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The study examined the possibility of intercalation of montmorillonite with neomycin in an aqueous drug solution and the factors influencing the effectiveness of this process, such as the ion exchange capacity and process conditions, including the time and temperature of incubation with the drug. X-ray diffractometry (XRD), infrared spectroscopy (FTIR), thermal analysis (DSC/TG), and Zeta potential measurement were used to confirm drug intercalation as well as to investigate the nature of clay–drug interactions. The obtained conjugates with the most favorable physicochemical properties were also tested for antibacterial response against Gram-negative bacteria (Escherichia coli) to confirm that the bactericidal properties of neomycin were retained after intercalation and UV–VIS spectrophotometry was used to examine the kinetics of drug release from the carrier. The results of the conducted research clearly indicate the successful intercalation of neomycin in montmorillonite and indicate the influence of process parameters on the properties of not only the conjugates themselves but also the properties of the intercalated drug, particularly its bactericidal activity. Ultimately, a temperature of 50 °C was found to be optimal for effective drug intercalation and the conjugates obtained within 2 h showed the highest antibacterial activity, indicating the highest potential of the thus-obtained montmorillonite conjugates as neomycin carriers. [ABSTRACT FROM AUTHOR]

Cisplatin is a chemotherapeutic agent widely used to treat solid tumors. However, it can also be highly ototoxic, resulting in high-frequency hearing loss. Cisplatin causes degeneration of hair cells (HCs) and spiral ganglion neurons (SGNs) in the inner ear, which are essential components of the hearing process and cannot be regenerated in mammals. As the affected cells primarily die by apoptosis, we tested several anti-apoptotic small molecules to protect these cells from drug-induced toxicity. We found that the general caspase inhibitor Emricasan could significantly counteract the toxic effects of cisplatin in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, phoenix auditory cells, and primary SGNs. Importantly, the anti-cytotoxic effect in neuronal cells was even more pronounced than the effect of sodium thiosulfate (STS), which is currently the only approved prevention option for cisplatin-induced ototoxicity. Finally, we tested the protective effect of Emricasan treatment in the context of another ototoxic drug, i.e., the aminoglycoside antibiotic neomycin, and again found a significant increase in cell viability when the cultures were co-treated with Emricasan. These results suggest a promising strategy to prevent ototoxicity in patients by temporarily blocking the apoptotic pathway when applying cisplatin or aminoglycoside antibiotics. Key messages: Anti-apoptotic small molecules can reduce cisplatin-induced toxicity. Emricasan can effectively exert its anti-apoptotic effect on cochlear cells. Strong protection from cisplatin- and neomycin-induced cytotoxicity with Emricasan. Sodium thiosulfate and Emricasan provide similar protective effects to cisplatin-treated cells. Emricasan is more potent than sodium thiosulfate in reducing neomycin-induced cytotoxicity. [ABSTRACT FROM AUTHOR]

Epistaxis is a common problem that can affect the whole population and is the most common ENT presentation to the emergency department.1 The majority of cases are self-limiting and do not require any medical intervention, however epistaxis can be associated with morbidity and even death in very rare circumstances. If epistaxis does not resolve with first aid measures, or episodes are frequent, patients may require specialist assessment and treatment by ENT, either in the outpatient clinic or via an unscheduled (emergency) admission to the hospital. Here, we provide an overview of the management of epistaxis in the outpatient setting and during an emergency admission in both paediatric and adult patients. We highlight the key considerations in the history and management, covering the common and rare conditions that are associated with epistaxis. This article provides an update from our most recent version published in 2021 including updated resources from British Rhinology Society guidance and review of the recent literature regarding epistaxis management. [ABSTRACT FROM AUTHOR]

The newly synthesized 1,2,3-triazole-thiazole hybrids were first evaluated for their antimicrobial activity against different microbial strains. Most of it showed a marked selectivity against Gram-positive and Gram-negative bacterial strains. The MIC assay was then assessed; for S. aureus, 4a was equipotent to the reference neomycin, while 3a, 3b, and 8b were 2-fold lower. For E. coli, compounds 3a, 4a, and 8c were equipotent to neomycin, while 5a was 8-fold higher, and 8d was 2-fold higher. Most of tested compounds showed superiority to the reference drug against C. albicans; 8a and 8e showed MIC value of 16-fold higher than neomycin, while 3a was 8-fold higher. Also, 3b and 8f were 4-fold higher; 8d was 2-fold higher, while 5a was equipotent to neomycin against the same microbe. Further biofilm formation inhibition assay was conducted to the most active compounds, 5a was the most active against the three types of bacterial strains. [ABSTRACT FROM AUTHOR]

Haematococcus lacustris (Girod-Chantrans) Rostafinski (Chlorophyta) is the richest microalgal source of astaxanthin. Natural astaxanthin from H. lacustris has been widely studied and used for commercial production worldwide. In this study, we examined the effects of 11 antibiotics (dihydrostreptomycin sulphate, neomycin, chloramphenicol, penicillin, streptomycin, ampicillin, kanamycin, gentamycin, hygromycin B, tetracycline, and paromomycin) on the biomass dry weight, growth, and astaxanthin yield of H. lacustris using Jaworski's medium without a nitrogen source. Astaxanthin content in H. lacustris was improved in the presence of ampicillin (0.25 g/L, 0.5 g/L, 1 g/L), chloramphenicol (0.25 g/L), and penicillin (0.25 g/L, 0.5 g/L, 1 g/L) in comparison to the control on day 15. The greatest increase in astaxanthin content on day 15 (6.69-fold) was obtained with the addition of penicillin (0.5 g/L) in comparison to the control. Similarly, on day 15, the cell numbers were also the highest for the H. lacustris culture grown with the addition of penicillin (0.5 g/L). [ABSTRACT FROM AUTHOR]

