New antibiotics are seen as ‘drugs of last resort’ against virulent bacteria. However, development of resistance towards new antibiotics with time is a universal fact. Delafloxacin (DFX) is a new fluoroquinolone antibiotic that differs from existing fluoroquinolones by the lack of a protonatable substituent, which gives the molecule a weakly acidic nature, affording it higher antibacterial activity under an acidic environment. Furthermore, antibiotic-functionalized metallic nanoparticles have been recently emerged as a feasible platform for conquering bacterial resistance. In the present study, therefore, we aimed at preparing DFX-gold nano-formulations to increase the antibacterial potential of DFX. To synthesize DFX-capped gold nanoparticles (DFX-AuNPs), DFX was used as a reducing and stabilizing/encapsulating agent. Various analytical techniques such as UV-visible spectroscopy, TEM, DLS, FTIR and zeta potential analysis were applied to determine the properties of the synthesized DFX-AuNPs. The synthesized DFX-AuNPs revealed a distinct surface plasmon resonance (SPR) band at 530 nm and an average size of 16 nm as manifested by TEM analysis. In addition, Zeta potential results (−19 mV) confirmed the stability of the synthesized DFX-AuNPs. Furthermore, FTIR analysis demonstrated that DFX was adsorbed onto the surface of AuNPs via strong interaction between AuNPs and DFX. Most importantly, comparative antibacterial analysis of DFX alone and DFX-AuNPs against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) verified the superior antibacterial activity of DFX-AuNPs against the tested microorganisms. To sum up, DFX gold nano-formulations can offer a promising possible solution, even at a lower antibiotic dose, to combat pathogenic bacteria.

Gold nanoparticles have gained popularity as an effective drug delivery vehicle due to their unique features. In fact, antibiotics transported via gold nanoparticles have significantly enhanced their potency in the recent past. The present study used an approach to synthesize gold nanoparticles in one step with the help of cefoxitin antibiotic as a reducing and stabilizing agent. Cefoxitin is a second-generation cephalosporin that loses its potential due to modification in the porins (ompK35 and ompK36) of Gram-negative pathogens. Thus, the present study has developed an idea to revive the potential of cefoxitin against clinical Gram-negative pathogens, i.e., Escherichia coli and Klebsiella pneumoniae, via applying gold nanoparticles as a delivery tool. Prior to antibacterial activity, characterization of cefoxitin–gold nanoparticles was performed via UV–visible spectrophotometry, dynamic light scattering, and electron microscopy. A characteristic UV–visible scan peak for gold nanoparticles was observed at 518 nm, ζ potential was estimated as −23.6 ± 1.6, and TEM estimated the size in the range of 2–12 nm. Moreover, cefoxitin loading efficiency on gold nanoparticles was calculated to be 71.92%. The antibacterial assay revealed that cefoxitin, after loading onto the gold nanoparticles, become potent against cefoxitin-resistant E. coli and K. pneumoniae, and their MIC₅₀ values were estimated as 1.5 μg/mL and 2.5 μg/mL, respectively. Here, gold nanoparticles effectively deliver cefoxitin to the resistant pathogens, and convert it from unresponsive to a potent antibiotic. However, to obtain some convincing conclusions on the human relevance, their fate and toxicity need to be evaluated.

Objectives: This study aimed to investigate whether chromatography using an ExoPUA column, an affinity column for phospholipid membranes, could potentially serve as an efficient, rapid, scalable, and reproducible method for purifying small extracellular vesicles (sEVs). Results: We used the ExoPUA column connected to a fast-performance liquid chromatography system. One-step chromatographic purification of sEVs from culture supernatant using the ExoPUA protocol resulted in an 82 ± 16-fold increase in purity with a yield of 38 ± 5% of sEVs. The purified sEVs contained CD9, CD63, TSG101, and miRNA (miR-21), but not the endoplasmic reticulum protein Calnexin. Transmission electron microscopy indicated that the purified sEVs were intact. The purification performance of the ExoPUA protocol showed superior results in terms of yield compared to that of the differential ultracentrifugation method, the most commonly used method for purifying sEVs in laboratories, and purity compared to that of the DEAE chromatography protocol. Conclusion: The sEVs were effectively purified in the bind-elute mode and the ExoPUA column can be refreshed and sterilized with sodium hydroxide (NaOH), having high potential for multiple sEV purification in a scalable and industrial manner.

Genetic variables have a notable and polygenic impact on the incidence and development of hepatic fibrosis and cirrhosis in individuals with chronic hepatitis C (CHC). Genetic polymorphisms in interferon-λ3-interferon- λ4 (INFL3-INFL4) region, rs12979860 and its highly linked disequilibrium polymorphisms (rs368234815 and rs4803217) are linked to liver inflammation and fibrosis progression in CHC individuals from different ethnic groups. For Egyptian patients, no data available about the degree of linkage disequilibrium between these variants and their effect on liver fibrosis. In this study, 99 healthy controls and 176 CHC patients were genotyped for 3 variants in (INFL3-INFL4) region rs12979860, rs4803217, and rs368234815. We found that these variants are highly linked disequilibrium in Egyptian CHC cohort. Moreover, we found that the major alleles of these 3 polymorphisms (rs12979860, rs4803217, and rs368234815) significantly increase the risk of liver fibrosis (P = 0.015, 0.026, and 0.007 respectively). Additionally, these variants were linked to stage of hepatic fibrosis. This report shows that the 3 linked disequilibrium variants in INFL3-INFL4 region may be valuable foretellers of liver fibrosis and cirrhosis in CHC Egyptian patients.

Thrombocytopenia in chronic hepatitis C patients is a serious complication, which hinders starting and continuation of several invasive diagnoses and treatment protocols. This problem is multifactorial; therefore, it is important to explore host factors linked to it. Interestingly while we were investigating the association between rs58542926 polymorphism in TM6SF2 gene and both hepatic & extra hepatic changes, we found a significant association between TM6SF2 risk allele and thrombocytopenia in Egyptian CHC patients. There are 351 participants in this study. We measured gene expression of IL-6 and TNF-α in PBMCs and plasma thrombopoietin level in 20 CHC patients with advanced fibrosis. The minor allele was linked to elevated thrombocytopenia, and lower thrombopoietin levels. These findings raise concerns regarding the effect of this polymorphism on different diagnostic techniques and the outcomes of HCV treatment. In conclusion, we demonstrated for the first time that the occurrence of the minor allele of the rs58542926 polymorphism is associated not only with hepatic but also with extrahepatic (thrombocytopenia) alterations in CHC Egyptian patients, allowing for the use of this variant as a pharmacogenetic marker to recognize CHC patients who have a high possibility for developing late stages of liver fibrosis and extrahepatic complications.