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This study aims to examine the antimicrobial and antioxidant activities of the aerial parts of Chenopodium album extracts (CAE) prepared with different solvents, and how C. album ethanol extract protects them against gentamicin‐induced nephrotoxicity. Extracts of C. album aerial parts were obtained from ethanol, water, methanol, chloroform, and hexane solvents. Thirty‐two male Wistar albino rats were used and gentamycin‐induced nephrotoxicity was utilized as a model. The water extract of C. album exhibited no antimicrobial effect, whereas the methanol one created the highest zone diameter on Bacillus cereus (26 mm). The methanol extract displayed the highest activity in DPPH and ABTS. The ethanol extract yielded the highest reducing power in the CUPRAC. The water extract had the highest reducing power in the FRAP. Concerning gentamicin‐induced renal damage, creatinine and urea levels in the blood were statistically higher in the gentamicin‐C. album group compared to the other groups (p < .05). Urea and creatinine levels of the gentamicin‐C. album group dropped significantly, indicating that the C. album was effective against renal damage. The sections from kidney tissues in the gentamicin + C. album group mostly exhibited mild glomerular congestion. Hyaline cast, cytoplasmic vacuolization, necrosis, and apoptosis were not observed. Thanks to C. album treatment, the gentamicin + C. album suffered less histopathological damage than the gentamicin group did. The results of the present study suggest that CAE can be used as a supportive treatment in people undergoing treatment for nephrotoxicity. The therapeutic effect of Chenopodium album against nephrotoxicity was determined for the first time in this study. It was observed that ethanol extract of C. album significantly decreased the levels of urea and creatinine in gentamicin‐induced kidney damage. Among the extracts of C. album prepared with different solvents, polar solvents showed better antioxidant activity. It was determined that the water extract of C. album did not have antimicrobial activity, but other extracts had a strong antimicrobial effect.

Aminoglycoside-induced hair cell (HC) loss is a major cause of hearing impairment, and the effective prevention of HC loss remains an unmet medical need. Epigenetic mechanisms have been reported to be involved in protecting cochlear cells against ototoxic drug injury, and in this study we developed new bioactive compounds that have similar chemical structures as the epigenetics-related lysine-specific demethylase 1 (LSD1) inhibitors. LSD1 inhibitors have been reported to protect cochlear cells by preventing demethylation of dimethylated histone H3K4 (H3K4me2). To determine whether these new compounds exert similar protective effects on HCs, we treated mouse cochlear explant cultures with the new compounds together with gentamycin. There was a severe loss of HCs in the organ of Corti after gentamycin exposure, while co-treatment with the new compounds significantly protected against gentamycin-induced HC loss. H3K4me2 levels in the nuclei of HCs decreased after exposure to gentamycin, but H3K4me2 levels were maintained in the presence of the new compounds. Apoptosis is also involved in the injury process, and the new compounds protected the inner ear HCs against apoptosis by reducing caspase-3 activation. Together, our findings demonstrate that our new compounds prevent gentamycin-induced HC loss by preventing the demethylation of H3K4me2 and by inhibiting apoptosis, and these results might provide the theoretical basis for novel drug development for hearing protection.

Introduction: Tularemia is a zoonotic disease that primarily affects adults and children in rural areas. Late diagnosis in children is often associated with treatment failure and accessory surgical procedures. Objective: To analyze the diagnostic and treatment options of pediatric tularemia during the last outbreak in Kosovo during years 2014 and 2015. Methodology: This retrospective study includes 36 children treated for Tularemia at pediatric department. The diagnosis was based on clinical, serological, and PCR testing. Results: Of the 230 patients treated for tularemia, 36 (16%) were children with a median age of 9.4 years old (range 2–15 years). Major clinical manifestations included fever (97%) and swelling of lymph glands (94%), and the duration of symptoms prior to hospitalization was two weeks (range 3-60 days). Leukocytosis (41%), along with an elevated erythrocyte sedimentation rate (97%) characterized the laboratory findings. Both serology and PCR were used to confirm tularemia in children in 100% of cases. Due to abscess formation, suppuration, and high prevalence of tuberculosis, surgical procedures were used as accessory therapy and for diagnosis in half of the patients (50%). Gentamycin was the first drug of choice (97%), while 3 patients experienced relapses. Since the majority of the patients (72%) used unsafe water from wells in rural regions, the outbreak was thought to be water-related. Conclusions: Every febrile child with swollen glands should be suspected of having tularemia. Gentamycin continues to be the preferred treatment for unilateral cervical glandular type. Successful therapy depends on early diagnosis and supplemental surgical procedures.