1. Epidemiological surveillance of Salmonella spp. serves as a primary tool for maintaining the health of poultry flocks. Characterising circulating serotypes is crucial for implementing control and prevention measures. This study conducted phenotypic and molecular characterisation of S. enterica Pullorum, S. enterica Heidelberg, and S. enterica Corvalis isolated from broiler chickens during slaughtering. 2. All strains were susceptible to gentamicin, neomycin and norfloxacin. However, resistance rates exceeded 50% for ciprofloxacin and tiamulin, irrespective of the serotype. Approximately 64% of strains were classified as multidrug-resistant, with S. enterica Heidelberg strains exhibiting significantly higher overall resistance. The isolates demonstrated the ability to adhere and produce biofilm at a minimum of three temperatures, with S. enterica Pullorum capable of biofilm production at all temperatures encountered during poultry rearing. 3. Each strain possessed between two and seven different virulence-associated genes. Genetic similarity, as indicated by pulsed field gel electrophoresis, exceeded 90% for all three serotypes and strains were classified in the R5 ribotype by PCR, regardless of serotype. Sequencing revealed high similarity among all strains, with homology ranging from 99.61 to 100% and all were classified to a single cluster. 4. The results suggested a clonal relationship among the strains, indicating the possible circulation of a unique clonal group of S. enterica Pullorum in the southern region of Brazil. [ABSTRACT FROM AUTHOR]

Background: Patients with carbapenem-resistant Enterobacterales (CRE) in the gastrointestinal (GI) tract are at risk for subsequent infections and transmission, necessitating contact precautions. Neomycin has shown in vitro activity against CRE in 66–85% of isolates. This study evaluated the efficacy and safety of neomycin for CRE decolonization. Methods: In this open-label randomized controlled trial, stool/rectal swab samples from high-risk patients were collected and tested for CRE colonization in the GI tract. Patients who had CRE and met eligible criteria were divided into a neomycin group (n = 26; treated with 4.2 g/day neomycin for 5 days) and a control group (n = 26). CRE detection in stool/rectal swabs was performed on days 7 ± 2 and 14 ± 2. Results: The two groups' baseline characteristics were similar. CRE presence on day 7 ± 2 was significantly lower in the neomycin group (46.2%) than in the control group (80.8%, p = 0.01). Efficacy of neomycin (4.2 g/day for 5 days) for CRE decolonization was 42.8–53.8% by day 7. By day 14 ± 2, the CRE rate in the neomycin group had risen to align with the control group's rate (73.1% vs. 61.5%, p = 0.56). The neomycin group experienced mild, temporary, gastrointestinal side-effects. Conclusions: Neomycin effectively reduced CRE colonization on day 7 ± 2, but its impact waned by day 14 ± 2. This suggests that neomycin dosage was too low and the duration of treatment was too short for lasting CRE decolonization. [ABSTRACT FROM AUTHOR]

Background: Combined pre-operative bowel preparation with oral antibiotics (OAB) and mechanical bowel preparation (MBP) is the current recommendation for elective colorectal surgery. Few have studied racial disparities in bowel preparation and subsequent post-operative complications. Methods: This retrospective cohort study used 2015–2021 ACS-NSQIP-targeted data for elective colectomy for colon cancer. Multivariate regression evaluated predictors of post-operative outcomes: post-operative ileus, anastomotic leak, surgical site infection (SSI), operative time, and hospital length of stay (LOS). Results: 72,886 patients were evaluated with 82.1% White, 11.1% Black, and 6.8% Asian or Asian Pacific Islander (AAPI); 4.2% were Hispanic and 51.4% male. Regression accounting for age, sex, ASA classification, comorbidities, and operative approach showed Black, AAPI, and Hispanic patients were more likely to have had no bowel preparation compared to White patients receiving MBP+OAB. Compared to White patients, Black and AAPI patients had higher odds of prolonged LOS and pro-longed operative time. Black patients had higher odds of post-operative ileus. Conclusions: Racial disparities exist in both bowel preparation administration and post-operative complications despite the method of bowel preparation. This warrants exploration into discriminatory bowel preparation practices and potential differences in the efficacy of bowel preparation in specific populations due to biological or social differences, which may affect outcomes. Our study is limited by its use of a large database that lacks socioeconomic variables and patient data beyond 30 days. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Neomycin is an aminoglycoside antibiotic that may cause contact allergy. It was withdrawn as a medicine for human use in Denmark in October 2009 but is still found in some vaccines.To identify time trends in contact allergy to neomycin in the period from 2000 to 2023.A cross‐section study of patients ≥18 years consecutively patch‐tested with neomycin sulfate (20% in pet.) at Gentofte Hospital, Denmark, during the period 2000–2023 was conducted.The overall prevalence of contact allergy to neomycin was 1.4%. The prevalence was significantly lower in the period ‘2010–2023’ (1.2%) than in ‘2000–2009’ (1.8%) (p < 0.005). Contact allergy to neomycin was significantly positively associated with facial dermatitis and age >40 years, and significantly negatively associated with occupational dermatitis and hand dermatitis. No changes in sex, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, or age > 40/≤40 (the MOAHLFA‐index) were identified when comparing neomycin contact allergic‐patients in the two periods ‘2010–2023’ and ‘2001–2009’.Neomycin is a rare cause of contact allergy in Denmark with a significantly lower prevalence following its withdrawal as a medicinal product for human use in Denmark in 2009. [ABSTRACT FROM AUTHOR]

Low-velocity penetrating brain injury (LVPBI) is a class of brain injury where a foreign object violates the skull and damages the brain. Such injuries are rare and consequently understudied. As such, we report an illustrative case of a 29-year-old female with a dense, plastic spike penetrating her right orbit and into her midbrain. After assessment with a CT scan and angiography, the object was removed with careful attention to possible vascular injury. The patient had an uncomplicated post-operative course and received antibiotic and antiepileptic prophylaxis. She was discharged on post-operative day 5, experiencing only mild left-sided weakness. Common concerns regarding LVPBI include infection, post-traumatic epilepsy, and vascular injury. A review of published LVPBI cases over the past 20 years demonstrated that most cases (55.2%) are due to accidents. Of patients undergoing surgery, 43.4% underwent a craniotomy, and 22.8% underwent a craniectomy. Despite the grave nature of LVPBI, only 13.5% of the patients died. Additionally, 6.5% of patients developed an infection over their clinical course. In all, more reported cases further paint a picture of the current state of management and outcomes regarding LVPBI, paving the way for more cohesive guidelines to ensure the best possible patient outcomes. [ABSTRACT FROM AUTHOR]

