PLGA Nanoparticles Formulations Loaded With Antibiotics Induce Sustained and Controlled Antibiotics Release for Prolonged Antibacterial Action Against MRSA, and Pseudomonas aeruginosa FRD1.

The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e., 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e., ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e., methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e., PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605, MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e., 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes.

The fluoroquinolones may positively affect tendon healing after surgical repair.

OBJECTIVES: This study aimed to evaluate the biomechanical and histological effects of fluoroquinolones on surgically repaired tendon healing. MATERIALS AND METHODS: The Achilles tendons of 40 Wistar rats (mean weight: 213.5 g; range 201 to 242 g) were bilaterally surgically cut and repaired. The rats were randomly divided into four groups: the first and third groups were designated as control groups and did not receive drug therapy, whereas the second and fourth groups received 300 mg/kg ciprofloxacin for a week after the surgical procedure. The first and second groups had both tendons dissected at the end of the first week, while the third and fourth groups were dissected at the end of the third week. The left tendons were examined biomechanically, while the right tendons were examined histologically. RESULTS: Statistical analysis revealed that the mean maximum tensile forces of tendons in the first and second groups were 5.2±1.84 N (range, 2.9 to 8.5 N) and 11.1±2.65 N (range, 7.3 to 13.9 N), respectively, which was found to be statistically significant (p< 0.05). At the end of the third week, mean maximum tensile forces of the third and fourth groups were determined to be 20.7±5.0 N (range, 22.1 to 29.8 N) and 28.7±4.6 N (range, 22.1 to 36.8 N), respectively, which was also statistically significant (p< 0.05). Histologically, our results were compatible. CONCLUSION: This study demonstrated that ciprofloxacin did not exhibit the expected adverse effects on surgically repaired tendon healing in the early stages but likely contributed to healing in the short term by affecting the inflammatory phase.

Construction of carbon quantum dots/riboflavin fluorescent probe and its application in the detection of ciprofloxacin.

The research outlined a novel approach for creating a sensitive and efficient ratio fluorescent probe for ciprofloxacin (CIP) detection. The method used the biomass materials passionfruit shell and diethylenetriamine as carbon and nitrogen sources, respectively, to prepare blue fluorescent carbon quantum dots (b-CQDs) with an average size of 3.29 nm and a quantum yield of 19.6% by a hydrothermal method. The newly designed b-CQDs/riboflavin ratio fluorescent probe demonstrates a distinct advantage for CIP monitoring, exhibiting a marked increase in fluorescence intensity at 445 nm upon interaction with CIP, while maintaining a stable intensity at 510 nm. In the water system, the I445 nm/I510 nm ratio of the fluorescent probe showed a significant linear relationship with CIP at the concentrations of 0-250 µmol·L-1, and the probe boasts a low detection limit of 0.86 µmol·L-1. The outstanding selectivity, broad detection range, low detection limits, and high quantum yield of the b-CQDs highlight their significant potential in the development of advanced sensing probes for efficient detection of ciprofloxacin, offering promising insights for future sensor technology advancements.

Septicaemia due to Vibrio vulnificus: A tropical infection not to be taken lightly.

Vibrio vulnificus is a halophilic gram-negative bacillus that can cause fulminant septicaemia in immunocompromised patients. A 67-year-old man who was immunosuppressed as a result of cytotoxic chemotherapy presented with a brief history of fever, lethargy, myalgia, and reduced oral intake. He had recently travelled to the beach to consume seafood. His blood pressure was 81/47 mm Hg, necessitating fluid resuscitation followed by inotropic support and admission to the intensive care unit. His blood culture was positive for curved gram-negative bacilli. The isolate was oxidase-positive and produced an acid butt with an alkaline slant in triple sugar iron agar. Matrix-assisted laser desorption ionization-time of flight mass spectrometry conclusively identified the isolate as V. vulnificus. Intravenous ceftazidime plus ciprofloxacin were administered, and by the fifth day of admission, he was successfully transferred out to the general ward. In total, the patient completed a 14-day course of antibiotic therapy.

A comprehensive assessment of water quality in Fayoum depression, Egypt: identifying contaminants, antibiotic pollution, and adsorption treatability study for remediation.

