molecular docking was employed to elucidate the inhibitory potential of compounds identified from these bee products by targeting putative bacterial and fungal proteins. Results from the docking analysis showed rosmarinic and rutin exhibited strong binding energies and interactions with the putative antimicrobial proteins of bacteria (−9.7 kcal/mol to −7.6 kcal/mol) and fungi (−9.5 kcal/mol to −8.1 kcal/mol). The findings in this study support the use of bee products for antimicrobial purposes in a biologically active and eco-friendly proportion while providing valuable insights into their mechanism of action. Full article

In contemporary times, the sustained aspiration of bioengineering and biomedical applications is the progressive advancement of materials characterized by biocompatibility and biodegradability. The investigation of the potential applications of polymers as natural and non-hazardous materials has placed significant emphasis on their physicochemical properties. Thus, this study was designed to investigate the potential of gelatin–chitosan–moringa leaf extract (G–CH–M) as a novel biomaterial for biomedical applications. The wound-dressing G–CH–M biopolymer was synthesized and characterized. The blood haemolysis, anti-inflammatory, antioxidant, and antibacterial activities of the biopolymer were investigated against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacterial isolates. Our results showed that S. aureus swarming motility was drastically affected. However, the biopolymer had no significant effect on the swarming motility of E. coli. In addition, the biopolymer showed high antibacterial capacities, especially against S. aureus. Plasmid DNA was observed to be effectively protected from oxidative stresses by the biopolymer. Furthermore, the biopolymer exhibited greatly suppressed haemolysis (lower than 2%), notwithstanding the elevated concentration of 50 mg/mL. These results indicated that this novel biopolymer formulation could be further developed for wound care and contamination prevention. Full article