Background The extensive clinical use of Fluoroquinolones (FQs) led to the development of bacterial resistance against these agents. In this work, new lipophilic FQs were designed, prepared and screened against standard and resistant bacteria. A series of novel 7-substituted anilino-8-nitroFQ acids 3 (a-e), their reduced derivatives 4 (a-e) and their triazolo 5 (a-c) were successfully prepared, identified and characterized using NMR, and MS. FQs 3-5(a-e) were then evaluated for the in vitro antibacterial activity against standard and resistant gram-positive and gram-negative strains using serial dilution method. Combination between the new FQs and different classes of antibiotics were also tested for possible synergistic effect using checkerboard technique. Results The outcomes of the new FQs showed comparable and superior activity against both the standard strains S.aureus and E.coli with remarkable activity against the standard S.aureus strain. The reduced series 4 were the most active group among all derivatives with nanogram concentrations for 4d (60 ng/mL) and 4e (15 ng/mL) against the standard gram positive strain. Our compounds revealed appreciable or comparable MIC mean values to standard against resistant gram-positive strains (MRSA) with no inhibitory activity against gram-negative strains (MDR E.coli). The hydroxyl derivatives 6 have showed the strongest MIC mean values among all compounds. Combination of these compounds with bacitracin, ampicillin and cephalexin showed synergistic effect with fractional inhibitory concentration (FIC) index between 0.185-0.375. While combinations with erythromycin, neomycin and tetracycline showed indifference effect with FIC index 2. Conclusions Evidently increasing number of hydrogen bond acceptor/donor leads to significant increase in activity presented by compounds 4e and 6e. These findings would open the floor for these novel antibacterial agents to be used alone or in combinations with conventional antibiotics for treatment of pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Aminoglycosides are crucial antibiotics facing challenges from bacterial resistance. This study addresses the importance of aminoglycoside modifying enzymes in the context of escalating resistance. Drawing upon over two decades of structural data in the Protein Data Bank, we focused on two key antibiotics, neomycin B and kanamycin A, to explore how the aminoglycoside structure is exploited by this family of enzymes. A systematic comparison across diverse enzymes and the RNA A‐site target identified common characteristics in the recognition mode, while assessing the adaptability of neomycin B and kanamycin A in various environments. [ABSTRACT FROM AUTHOR]

In 2023, Rana dybowskii exhibiting characteristic skin ulcers were found on a farm in northeastern China. Subsequently, two dominant bacteria, Aeromonas hydrophila Rd001 and Acinetobacter johnsonii Rd002, were isolated from naturally infected R. dybowskii. Experimental infection confirmed that Rd001 was the primary pathogen responsible for the disease in R. dybowskii, with a mean lethal dose (LD50) of 6.25 × 102 CFU/g. The virulence genotype of Rd001 was identified as ser+/aha+/lip+/nuc+/hlyA+/aer+/alt+/ast+/act+. Antimicrobial susceptibility testing indicated that Rd001 was sensitive to enrofloxacin, flumequine, and neomycin. MLST analysis showed that Rd001 belonged to a new sequence type of A. hydrophila, named ST2378. This study offered the first comprehensive investigation into the pathogenicity, virulence genotypes, antimicrobial resistance, and genetic traits of A. hydrophila isolated from R. dybowskii, providing a theoretical foundation for preventing and controlling A. hydrophila infections. [ABSTRACT FROM AUTHOR]

The association of amoxicillin and clavulanic acid has shown high efficacy to treat mastitis worldwide, also promoting a shorter milk disposal period compared to other antimicrobials. However, no previous investigations regarding its application to treat mastitis in Brazilian dairy cows were developed. This study evaluated the effectiveness of amoxicillin-clavulanic acid to treat Brazilian dairy cows with mastitis, comparing it with a reference protocol treatment combination of tetracycline, neomycin and bacitracin. Holstein cows (n = 468) from three different dairy herds in Brazil were assigned to two groups: combination of tetracycline, neomycin and bacitracin (n = 178; positive control group) and amoxicillin-clavulanic acid protocol (n = 290). Before the treatment, milk samples were collected and cultivated in chromogenic media. After finishing the antimicrobial treatment (intramammary), milk samples were also collected and cultivated in chromogenic media. Results from microbiological analysis obtained before and after treatment were compared to determine the healing rate. Nine different microbiological agents were identified: eight of environmental origin and one of contagious origin; being eight grampositive and one gram-negative bacteria. TThe positive control group and the treatment group showed similar healing rate (86.5% and 90.3%, respectively; P > 0.05). No differences were found between the groups for the healing rate, when the causing agent was considered. Therefore, it is possible to indicate the amoxicillin-clavulanic acid-based protocol to treat intramammary mastitis in Brazilian dairy cows, achieving great healing rates and providing a substantial reduction in milk disposal. [ABSTRACT FROM AUTHOR]