This study aimed to assess the current water quality status across various regions within the Fayoum depression by examining water canals, drains, and potential contaminants impacting public health and the local ecosystem. Additionally, an adsorption treatability investigation was conducted on various antibiotics identified during the assessment. Fifteen sampling points were selected across the Fayoum depression, covering surface water bodies and agricultural drainage systems during both winter and summer seasons. Physico-chemical, microbiological, and antibiotic analyses were performed on collected water samples. The water quality parameters investigated included pH, electrical conductivity, total dissolved solids (TDS), total coliforms, fecal coliforms, and concentrations of antibiotics such as ciprofloxacin and tetracycline. The findings revealed significant variations in water quality parameters among different water sources, categorizing them into three types: irrigation canals, polluted canals, and drains. High contamination levels were observed in certain water canals and drains due to untreated sewage and agricultural drainage discharge. Notably, elevated TDS levels (exceeding 1200 mg/L), microbial indicators count (with total coliforms reaching up to 2.3 × 106 CFU/100 mL), and antibiotics (with concentrations of ciprofloxacin and tetracycline exceeding 4.6 µg/L) were detected. To mitigate antibiotic contamination, a Phyto-adsorption treatability study using magnetite nanoparticles prepared with Phragmites australis plant extract demonstrated promising results, achieving complete removal of high antibiotic concentrations with an adsorption capacity of up to 67 mg/g. This study provides updated insights into water quality in the Fayoum depression and proposes a novel approach for addressing antibiotic contamination, potentially safeguarding human and environmental health.

Antimicrobial Susceptibility and Genetic Epidemiology of Extended-Spectrum ß-Lactamase-Positive Enterobacterales Clinical Isolates in Central Poland.

The extended-spectrum ß-lactamases (ESßLs) are bacterial enzymes capable of hydrolyzing penicillins, cephalosporins, and aztreonam. The prevalence of ESßL is increasing among clinically significant microorganisms worldwide, drastically reducing the therapeutic management of infectious diseases. The study aimed to determine the drug susceptibility of ESßL-positive clinical isolates acquired from patients hospitalized in Lodz, central Poland, and analyze the prevalence of specific genes, determining acquired resistance in these bacteria. The samples of ESßL-positive clinical isolates were gathered in 2022 from medical microbiological laboratories in the city of Lodz, central Poland. The strains were subjected to biochemical identification and antimicrobial susceptibility testing following EUCAST guidelines. The presence of studied genes (blaCTX-M, blaSHV, blaTEM, blaPER, blaVEB) was confirmed by PCR. Over 50% of studied isolates were resistant to gentamicin, cefepime, ceftazidime and ciprofloxacin. The most common ESßL gene was blaCTX-M. In most isolates, the resistance genes occurred simultaneously. The blaPER was not detected in any of the tested strains. ESßL-producing strains are largely susceptible to the currently available antibiotics. The observation of the coexistence of different genes in most clinical isolates is alarming.

Patterns of fluoroquinolone utilization and resistance in a tertiary care hospital: a retrospective cross-sectional analysis study from a developing country.

