Search Results (294)

Background: Often, neoadjuvant therapy, which relies on the induction of double-strand breaks (DSBs), is used prior to surgery to shrink tumors by inducing cancer cell apoptosis. However, recent studies have suggested that this treatment may also induce a fluctuating state between senescence and stemness in PA-1 embryonal carcinoma cells, potentially affecting therapeutic outcomes. Thus, the respective epigenetic pathways are up or downregulated over a time period of days. These fluctuations go hand in hand with changes in spatial DNA organization. Methods: By means of Single-Molecule Localization Microscopy in combination with mathematical evaluation tools for pointillist data sets, we investigated the organization of euchromatin and heterochromatin at the nanoscale on the third and fifth day after etoposide treatment. Results: Using fluorescently labeled antibodies against H3K9me3 (heterochromatin tri-methylation sites) and H3K4me3 (euchromatin tri-methylation sites), we found that the induction of DSBs led to the de-condensation of heterochromatin and compaction of euchromatin, with a peak effect on day 3 after the treatment. On day 3, we also observed the co-localization of euchromatin and heterochromatin, which have marks that usually occur in exclusive low-overlapping network-like compartments. The evaluation of the SMLM data using topological tools (persistent homology and persistent imaging) and principal component analysis, as well as the confocal microscopy analysis of H3K9me3- and H3K4me3-stained PA-1 cells, supported the findings that distinct shifts in euchromatin and heterochromatin organization took place in a subpopulation of these cells during the days after the treatment. Furthermore, by means of flow cytometry, it was shown that the rearrangements in chromatin organization coincided with the simultaneous upregulation of the stemness promotors OCT4A and SOX2 and senescence promotors p21Cip1 and p27. Conclusions: Our findings suggest potential applications to improve cancer therapy by inhibiting chromatin remodeling and preventing therapy-induced senescence. Full article

A facile method was adopted to fabricate β-C₃N₄, and it was then doped with manganese and tellurium to obtain novel 10%MnTeO₃@β-C₃N₄ (10%MnTe@β) and 20%MnTeO₃@β-C₃N₄ (20%MnTe@β) nanohybrids. The β-C₃N₄, 10%MnTe@β, and 20%MnTe@β showed surface areas of 85.86, 97.40, and 109.54 m² g⁻¹, respectively. Using ciprofloxacin (CIP) as a pollutant example, 10%MnTe@β and 20%MnTe@β attained equilibrium at 60 and 45 min with q_t values of 48.88 and 77.41 mg g⁻¹, respectively, and both performed better at pH = 6.0. The kinetic studies revealed a better agreement with the pseudo-second-order model for CIP sorption on 10%MnTe@β and 20%MnTe@β, indicating that the sorption was controlled by a liquid film mechanism, which suggests a high affinity of CIP toward 10%MnTe@β and 20%MnTe@β. The sorption equilibria outputs indicated better alignment with the Freundlich and Langmuir models for CIP removal by 10%MnTe@β and 20%MnTe@β, respectively. The thermodynamic analysis revealed that CIP removal by 10%MnTe@β and 20%MnTe@β was exothermic, which turned more spontaneous as the temperature decreased. Applying 20%MnTe@β as the best sorbent to groundwater and seawater spiked with CIP resulted in average efficiencies of 94.8% and 91.08%, respectively. The 20%MnTe@β regeneration–reusability average efficiency was 95.14% within four cycles, which might nominate 20%MnTe@β as an efficient and economically viable sorbent for remediating CIP-contaminated water. Full article