Objective: The role of selective decontamination with oral antibiotics (OABs) and mechanical bowel preparation (MBP) prior to elective colorectal surgery is still widely debated. The objective of this study was to compare the outcomes of selective decontamination with neomycin, metronidazole and MBP compared to those of decontamination with MBP alone or with no preparation. Methods: Selective decontamination with neomycin and metronidazole combined with bowel preparation was introduced prior to elective colorectal surgery as part of an enhanced recovery after surgery program at Westmead Hospital, a major Australian tertiary referral hospital, between June 2017 and January 2023. Comparisons between short-term outcomes of OAB + MBP and MBP/no preparation were made using prospectively collected data on length of stay (LOS), readmission, mortality within 30 days, anastomotic leakage (AL), surgical site infection (SSI), urinary tract infection, deep venous thrombosis and/or pulmonary embolism, pneumonia, and ileus. Follow-up was limited to hospital stays and subsequent presentations within the health district within thirty days of surgery. The Mann–Whitney U test was used to analyse continuous data, and the chi-square test was used for categorical data. Univariate and multivariate regression modelling was performed to identify risk factors associated with an increased likelihood of SSI and AL. Results: Patients with oral neomycin and metronidazole combined with bowel preparation had reduced superficial SSI (2.7% vs. 7.6%, p = 0.043) and overall complications (32.7% vs. 44.6%, p = 0.020), particularly Clavien–Dindo 1 complications (7.3% vs. 16.5%, p = 0.009). However, the differences in AL (2.7% vs. 4.5%, p = 0.369) and organ/space SSI (1.3% vs. 3.7%, p = 0.327) were not statistically significant. The median LOS (6 d vs. 6 d, p = 0.370) was not different between the groups. Conclusion: Selective decontamination with neomycin and metronidazole reduces the risk of SSIs and overall complications. There was a trend to toward a lower AL, but this difference was not statistically significant.

Abstract Background Ototoxicity is a major side effect of many broadly used aminoglycoside antibiotics (AGs) and no FDA-approved otoprotective drug is available currently. The zebrafish has recently become a valuable model to investigate AG-induced hair cell toxicity and an expanding list of otoprotective compounds that block the uptake of AGs have been identified from zebrafish-based screening; however, it remains to be established whether inhibiting intracellular cell death pathway(s) constitutes an effective strategy to protect against AG-induced ototoxicity. Results We used the zebrafish model as well as in vitro cell-based assays to investigate AG-induced cell death and found that ferroptosis is the dominant type of cell death induced by neomycin. Neomycin stimulates lipid reactive oxygen species (ROS) accumulation through mitochondrial pathway and blocking mitochondrial ferroptosis pathway effectively protects neomycin-induced cell death. We screened an alkaloid natural compound library and identified seven small compounds that protect neomycin-induced ototoxicity by targeting ferroptosis pathway: six of them are radical-trapping agents (RTAs) while the other one (ellipticine) regulates intracellular iron homeostasis, which is essential for the generation of lipid ROS to stimulate ferroptosis. Conclusions Our study demonstrates that blocking intracellular ferroptosis pathway is an alternative strategy to ameliorate neomycin-induced ototoxicity and provides multiple hit compounds for further otoprotective drug development.

AbstractA new series of 1,3,4-thiadiazole linked to sulfa-azo derivatives via hydrazono-methyl bridge were synthesized via the reaction of methyl ((E)-(sulfa-derivatives)diazenyl) benzylidene)hydrazine-1-carbodithioates 1a-e with ethyl ester and acetyl hydrazonyl halides 2a-d. The chemical structures of the newly 1,3,4-thiadiazoles 3a-t have been clarified considring their elemental and spectral analysis. Antimicrobial activity of the newly 1,3,4-thiadiazoles was determined for Staphylococcus aureus, Escherichia coli, Candida albicans, as well as Aspergillus niger using the cup agar plate diffusion method. Out of the twenty compounds, compounds 3j, 3k, 3l, and 3s with isoxazole sulfonamides were selected for MIC assay. Compound 3j was equipotent with neomycin control drug against all tested strains, while compound 3k was 4-fold higher than neomycin against S. aureus, E. coli, and C. albicans with MIC values of 9.77, 19.53, and 19.53 μg/mL, respectively. Compound 3l was equipotent with neomycin against S. aureus and C. albicans, while it was 2-fold higher than neomycin against E. coli with MIC of 39.06 μg/mL. For 3s, it was less potent than neomycin against all tested microbs with 2-fold and 4-fold less potent. Further scanning electron microscopy (SEM) investigation has been studied to reveal the disruption effect of the selected potent antimicrobial compound (3k) on the intact cells of tested microbs S. aureus, E. coli in addition to C. albicans. Results showed that 3k exhibited a noticeable effect on destroying microbial cell walls. Furthermore, molecular docking study has been done to assess the binding behavior of two most effective compounds 3k and 3l with the target crystal structure of dihydropteroate synthase (PDB: 6CLV for S. aureus) and (PDB: 5U14 for E. coli). Compound 3k was shown to be able to form stable complexes with both target enzymes of dihydropteroate synthase through hydrogen bonding and hydrophobic interactions. [ABSTRACT FROM AUTHOR]

Two distinct spherical gold nanoparticles (AuNPs) were compared for the spectrophotometric determination of neomycin in saliva. The AuNPs were produced using AuCl3 and monobasic sodium citrate (in water bath at 100 °C) under magnetic stirring (AuNPs-citrate) and using HAuCl4 and NaBH4, at room-temperature under mechanical agitation in a commercial reactor (AuNPs-H). Both AuNPs were spherical with diameters of 7.7 nm (AuNPs-H) and 26.1 nm (AuNPs-citrate) and the maximum wavelength of the localized surface plasmon resonance (LSPR) bands were at 511 nm (AuNPs-H) and 529 nm (AuNPs-citrate). Equivalent spectral extinctions were found despite the fact the large difference in concentrations of AuNPs in dispersions: 4.2 × 10−9 mol L−1 for the AuNPs-H and 8.7 × 10−11 mol L−1 for the AuNPs-citrate. Both AuNPs interacted with aminoglycosides (AMG), affecting intensity of the LSPR band as the concentration of AMG increased. The response of the AuNPs-H was more sensitive toward AMG covering the following ranges: 0.6–600 µg L−1 (gentamicin), 7.3–550 µg L−1 (neomycin) and 14–520 µg L−1 (kanamycin). AuNPs-H optical response was more robust in function of the pH with AuNPs-citrate response only observed in acid solution, favoring electrostatic interaction with AMG. Catalytic activity of AuNPs-H, in reducing the 4-phenolate ion, presented a higher rate constant (4.3 × 10−3 s−1) and was used as analytical probe to determine neomycin in saliva after solid phase extraction with a commercially available AMG imprinted polymer enabling quantification to 0.36 μg of the analyte. [ABSTRACT FROM AUTHOR]