BACKGROUND: Fluoroquinolones are the most commonly prescribed antibiotics. Because of their known tendency to drive antimicrobial resistance, their prescribing patterns need to be more restricted. This study aimed to describe the clinical practice of fluoroquinolone prescription, dose adjustments for renal impairment patients and bacterial resistance profiles, eventually providing evidence-based recommendations to optimize antibiotic prescribing practices in the local population. METHODS: This retrospective, cross-sectional study was conducted at An-Najah National University Hospital in Palestine. The data were collected from admitted patients who were given ciprofloxacin or levofloxacin from July 2021 to June 2023. Data from 692 inpatients across various hospital departments were examined (409 for levofloxacin and 283 for ciprofloxacin). Statistical analysis was performed via IBM SPSS version 23.0 to summarize the demographic, clinical, and epidemiological data. RESULTS: The sociodemographic profile revealed diverse age distributions, with 25.4% and 39% older than 50 years for ciprofloxacin and levofloxacin, respectively. Ciprofloxacin was predominantly used in the oncology department (28.2%), with surgical prophylaxis (22.6%) and febrile or afebrile neutropenia (21.1%) being the most common indications. Levofloxacin was predominantly used in the medical ward (45.7%), mainly for lower respiratory tract infection (58.8%) and prophylaxis for bone marrow transplantation (16.5%). Enterococcus and methicillin-resistant Staphylococcus aureus were the most commonly isolated pathogens, with 62.5% of the isolates demonstrating resistance to ciprofloxacin. Moreover, extended-spectrum beta-lactamase-producing Enterobacterales were the most common pathogen isolated, with 33.3% being resistant to levofloxacin. Statistical analysis revealed a significant association between the choice of antibiotic and the approach to therapy. Levofloxacin was significantly more likely than ciprofloxacin to be used as empiric therapy (p < 0.001), whereas ciprofloxacin was more likely to be used as targeted therapy (p < 0.001). CONCLUSIONS: This study investigated prescribing practices and resistance to levofloxacin and ciprofloxacin in a large hospital in a developing country. According to the bacterial resistance profiles, we conclude that there is a need for hospital departments to exercise greater restraint on the use of these antibiotics. To this end, further studies addressing the clinical efficacy of fluoroquinolones against the current treatment guidelines to evaluate their appropriateness should be carried out.

Infection Inspection: using the power of citizen science for image-based prediction of antibiotic resistance in Escherichia coli treated with ciprofloxacin.

Antibiotic resistance is an urgent global health challenge, necessitating rapid diagnostic tools to combat its threat. This study uses citizen science and image feature analysis to profile the cellular features associated with antibiotic resistance in Escherichia coli. Between February and April 2023, we conducted the Infection Inspection project, in which 5273 volunteers made 1,045,199 classifications of single-cell images from five E. coli strains, labelling them as antibiotic-sensitive or antibiotic-resistant based on their response to the antibiotic ciprofloxacin. User accuracy in image classification reached 66.8 ± 0.1%, lower than our deep learning model's performance at 75.3 ± 0.4%, but both users and the model were more accurate when classifying cells treated at a concentration greater than the strain's own minimum inhibitory concentration. We used the users' classifications to elucidate which visual features influence classification decisions, most importantly the degree of DNA compaction and heterogeneity. We paired our classification data with an image feature analysis which showed that most of the incorrect classifications happened when cellular features varied from the expected response. This understanding informs ongoing efforts to enhance the robustness of our diagnostic methodology. Infection Inspection is another demonstration of the potential for public participation in research, specifically increasing public awareness of antibiotic resistance.

Nanocellulose-alginate composite beads for improving Ciprofloxacin bioavailability.

Nanocellulose is a potential material utilized in numerous biomedical applications. However, its hydrophilic characteristic and uncontrolled encapsulated drug release hinders nanocellulose uses in oral drug administration. Thus, this work developed novel nanocellulose/alginate composite (CNC/Alg) beads for oral delivery and bioavailability enhancement of a model drug, Ciprofloxacin (CIP). CNC was green synthesized employing electrolysis process from sugarcane bagasse. CNC/Alg beads were formulated by dropwise adding CNC-Alg mixture in CaCl2 solution at room temperature. CIP was incorporated into CNC/Alg beads by adsorption technique. X-ray diffractometry and Fourier-transform infrared spectra images showed that the beads were effectively produced with high crystallinity of 75.5 %, and the typical bond of cellulose and alginate. Within 4 h of adsorption, CIP loading efficiency reached 45.27 %, with 87.2 % molecules in the zwitterionic state. The adsorption followed Elovich and pseudo-second-order models, indicating a multi-mechanism including both physical and chemical adsorptions. Importantly, in gastrointestinal tract, the beads could protect CIP from acidic stomach environment while releasing it sustainably in simulated intestinal condition (75.05 %). The beads also showed strong antibacterial activity against both Gram(-) and Gram(+) bacteria, as evidenced by low IC50 and minimum inhibitory concentration values. Finally, CNC/Alg beads could improve CIP bioavailability for effective oral drug delivery route.

Detection of ciprofloxacin and pH by carbon dots and rapid, visual sensing analysis.