One of the most pressing challenges in biomedical applications is the growing prevalence of bacteria that are resistant to multiple antibiotics. Metal-based nanoparticles are emerging as a promising strategy to address this problem, which is the focus of the present work. Cu 0.15 Zn 0.2 Ni 0.65 Fe 2 O 4 nano-ferrite was synthesized via the co-precipitation method. The chosen cation ratio preserves the spinel phase while Ni improves magnetic response, and Zn enhances magnetic softness and site stability. For comparison, single-cation ferrites NiFe 2 O 4 , ZnFe 2 O 4 , and CuFe 2 O 4 were synthesized using the same procedure to enable a consistent evaluation of antibacterial activity. All ferrites were characterized using XRD and FTIR. Additional analyses including UV–Vis, SEM, EDX, XPS, TEM, VSM, and Atomic Absorption Spectroscopy (AAS) were performed for Cu 0.15 Zn 0.2 Ni 0.65 Fe 2 O 4 sample. XRD confirmed a cubic spinel phase for all ferrites. FTIR provided further evidence of cation redistribution of tetrahedral and octahedral sites. AAS verified the availability of Cu 2+ , Zn 2+ , and Ni 2+ ions, supporting their contribution to antibacterial activity. VSM showed soft magnetic behavior with ~ 54.3 emu/g saturation magnetization. Antibacterial tests demonstrated that Cu 0.15 Zn 0.2 Ni 0.65 Fe 2 O 4 exhibits stronger inhibitory activity against S. aureus and E. coli at both low and high concentrations. At 500 μg/mL, the inhibition zone reached ~ 20 mm for S. aureus and ~ 17 mm for E. coli , The MIC values were found to be 40 μg/mL for S. aureus and 80 μg/mL for E. coli , indicating stronger sensitivity of Gram-positive bacteria. After establishing its individual performance, comparison has been obtained with single-cation ferrites. Across all trials, Cu 0.15 Zn 0.2 Ni 0.65 Fe 2 O 4 consistently produced larger inhibition zones, showing clear superiority. The superior antibacterial activity is attributed to the synergistic incorporation of Cu 2+ , Zn 2+ , and Ni 2+ within a single spinel lattice, giving Cu 0.15 Zn 0.2 Ni 0.65 Fe 2 O 4 strong intrinsic antibacterial activity and improving performance over single-cation ferrites, confirming its novelty and potential for biomedical applications.

The biofilm-associated infections of bones are life-threatening diseases, requiring application of dedicated antibiotics in order to counteract the tissue damage and spread of microorganisms. The in vitro analyses on biofilm formation and susceptibility to antibiotics are frequently carried out using methods that do not reflect conditions at the site of infection. To evaluate the influence of nutrient accessibility on Staphylococcus aureus biofilm development in vitro, a cohesive set of analyses in three different compositional media was performed. Next, the efficacy of four antibiotics used in bone infection treatment, including gentamycin, ciprofloxacin, levofloxacin, and vancomycin, against staphylococcal biofilm, was also assessed. The results show a significant reduction in the ability of biofilm to grow in a medium containing elements occurring in the serum, which also translated into the diversified changes in the efficacy of used antibiotics, compared to the setting in which conventional media were applied. The differences indicate the need for implementation of adequate in vitro models that closely mimic the infection site. The results of the present research may be considered an essential step toward the development of in vitro analyses aiming to accurately indicate the most suitable antibiotic to be applied against biofilm-related infections of bones.