Background: Ototoxicity is a major side effect of many broadly used aminoglycoside antibiotics (AGs) and no FDA-approved otoprotective drug is available currently. The zebrafish has recently become a valuable model to investigate AG-induced hair cell toxicity and an expanding list of otoprotective compounds that block the uptake of AGs have been identified from zebrafish-based screening; however, it remains to be established whether inhibiting intracellular cell death pathway(s) constitutes an effective strategy to protect against AG-induced ototoxicity. Results: We used the zebrafish model as well as in vitro cell-based assays to investigate AG-induced cell death and found that ferroptosis is the dominant type of cell death induced by neomycin. Neomycin stimulates lipid reactive oxygen species (ROS) accumulation through mitochondrial pathway and blocking mitochondrial ferroptosis pathway effectively protects neomycin-induced cell death. We screened an alkaloid natural compound library and identified seven small compounds that protect neomycin-induced ototoxicity by targeting ferroptosis pathway: six of them are radical-trapping agents (RTAs) while the other one (ellipticine) regulates intracellular iron homeostasis, which is essential for the generation of lipid ROS to stimulate ferroptosis. Conclusions: Our study demonstrates that blocking intracellular ferroptosis pathway is an alternative strategy to ameliorate neomycin-induced ototoxicity and provides multiple hit compounds for further otoprotective drug development. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and validate a robust reversed‐phase high‐performance liquid chromatography (RP‐HPLC) method for the simultaneous estimation of neomycin sulfate (NEO) and beclomethasone dipropionate (BECLO) in both bulk drug and pharmaceutical dosage forms. The analysis was conducted using the Box‐Behnken design. The separation of NEO and BECLO was conducted on a Phenomenex Luna C‐18 column (4.6 × 150 mm, 5 µm), employing a mobile phase comprising a mixture of methanol and trifluoroacetic acid in a ratio of 88:12% v/v. The separation was performed at a flow rate of 0.6 mL/min. NEO and BECLO were analyzed at a wavelength of 240 nm employing a photodiode array detector. The validation of the methodology followed the guidelines outlined in the International Council for Harmonization Q2 R (1). The validation process involved assessing critical parameters such as linearity, accuracy, system suitability, precision, and robustness. The results for each parameter were found to be within the acceptable range. The results indicate that the established RP‐HPLC method can effectively be employed for the routine analysis of NEO and BECLO in bulk drug and pharmaceutical dosage forms. [ABSTRACT FROM AUTHOR]

Promoter trapping is a powerful tool for discovering promoters and uses promoter trapping vectors. However, the traditional trapping vector allows expression even if it does not integrate into the host cell genome, and even if it does integrate into the genome, it is more likely to integrate in a region other than the promoter region. In this study, to overcome the shortcomings of traditional trapping vectors, we used the bicistronic 2A system to link GFP and the neomycin resistance gene. Because this vector does not contain a promoter, simultaneous production of GFP and neomycin resistance protein requires integration into the promoter region. In fact, GFP expression was observed in more than 90% of the cell clones that survived in the medium containing antibiotics, confirming that the 2A system operates. The vector insertion location was confirmed through whole genome sequence analysis, and a 1-kb promoter candidate region was selected through promoter motif analysis. In fact, a 1-kb region inserted into a promoterless luciferase expression vector showed strong promoter activity, demonstrating its utility as a tool to find promoters. In summary, we constructed a novel promoter trapping vector using the 2A system and used it to discover the promoter with strong activity. This vector will increase the efficiency of promoter trapping, providing an opportunity to easily discover new promoters in mammalian cells. [ABSTRACT FROM AUTHOR]

Introduction: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults. The aim of this study is to investigate the effects of the buforin II gene on the expression of lncRNAs PVT1, EGOT and LINC00312 in ACHN kidney cancer cells. Material & Methods: Recombinant plasmid pcDNA3.1(+) containing buforin II gene and empty plasmid pcDNA3.1(+) were introduced into E.coli strain TOP10 by heat shock method and then purified. Then both mentioned plasmids were introduced into ACHN cells by lipofection method and screening was done by neomycin antibiotic. Finally, real time RT-PCR reaction was performed in order to investigate the expression change of EGOT, PVT1 and LINC00312 lncRNAs. Results: After lipofection, the transfected cells grew in the culture medium containing neomycin antibiotic. The real time RT-PCR reaction showed that the expression of buforin II gene in ACHN kidney cancer cells caused a significant increase in the expression of lncRNAs EGOT (P=0.0033) and LINC00312 (P=0.0272) and a significant decrease in the expression of PVT1 (P=0.0278). Discussion & Conclusion: Considering that the presence of buforin II gene causes a significant change in the expression of lncRNAs EGOT, PVT1 and LINC00312, it is possible that it can activate cell pathways including apoptosis. [ABSTRACT FROM AUTHOR]

The long-term stability of antibiotics in culture media remains underexplored in scientific literature. This study evaluated the stability of eight distinct antibiotic stock solutions—amoxicillin, cefotaxime, neomycin, oxytetracycline, florfenicol, enrofloxacin, colistin, and potentiated sulfonamide—and their 10-fold dilution series in tryptone soy broth (TSB) at 37 °C, over 12 days. Samples were collected immediately after preparation and on days 1, 2, 5, 7, 9, and 12, with active substance concentrations measured using ultra-high-performance liquid chromatography (UHPLC) coupled with mass spectrometry. The results indicated that among the ultrapure water stock solutions, neomycin, florfenicol, and potentiated sulfonamide maintained stability (>95%). Within the culture medium, florfenicol showed consistent stability (100%) throughout the study, potentiated sulfonamide experienced minor degradation (>85%), and neomycin underwent significant degradation. Amoxicillin, oxytetracycline, and colistin displayed considerable degradation in both solution types but were more stable in ultrapure water solutions. The stability of cefotaxime and enrofloxacin in ultrapure water solutions and in the medium was very similar when compared; however, 3.6% of the former and 88.7% of the latter remained detectable by day 12. These findings are crucial for minimum inhibitory concentration (MIC) assessments, especially in minimum bactericidal concentration (MBC) studies, and in experiments concerning long-term evolution and co-selection. This study underscores the necessity of stability assessments in culture media to validate future experimental outcomes. [ABSTRACT FROM AUTHOR]