Food safety is a serious issue worldwide and practical detection method is vital for the supervision of food safety. It is necessary to establish efficient and economical methods to detect antibiotics, especially antibiotics in complex systems. This study employs citric acid and m-phenylenediamine to synthesize N, P-codoped carbon dots (N, P-CDs) by a microwave-assisted method. Anhydrous ethanol and phosphoric acid are essential to the properties of N, P-CDs. A "turn-on" fluorescent probe based on N, P-CDs was established for detecting ciprofloxacin (CIP) with detection limit down to 24.2 nm. Semiquantitative test stripe and a PS color detection system for CIP were developed to achieve visual and smart detection. The test stripe is applied to the visual detection of CIP residues in milk and a popular Chinese cuisine, Malatang, for the first time. N, P-CDs can also be used to detect pH in the range of pH 7.5-12.

Ciprofloxacin Accelerates Angiotensin-II-Induced Vascular Smooth Muscle Cells Senescence Through Modulating AMPK/ROS pathway in Aortic Aneurysm and Dissection.

Aortic aneurysm and dissection (AAD) is a cardiovascular disease that poses a severe threat to life and has high morbidity and mortality rates. Clinical and animal-based studies have irrefutably shown that fluoroquinolones, a commonly prescribed antibiotic for treating infections, significantly increase the risk of AAD. Despite this, the precise mechanism by which fluoroquinolones cause AAD remains unclear. Therefore, this study aims to investigate the molecular mechanism and role of Ciprofloxacin definitively-a type of fluoroquinolone antibiotic-in the progression of AAD. Aortic transcriptome data were collected from GEO datasets to detect the genes and pathways expressed differently between healthy donors and AAD patients. Human primary Vascular Smooth Muscle Cells (VSMCs) were isolated from the aorta. After 72 h of exposure to 110ug/ml Ciprofloxacin or 100 nmol/L AngII, either or combined, the senescent cells were identified through SA-ß-gal staining. MitoTracker staining was used to examine the morphology of mitochondria in each group. Cellular Reactive Oxygen Species (ROS) levels were measured using MitoSox and DCFH-DA staining. Western blot assay was performed to detect the protein expression level. We conducted an analysis of transcriptome data from both healthy donors and patients with AAD and found that there were significant changes in cellular senescence-related signaling pathways in the latter group. We then isolated and identified human primary VSMCs from healthy donors (control-VSMCs) and patients' (AAD-VSMCs) aortic tissue, respectively. We found that VSMCs from patients exhibited senescent phenotype as compared to control-VSMCs. The higher levels of p21 and p16 and elevated SA-ß-gal activity demonstrated this. We also found that pretreatment with Ciprofloxacin promoted angiotensin-II-induced cellular senescence in control-VSMCs. This was evidenced by increased SA-ß-gal activity, decreased cell proliferation, and elevation of p21 and p16 protein levels. Additionally, we found that Angiotensin-II (AngII) induced VSMC senescence by promoting ROS generation. We used DCFH-DA and mitoSOX staining to identify that Ciprofloxacin and AngII pretreatment further elevated ROS levels than the vehicle or alone group. Furthermore, JC-1 staining showed that mitochondrial membrane potential significantly declined in the Ciprofloxacin and AngII combination group compared to others. Compared to the other three groups, pretreatment of Ciprofloxacin plus AngII could further induce mitochondrial fission, demonstrated by mitoTracker staining and western blotting assay. Mechanistically, we found that Ciprofloxacin impaired the balance of mitochondrial fission and fusion dynamics in VSMCs by suppressing the phosphorylation of AMPK signaling. This caused mitochondrial dysfunction and ROS generation, thereby elevating AngII-induced cellular senescence. However, treatment with the AMPK activator partially alleviated those effects. Our data indicate that Ciprofloxacin may accelerate AngII-induced VSMC senescence through modulating AMPK/ROS signaling and, subsequently, hasten the progression of AAD.

Disposable electrochemical sensors based on reduced graphene oxide/polyaniline/poly(alizarin red S)-modified integrated carbon electrodes for the detection of ciprofloxacin in milk.