The present study was designed to study the gentamycin (GTM)-loaded stimulus-responsive chitosan nanoparticles to treat bacterial conjunctivitis. GTM-loaded chitosan nanoparticles (GTM-CHNPs) were prepared by ionotropic gelation method and further optimized by 3-factor and 3-level Box-Behnken design. Chitosan (A), sodium tripolyphosphate (B), and stirring speed (C) were selected as independent variables. Their effects were observed on particle size (PS as Y1), entrapment efficiency (EE as Y2), and loading capacity (LC as Y3). The optimized formulation showed the particle size, entrapment efficiency, and loading capacity of 135.2±3.24 nm, 60.18±1.65%, and 34.19±1.17%, respectively. The optimized gentamycin-loaded chitosan nanoparticle (GTM-CHNPopt) was further converted to the stimulus-responsive sol-gel system (using pH-sensitive carbopol 974P). GTM-CHNPopt sol-gel (NSG5) exhibited good gelling strength and sustained release (58.99±1.28% in 12h). The corneal hydration and histopathology of excised goat cornea revealed safe to the cornea. It also exhibited significant (p<0.05) higher ZOI than the marketed eye drop. The finding suggests that GTM-CHNP-based sol-gel is suitable for ocular delivery to enhance the corneal contact time and improved patient compliance.

Bone infections are a serious problem to cure, as systemic administration of antibiotics is not very effective due to poor bone vascularization. Therefore, many drug delivery systems are investigated to solve this problem. One of the potential solutions is the delivery of antibiotics from poly(L-actide-co-glycolide) (PLGA) nanoparticles suspended in the gellan gum injectable hydrogel. However, the loading capacity and release kinetics of the system based on hydrophilic drugs (e.g., gentamycin) and hydrophobic polymers (e.g., PLGA) may not always be satisfying. To solve this problem, we decided to use hydrophobized gentamycin obtained by ion-pairing with dioctyl sulfosuccinate sodium salt (AOT). Herein, we present a comparison of the PLGA nanoparticles loaded with hydrophobic or hydrophilic gentamycin and suspended in the hydrogel in terms of physicochemical properties, drug loading capacity, release profiles, cytocompatibility, and antibacterial properties. The results showed that hydrophobic gentamycin may be combined in different formulations with the hydrophilic one and is superior in terms of encapsulation efficiency, drug loading, release, and antibacterial efficacy with no negative effect on the NPs morphology or hydrogel features. However, the cytocompatibility of hydrophobic gentamycin might be lower, consequently more extensive study on its biological properties should be provided to evaluate a safe dose.

Alruwaili NK, Zafar A, Imam SS, et al. Int J Nanomedicine. 2020;15:4717-4737. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of isotonicity images in Figure 8. The corresponding author did cooperate with the investigation and images relating to the isontonicity study were provided. However, despite the authors' assistance, it was still not clear how the images came to be duplicated, and, as we cannot verify the validity of the published work, we are therefore retracting the article. The authors have been informed and do not agree with this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as \"Retracted\".

With the rapid and continuous emergence of antimicrobial resistance, bacterial infections became a significant global healthcare concern. One of the proposed strategies to combat multidrug-resistant pathogens is to use additional compounds, such as natural biologically active substances, as adjuvants for existing antibiotics. In this study, we investigated the potential of caffeine, the widely consumed alkaloid, to modulate the antibacterial effects of antibiotics commonly used in clinical practice. We used disc diffusion assay to evaluate the effects of caffeine on 40 antibiotics in two Staphylococcus aureus strains (methicillin-resistant and methicillin-sensitive). Based on the results of this step, we selected five antibiotics for which the greatest caffeine-induced improvements in antibacterial activity were observed, and further analyzed their interactions with caffeine using a checkerboard approach. Caffeine at concentrations of 250 µg/mL or higher halved the MIC values of ticarcillin, cefepime, gentamycin, azithromycin, and novobiocin for all gram-negative species investigated (Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii). At the highest caffeine concentrations tested (up to 16 mg/mL), decreases in MIC values were 8- to 16-fold. The obtained results prove that caffeine modulates the activity of structurally diverse antibiotics, with the most promising synergistic effects observed for cefepime and azithromycin toward gram-negative pathogens.