Background: Antibiotics are commonly used for controlling microbial growth in diseased organisms. However, antibiotic treatments during early developmental stages can have negative impacts on development and physiology that could offset the positive effects of reducing or eliminating pathogens. Similarly, antibiotics can shift the microbial community due to differential effectiveness on resistant and susceptible bacteria. Though antibiotic application does not typically result in mortality of marine invertebrates, little is known about the developmental and transcriptional effects. These sublethal effects could reduce the fitness of the host organism and lead to negative changes after removal of the antibiotics. Here, we quantify the impact of antibiotic treatment on development, gene expression, and the culturable bacterial community of a model cnidarian, Nematostella vectensis. Methods: Ampicillin, streptomycin, rifampicin, and neomycin were compared individually at two concentrations, 50 and 200 µg mL−1, and in combination at 50 µg mL−1 each, to assess their impact on N. vectensis. First, we determined the impact antibiotics have on larval development. Next Amplicon 16S rDNA gene sequencing was used to compare the culturable bacteria that persist after antibiotic treatment to determine how these treatments may differentially select against the native microbiome. Lastly, we determined how acute (3-day) and chronic (8-day) antibiotic treatments impact gene expression of adult anemones. Results: Under most exposures, the time of larval settlement extended as the concentration of antibiotics increased and had the longest delay of 3 days in the combination treatment. Culturable bacteria persisted through a majority of exposures where we identified 359 amplicon sequence variants (ASVs). The largest proportion of bacteria belonged to Gammaproteobacteria, and the most common ASVs were identified as Microbacterium and Vibrio. The acute antibiotic exposure resulted in differential expression of genes related to epigenetic mechanisms and neural processes, while constant application resulted in upregulation of chaperones and downregulation of mitochondrial genes when compared to controls. Gene Ontology analyses identified overall depletion of terms related to development and metabolism in both antibiotic treatments. Discussion: Antibiotics resulted in a significant increase to settlement time of N. vectensis larvae. Culturable bacterial species after antibiotic treatments were taxonomically diverse. Additionally, the transcriptional effects of antibiotics, and after their removal result in significant differences in gene expression that may impact the physiology of the anemone, which may include removal of bacterial signaling on anemone gene expression. Our research suggests that impacts of antibiotics beyond the reduction of bacteria may be important to consider when they are applied to aquatic invertebrates including reef building corals. [ABSTRACT FROM AUTHOR]

Respiratory virus infections in humans cause a broad- spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon- stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID- 19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS- CoV- 2). In healthy humans, intranasal application of neomycin- containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host- directed antiviral strategy for the prevention and treatment of respiratory viral infections. [ABSTRACT FROM AUTHOR]

Riboswitches are messenger RNA (mRNA) fragments binding specific small molecules to regulate gene expression. A synthetic N1 riboswitch, inserted into yeast mRNA controls the translation of a reporter gene in response to neomycin. However, its regulatory activity is sensitive to single-point RNA mutations, even those distant from the neomycin binding site. While the association paths of neomycin to N1 and its variants remain unknown, recent fluorescence kinetic experiments indicate a two-step process driven by conformational selection. This raises the question of which step is affected by mutations. To address this, we performed all-atom twodimensional replica-exchange molecular dynamics simulations for N1 and U14C, U14C+, U15A, and A17G mutants, ensuring extensive conformational sampling of both RNA and neomycin. The obtained neomycin association and binding paths, along with multidimensional free-energy profiles, revealed a two-step binding mechanism, consisting of conformational selection and induced fit. Neomycin binds to a preformed N1 conformation upon identifying a stable upper stem and U-turn motif in the riboswitch hairpin. However, the positioning of neomycin in the binding site occurs at different RNA-neomycin distances for each mutant, which may explain their different regulatory activities. The subsequent induced fit arises from the interactions of the neomycin's N3 amino group with RNA, causing the G9 backbone to rearrange. In the A17G mutant, the critical C6-A17/G17 stacking forms at a closer RNA-neomycin distance compared to N1. These findings together with estimated binding free energies coincide with experiments and elucidate why the A17G mutation decreases and U15A enhances N1 activity in response to neomycin. [ABSTRACT FROM AUTHOR]

Aims The primary objective of this study was to analyze antimicrobial resistance (AMR), with a particular focus on β-lactamase genotypes and plasmid replicon types of Shiga toxin-producing Escherichia coli (STEC) strains originating from various animal hosts. Methods and results A total of 84 STEC strains were isolated from cattle (n  = 32), sheep/goats (n  = 26), pigeons (n  = 20), and wild animals (n  = 6) between 2010 and 2018 in various regions of Iran. The Kirby-Bauer susceptibility test and multiple polymerase chain reaction (PCR) panels were employed to elucidate the correlation between AMR and plasmid replicon types in STEC isolates. The predominant replicon types were IncFIC and IncFIB in cattle (46.8%), IncFIC in sheep/goats (46.1%), IncA/C in pigeons (90%), and IncP in wild animals (50%). STEC of serogroups O113, O26, and O111 harbored the IncFIB (100%), IncI1 (80%), and IncFIC + IncA/C (100%) plasmids, respectively. A remarkable AMR association was found between ciprofloxacin (100%), neomycin (68.7%), and tetracycline (61.7%) resistance with IncFIC; amoxicillin + clavulanic acid (88.8%) and tetracycline (61.7%) with IncA/C; ciprofloxacin (100%) with IncFIB; fosfomycin (85.7%) and sulfamethoxazole + trimethoprim (80%) with IncI1. IncI1 appeared in 83.3%, 50%, and 100% of the isolates harboring bla CTX-M, bla TEM, and bla OXA β-lactamase genes, respectively. Conclusions The emergence of O26/IncI1/ bla CTX-M STEC in cattle farms poses a potential risk to public health. [ABSTRACT FROM AUTHOR]