An electrochemical sensor based on an electroactive nanocomposite was designed for the first time consisting of electrochemically reduced graphene oxide (ERGO), polyaniline (PANI), and poly(alizarin red S) (PARS) for ciprofloxacin (CIPF) detection. The ERGO/PANI/PARS-modified screen-printed carbon electrode (SPCE) was constructed through a three-step electrochemical protocol and characterized using FTIR, UV-visible spectroscopy, FESEM, CV, LSV, and EIS. The new electrochemical CIPF sensor demonstrated a low detection limit of 0.0021 µM, a broad linear range of 0.01 to 69.8 µM, a high sensitivity of 5.09 µA/µM/cm2, and reasonable selectivity and reproducibility. Moreover, the ERGO/PANI/PARS/SPCE was successfully utilized to determine CIPF in milk with good recoveries and relative standard deviation (< 5%), which were close to those with HPLC analysis.

Measuring single-cell susceptibility to antibiotics within monoclonal bacterial populations.

The emergence of new resistant bacterial strains is a worldwide challenge. A resistant bacterial population can emerge from a single cell that acquires resistance or persistence. Hence, new ways of tackling the mechanism of antibiotic response, such as single cell studies are required. It is necessary to see what happens at the single cell level, in order to understand what happens at the population level. To date, linking the heterogeneity of single-cell susceptibility to the population-scale response to antibiotics remains challenging due to the trade-offs between the resolution and the field of view. Here we present a platform that measures the ability of individual E. coli cells to form small colonies at different ciprofloxacin concentrations, by using anchored microfluidic drops and an image and data analysis pipelines. The microfluidic results are benchmarked against classical microbiology measurements of antibiotic susceptibility, showing an agreement between the pooled microfluidic chip and replated bulk measurements. Further, the experimental likelihood of a single cell to form a colony is used to provide a probabilistic antibiotic susceptibility curve. In addition to the probabilistic viewpoint, the microfluidic format enables the characterization of morphological features over time for a large number of individual cells. This pipeline can be used to compare the response of different bacterial strains to antibiotics with different action mechanisms.

Formulations of poly(vinyl alcohol) functionalized silk fibroin nanoparticles for the oral delivery of zwitterionic ciprofloxacin.

Fibroin nanoparticles (FNP) have been employed in numerous biomedical applications. However, limited research has focused on the oral delivery of FNP and in-depth molecular interactions between the encapsulated drug and FNP. Therefore, this work developed the FNP, functionalized with poly(vinyl alcohol) (PVA), to orally deliver the zwitterionic ciprofloxacin, focused on the molecular interactions. The particles were formulated using both desolvation (the drug precipitated during the particles formulation) and adsorption (the drug adsorbed on the particles surfaces) methods. The optimal formula possessed a size of ~630 nm with narrow size distribution (measured by DLS method), spherical shape (determined by SEM), and moderate drug loading (confirmed by FT-IR, XRD, and DSC techniques) of ~50% for the desolvation method and ~43% for the adsorption method. More than 80% of the drug molecules resided on the particle surfaces, mainly via electrostatic forces with fibroin. The drug was physically adsorbed onto FNP, which followed Langmuir model and pseudo second-order kinetics. In the in-vitro simulated gastric condition at pH 1.2, the ciprofloxacin bound strongly with FNP via electrostatic forces, thus hindering the drug release (< 40%). Contrastingly, in the simulated intestinal condition at pH 6.8, the particles could control the drug release rates dependent on the PVA amount, with up to ~100% drug release. Lastly, the particles possessed adequate antibacterial activities on Bacillus subtilis, Escherichia coli, and Salmonella enterica, with MIC of 128, 8, and 32 µg/mL, respectively. In summary, the FNP and PVA functionalized FNP could be a potential oral delivery system for zwitterionic drugs.

An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial-an update to the published protocol.

This article reports an update to the protocol of the IMASOY trial, which was prospectively registered on clinicaltrials.gov (NCT04110340) in October 2019.

Dynamic responses of Salmonella Typhimurium to re-exposure to sublethal ciprofloxacin.

This study was designed to evaluate the history-dependent behaviors of Salmonella Typhimurium re-exposed to sublethal levels of ciprofloxacin. The S. Typhimurium cells were pre-exposed to 0 (CON), 1/16 (LOW), 1/8 (MED), and 1/4 (HIGH) minimum inhibitory concentrations (MICs) of ciprofloxacin, followed by re-exposure to the same concentrations. The bacterial growth, postantibiotic effect (PAE), relative fitness, and swimming motility of treatments were evaluated in the absence of ciprofloxacin. The lag phase duration (LPD) was estimate to assess bacterial recovery under ciprofloxacin exposure. A disk diffusion assay was used to determine the cross-resistance and collateral sensitivity of CON, LOW, MED, and HIGH treatments to ciprofloxacin (CIP), ceftriaxone (CEF), erythromycin (ERY), gentamicin (GEN), and polymyxin B (POL). The S. Typhimurium cells pre-exposed to ciprofloxacin were susceptible in antibiotic-free media, showing delayed growth. The highest PAE (>1 h) and bacterial fluctuation (CV = 5%) were observed at the High treatment compared to the CON. The HIGH treatment had the lowest relative fitness levels (0.87) and swimming motility (55 mm). The LPD was significantly decreased at the LOW treatment (1.8 h) when re-exposed to 1/16 × MIC of ciprofloxacin. The LOW, MED, and HIGH treatments showed the cross-resistance to POL and the collateral sensitivity to CEF, ERY, and GEN. The pre-exposure to ciprofloxacin could induce phenotypic diversity, corresponding to the history-dependent behaviors. These results provide important insights for the dynamic nature of bacterial populations when re-exposed to sublethal concentrations of antibiotics.

Tailoring zirconia surface topography via femtosecond laser-induced nanoscale features: effects on osteoblast cells and antibacterial properties.

The performance and long-term durability of dental implants hinge on the quality of bone integration and their resistance to bacteria. This research aims to introduce a surface modification strategy for zirconia implants utilizing femtosecond laser ablation techniques, exploring their impact on osteoblast cell behavior and bacterial performance, as well as the integral factors influencing the soft tissue quality surrounding dental implants. Ultrafast lasers were employed to craft nanoscale groove geometries on zirconia surfaces, with thorough analyses conducted using x-ray diffraction, scanning electron microscopy, atomic force microscopy, and water contact angle measurements. The study evaluated the response of human fetal osteoblastic cell lines to textured zirconia ceramics by assessing alkaline phosphatase activity, collagen I, and interleukin 1ßsecretion over a 7 day period. Additionally, the antibacterial behavior of the textured surfaces was investigated usingFusobacterium nucleatum, a common culprit in infections associated with dental implants. Ciprofloxacin (CIP), a widely used antibacterial antibiotic, was loaded onto zirconia ceramic surfaces. The results of this study unveiled a substantial reduction in bacterial adhesion on textured zirconia surfaces. The fine biocompatibility of these surfaces was confirmed through the MTT assay and observations of cell morphology. Moreover, the human fetal osteoblastic cell line exhibited extensive spreading and secreted elevated levels of collagen I and interleukin 1ßin the modified samples. Drug release evaluations demonstrated sustained CIP release through a diffusion mechanism, showcasing excellent antibacterial activity against pathogenic bacteria, includingStreptococcus mutans, Pseudomonas aeruginosa, andEscherichia coli.

Synthesis and characterisation of antimicrobial metal-organic frameworks as multi-drug carriers.

Antibiotic resistance is a significant global concern, necessitating the development of either new antibiotics or advanced delivery methods. With this in mind, we report on the synthesis and characterisation of a new family of Metal-Organic Frameworks (MOFs), OnG6 MOFs, designed to act as multi-drug carriers for bacterial infection treatment. OnG6 is based on the pro-drug 4,4'-azodisalicylic acid (AZDH4), which in vivo produces two equivalents of para-aminosalicylic acid (ASA), a crucial drug for M. tuberculosis treatment. X-ray and computational studies revealed that OnG6 MOFs are mesoporous MOFs with etb topology and an [M2(AZD)] formula (M = Zn, OnG6-Zn; Mg, OnG6-Mg; Cu, OnG6-Cu; and Co, OnG6-Co), featuring 1-dimensional channel type pores of 25 Å diameter. OnG6 MOFs are the first reported MOFs bearing the ligand AZDH4, joining the family of mesoporous MOFs arranged in a honeycomb pattern. They absorb isoniazid (INH) and ciprofloxacin (CIPRO) with the former being a specific antibiotic for M. tuberculosis, and the latter being a broader-spectrum antibiotic. The stability of the MOFs and their capacity for antibiotic uptake depend on the nature of the metal ion, with OnG6-Mg demonstrating the highest drug absorption. The antimicrobial activity of these species was assessed against S. aureus and E. coli, revealing that the carriers containing CIPRO displayed optimal efficacy.