Objective: This review assessed the effectiveness of the nurse-led children's epistaxis clinic in streamlining patient care and avoiding unnecessary general anaesthesia. Methods: A retrospective case note review was conducted of children attending the nurse-led epistaxis clinic between 2019 and 2021. Results: A total of 718 children were seen over three years. Twelve (1.7 per cent) had a known coagulopathy. Of the children, 590 (82 per cent) had visible vessels and 29 (4 per cent) had mucosal crusting. Silver nitrate cautery was attempted under topical anaesthesia in 481 children, with 463 (96 per cent) successful cauterisations. Fifteen (3 per cent) were cauterised under general anaesthesia. Of the children, 706 (99 per cent) were prescribed nasal antiseptic preparations; this was the sole treatment for 58 (8 per cent). Blood investigations were requested for eight children (1 per cent) and haematology referral for three (0.4 per cent). Conclusion: This is the largest published series of children's nosebleeds. Given the short-lived benefit from cautery, it is suggested that general anaesthesia should not be offered routinely. However, improved haematology referral criteria are required to increase underlying diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

Simple Summary: Transportation stress can lead to a decrease in immune function and induce various oxidative stresses, which affect health and productive performance. In this experiment, lambs were fed diets containing electrolytic multivitamins and neomycin. The activities of the antioxidant enzymes SOD, GSH-Px, and CAT, and the levels of MDA and T-AOC in sera, were examined. At the same time, the activities of antioxidant enzymes SOD and GSH-Px, and the levels of MDA and T-AOC in the jejunum and colon, as well as the mRNA expressions of SOD, CAT, Nrf2, HO-1, Keap1, IL-1, IL-2, IL-12, Bax, Bcl-2, and Caspase3 in the jejunum and colon, were measured. In addition, the contents of IgA, IgG, IgM, and sIgA in the jejunum and colon were examined. It was found that road transport can decrease the antioxidant capacity and contents of immunoglobulin and increase the expression levels of inflammatory factors and apoptosis in the jejunum and colon of lambs. Electrolytic multivitamins had a better effect on improving antioxidant activity, inhibiting the expression of inflammatory factors in lambs, and potentially reducing the expression levels of apoptotic factors and oxidative damage to the jejunum and colon. Transport stress can cause damage to animals. In this experiment, 60 four-month-old lambs were randomly divided into three groups: CG (basal diet), EG (basal diet + 375 mg/d/lamb electrolytic multivitamin), and NG (basal diet + 200 mg/d/lamb neomycin). The results were as follows: during road transport, in all groups, the levels of SOD, T-AOC, and GSP-Px, and mRNA expressions of CAT, SOD, Nrf2, HO-1, and Bcl-2 in the jejunum and colon decreased (p < 0.01). However, mRNA expressions of Keap1, IL-1β, IL-2, IL-12, Bax, and Caspase3 in the jejunum and colon and the level of MDA increased (p < 0.01). The concentrations of IgA, IgG, and sIgA in the jejunum and colon also decreased (p < 0.01). In the EG and NG, the levels of SOD (p < 0.05) and T-AOC (p < 0.01) increased, and the level of MDA decreased (p < 0.01). However, in the jejunum, the levels of SOD and T-AOC, the concentrations of IgA and IgG, and mRNA expression of Bcl-2 increased (p < 0.05). mRNA expressions of IL-1, IL-2, and Caspase 3 (p < 0.05), and mRNA expression of IL-12 (p < 0.01) decreased. In the colon, SOD activity and the concentration of sIgA increased (p < 0.01). The level of MDA and mRNA expressions of IL-2 and Caspase 3 also decreased (p < 0.05). In the jejunum and colon, mRNA expression of SOD (p < 0.05) and mRNA expression of Nrf2 increased (p < 0.01). mRNA expression of Keap1 (p < 0.05) and Bax (p < 0.01) decreased. In summary, road transport can cause a decrease in antioxidant activity and immunity of lambs and an increase in oxidative damage. Electrolytic multivitamins and neomycin can improve immune function and potentially reduce oxidative damage to the jejunum and colon. [ABSTRACT FROM AUTHOR]

Resistance against aminoglycosides is widespread in bacteria. This study aimed to identify genes that are important for growth of E. coli during aminoglycoside exposure, since such genes may be targeted to re-sensitize resistant E. coli to treatment. We constructed three transposon mutant libraries each containing > 230.000 mutants in E. coli MG1655 strains harboring streptomycin (aph(3″)-Ib/aph(6)-Id), gentamicin (aac(3)-IV), or neomycin (aph(3″)-Ia) resistance gene(s). Transposon Directed Insertion-site Sequencing (TraDIS), a combination of transposon mutagenesis and high-throughput sequencing, identified 56 genes which were deemed important for growth during streptomycin, 39 during gentamicin and 32 during neomycin exposure. Most of these fitness-genes were membrane-located (n = 55) and involved in either cell division, ATP-synthesis or stress response in the streptomycin and gentamicin exposed libraries, and enterobacterial common antigen biosynthesis or magnesium sensing/transport in the neomycin exposed library. For validation, eight selected fitness-genes/gene-clusters were deleted (minCDE, hflCK, clsA and cpxR associated with streptomycin and gentamicin resistance, and phoPQ, wecA, lpp and pal associated with neomycin resistance), and all mutants were shown to be growth attenuated upon exposure to the corresponding antibiotics. In summary, we identified genes that are advantageous in aminoglycoside-resistant E. coli during antibiotic stress. In addition, we increased the understanding of how aminoglycoside-resistant E. coli respond to antibiotic exposure. [ABSTRACT FROM AUTHOR]

• Quercetin has therapeutic effects on retinopathy induced by hyperglycemia. • Quercetin protects against retinopathy by regulating gut-retina axis. • Quercetin can enhance the antioxidant capacity in the retina. Hyperglycemia-related retinopathy is a disease with a high blindness rate. Recent reports indicate that many flavonol compounds have the potential to prevent the occurrence of disease in the retina by regulating the gut–retina axis. Here, we hypothesized that quercetin could alleviate the symptoms of retinopathy. To clarify the mechanism, Sprague Dawley rats were fed a high-fat diet containing quercetin for 12 weeks and injected with streptozotocin in the ninth week. Additionally, neomycin and ampicillin were used to establish a pseudo-sterile rat model. Afterward, changes in the retina were investigated by using electroretinogram and optical coherence tomography. Blood and tissue samples were collected and biochemical components were analyzed. The extent of intestinal injury was determined via hematoxylin-eosin staining. Microbial community structure was analyzed by using 16S ribosomal RNA sequencing. Finally, the expression of genes was analyzed using real-time polymerase chain reaction. The results showed that quercetin reduced the decline in electroretinography amplitude and outer nuclear layer thickness, increased the activities of antioxidant enzymes, decreased the contents of proinflammatory factors and blood glucose, enhanced the concentration of insulin, and inhibited intestinal dysbiosis and improved gut morphology. Importantly, the underexpression of nuclear factor erythroid-2 related factor 2 in the retina was reversed by quercetin. However, trend changes were no longer significant in most of the indicators after antibiotic treatment. In summary, quercetin has therapeutic effects on retinopathy by regulating the gut–retina axis and nuclear factor erythroid-2 related factor 2 pathway, and the presence of gut microbiota helps quercetin exert its effects on the retina. Quercetin has therapeutic effects on hyperglycemia-induced retinopathy. It increases antioxidant capacity of the retina, decreases the contents of pro-inflammatory factors and the concentration of blood sugar, and restores the gut microbial composition. After the use of broad-spectrum antibiotics, the protective effects of quercetin on retinopathy are no longer significant. Red arrows indicate decreased trend, green arrows indicate increased trend, and purple circles indicate no changes. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the antibacterial activity of the crude venom of Pseudocerastes persicus against some Gram-negative and Gram-positive bacteria using an antimicrobial susceptibility test. Methods: The susceptibility of Methicillin-Resistant Staphylococcus aureus (MRSA), Listeria monocytogenes, Bacillus subtilis, Salmonella typhimurium, and E. coli O157:H7 to the crude venom of Pseudocerastes persicus was investigated at a concentration of 100 pg/ml. Standard antibiotic disks were utilized as positive controls. Furthermore, the minimum inhibitory concentration (MIC) against Staphylococcus aureus and MRSA was determined through the dilution method (160-1.25 pg/ml). These MIC values were compared with those of conventional drugs such as streptomycin (25 pg), tetracycline (30 pg), and neomycin (25 pg). Results: The crude venom exhibited significant antibacterial activity against Staphylococcus aureus, MRSA, Listeria monocytogenes, and E. coli O157:H7. It displayed moderate effects on Salmonella typhimurium but showed no significant impact on Bacillus subtilis. The MIC values against these bacteria ranged from 160 to 80 pg/ml. Conclusion: The venom from Pseudocerastes persicus demonstrates antibacterial properties and shows potential therapeutic value. Further investigations involving fractionation are necessary to fully explore its therapeutic potential. [ABSTRACT FROM AUTHOR]

Simple Summary: Transport stress damages the body health and reduces the immunity of animals. Currently, drugs such as vitamins and antibiotics, etc., are used to alleviate transport stress. In this experiment, lambs were fed diets with electrolytic multivitamin and neomycin, respectively. The weight, stress hormones and immune indicators of sera were examined. At the same time, the villus height, crypt depth and the ratio of villus height to crypt depth (V/C) were measured. Furthermore, the mRNA expressions of Occludin and MUC1, and the protein expression of Occludin in the jejunal mucosa, as well as the mRNA expressions of ZO-1 and Occludin and the protein expression of Occludin in the colonic mucosa were examined. Otherwise, the mRNA expressions of TRAF6, TLR4, MyD88 and NF-kB, and the protein expressions of TLR4 and NF-kB p65, as well as the mRNA expressions of TRAF6, TLR4 and NF-kB in the colon were measured. Adding 375 mg/d/lamb electrolytic multivitamin in the basal diet from 2 d before transportation to 7 d after transportation could potentially improve the immunity and intestinal barrier function. This provides a reference for the application of anti-stress additives to alleviate transport stress of lambs. Animals experience stress when they are transported. In this experiment, sixty 4-month-old lambs were randomly divided into three groups: CG (basal diet), EG (basal diet + 375 mg/d/lamb electrolytic multivitamin) and NG (basal diet + 200 mg/d/lamb neomycin). The transportation day was recorded as the 0th day. Blood, liver, spleen, jejunum and colon were collected on the 0th, 7th and 14th day. The results were as follows: In EG and NG groups, the lamb weights (p < 0.01), IgA and IgG (p < 0.05) increased significantly. The concentrations of ACTH, E, COR, IL-1β, IL-6 and IFN-γ decreased significantly (p < 0.01). The content of colonic propionate increased significantly (p < 0.05). The villus height and V/C increased, and crypt depth decreased significantly (p < 0.01). The mRNA expressions of Occludin and MUC1, and the protein expression of Occludin in the jejunal mucosa, the mRNA expressions of ZO-1 and Occludin, and the protein expression in the colonic mucosa increased significantly (p < 0.01). The mRNA expression of TRAF6 and the protein expression of TLR4 in the jejunum decreased significantly (p < 0.05), as well as the mRNA expressions of TLR4, MyD88 and NF-kB, and the protein expression of NF-kB p65 and the mRNA expressions of TRAF6, TLR4 and NF-kB in the colon (p < 0.01). In conclusion, an electrolytic multivitamin could potentially improve the immunity and intestinal barrier function, and when it was added with 375 mg/d in the basal diet for each lamb from 2 d before transportation to 7 d after transportation, it had a better effect than neomycin. [ABSTRACT FROM AUTHOR]

Background: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment. [ABSTRACT FROM AUTHOR]