A biochemical assessment of apoptosis-inducing impact of Salinomycin in combination with ciprofloxacin on human leukemia KG1-a stem-like cells in the presence and absence of insulin.

BACKGROUND: Acute Myeloid Leukemia (AML) is a fast-developing invading cancer that impacts the blood and bone marrow, marked by the rapid proliferation of abnormal white blood cells. Chemotherapeutic agents, a primary treatment for AML, encounter clinical limitations such as poor solubility and low bioavailability. Previous studies have highlighted antibiotics as effective in inducing cancer cell death and potentially preventing metastasis. Besides, insulin is known to activate the PI3K/Akt pathway, often disrupted in cancers, leading to enhanced cell survival and resistance to apoptosis. In light of the above-mentioned points, we examined the anti-cancer impact of antibiotics Ciprofloxacin (CP) and Salinomycin (SAL) and their combination on KG1-a cells in the presence and absence of insulin. METHODS: This was accomplished by exposing KG1-a cells to different doses of CP and SAL alone, in combination, and with or without insulin for 24-72 h. Cell viability was evaluated using the MTT assay. Besides, apoptotic effects were examined using Hoechst staining and Annexin-V/PI flow cytometry. The expression levels of Bax, p53, BIRC5, Akt, PTEN, and FOXO1 were analyzed through Real-Time PCR. RESULTS: CP and SAL demonstrated cytotoxic and notable pro-apoptotic impact on KG1-a cells by upregulating Bax and p53 and downregulating BIRC5, leading to G0/G1 cell cycle arrest and prevention of the PI3K-Akt signaling pathway. Our findings demonstrated that combination of CP and SAL promote apoptosis in the KG1-a cell line by down-regulating BIRC5 and Akt, as well as up-regulating Bax, p53, PTEN, and FOXO1. Additionally, the findings strongly indicated that insulin effectively mitigates apoptosis by enhancing Akt expression and reducing FOXO1 and PTEN gene expression in the cells treated with CP and SAL. CONCLUSION: Our findings showed that the combined treatment of CP and SAL exhibit a strong anti-cancer effect on leukemia KG1-a cells. Moreover, it was discovered that the PI3K-Akt signaling can be a promising target in leukemia treatment particularly in hyperinsulinemia condition.

[Occurrence and environmental risks of antibiotics in surface water of China].

Antibiotics as emerging pollutants are frequently detected in surface water, raising concerns about the associated risk of antibiotic resistance genes (ARGs). Despite the widespread apprehension, there are still research gaps in the occurrence of antibiotic pollution in surface water and the associated ecological risks to aquatic organisms in China. Here, we established a dataset of antibiotic pollution in surface water in China during 2018-2022, which encompassed 3 368 concentration values of 128 antibiotics reported in 124 articles. Our analysis showed that antibiotic concentrations were predominantly in the ng/L-µg/L range, reaching up to 26 µg/L. Notably, sulfonamides (e.g., sulfamethoxazole) and quinolones (e.g., ciprofloxacin) were frequently reported at high concentrations. The pollution degree of antibiotics represented by sulfamethoxazole, ciprofloxacin, roxithromycin, and tetracycline exhibited no significant variation across different years but was lower in summer than that in spring and autumn. Additionally, distinct spatial distribution characteristics of the pollution were observed. According to calculation results of the aquatic ecological risk assessment model and the weighted frequency, we proposed a list of priority antibiotics including clarithromycin, erythromycin, sulfamethoxazole, ofloxacin, and oxytetracycline in surface water. Last but not least, this study points out the deficiencies in current research on the occurrence and ecological risks of antibiotics in surface water of China and provides viable screening strategies and monitoring recommendations in this context.