Chronic lung infection is the main predictor of morbidity and mortality in cystic fibrosis (CF), and current pharmacological alternatives are ineffective against Pseudomonas aeruginosa infections. We developed ciprofloxacin (CIP) for inhalation, aiming at improving its solubility through the formation of an amorphous solid dispersion (ASD) using gelatin (GA). CIP and GA were dissolved in varying ratios and then spray-dried, obtaining CIP-GA microspheres in a single step. The dissolution rate, size distribution, morphology, and aerodynamic properties of CIP-GA microspheres were studied, as well as their antimicrobial activity on P. aeruginosa biofilms. Microspheres formulated with a higher GA ratio increased the dissolution of CIP ten-fold at 6 h compared to gelatin-free CIP. Formulations with 75% GA or more could form ASDs and improve CIP’s dissolution rate. CIP-GA microspheres outperformed CIP in eradicating P. aeruginosa biofilm at 24 h. The spray-drying process produced CIP-GA microspheres with good aerodynamic properties, as indicated by a fine particle fraction (FPF) of 67%, a D₅₀ of 3.52 μm, and encapsulation efficiencies above 70%. Overall, this study demonstrates the potential of gelatin to enhance the solubility of poorly soluble drugs by forming ASDs. As an FDA-approved excipient for lung delivery, these findings are valuable for particle engineering and facilitating the rapid translation of technologies to the market. Full article

This research aims to establish the prevalence of imposter syndrome among Sultan Qaboos University (SQU) undergraduate students while assessing its association with depression symptoms and anxiety symptoms. A cross-sectional design recruited 504 undergraduate students selected through stratified random sampling. Data collection employed the Clance Imposter Phenomenon Scale (CIPS), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7). Data analysis included Pearson’s correlation, chi-square tests, and logistic regression analyses. In total, 56% of participants had imposter syndrome. The CIPS scores showed a moderate relationship with depression (r = 0.486, p < 0.001) and anxiety (r = 0.472, p < 0.001). Students who experienced imposter syndrome showed a higher probability of developing depressive symptoms (χ² = 45.63, p < 0.001, OR = 3.49) and anxiety symptoms (χ² = 32.96, p < 0.001, OR = 2.86). The logistic regression analysis showed that depression (B = 0.096, p < 0.001) and anxiety (B = 0.075, p = 0.003) acted as significant predictors for imposter syndrome. This study reveals a strong link between imposterism, depression, and anxiety among students. This highlights the need for university counseling programs to address imposter feelings and the role of clinical psychology in managing this phenomenon in academic and clinical settings. Full article

Background/Objectives: Optimal management of acute bacterial prostatitis (ABP) remains uncertain, but the use of antibiotics with good prostatic tissue penetration is critical to prevent recurrence and chronic progression. This study aimed to describe clinical characteristics and outcomes of ABP due to Escherichia coli (ABP-E.coli), compare effectiveness of sequential high-dose cefuroxime (ABP-CXM) versus ciprofloxacin (ABP-CIP), and identify risk factors for clinical failure. Methods: We conducted a retrospective study including men >18 years diagnosed with ABP-E. coli between January 2010 and November 2023 at a 400-bed hospital. Patients received oral cefuroxime (500 mg/8 h) or oral ciprofloxacin (500 mg/12 h). Outcomes over 90 days included clinical cure, recurrence and reinfection. Definitions: Clinical cure—resolution of symptoms without recurrences; recurrence—new ABP episode with the same E. coli strain; reinfection—ABP involving different microorganism or E. coli strain; clinical failure—lack of cure, recurrence, or reinfection. Results: Among 326 episodes (158 ABP-CXM, 168 ABP-CIP), ABP-CXM patients were younger (median 63.5 vs. 67.5 years, p = 0.005) and had fewer comorbidities. Clinical cure was higher in ABP-CIP (96.9% vs. 85.7%, p < 0.001). Recurrence occurred only in ABP-CXM (6.96% vs. 0%, p < 0.001), while reinfection and mortality were similar. Multivariable analysis showed ciprofloxacin was protective against clinical failure (OR: 0.16, 95% CI: 0.06–0.42, p < 0.001), while prior urinary tract infection (UTI) increased failure risk (OR: 2.87, 95% CI: 1.3–6.3). Conclusions: Ciprofloxacin was more effective than cefuroxime in treating ABP-E. coli. Patients with recent UTIs may need closer monitoring or alternative therapies. Full article

Background: Campylobacter causes gastroenteritis worldwide with increasing antimicrobial resistance. Furazolidone (FZD) shows potential in resource-poor areas but needs further study. We aimed to assess the in vitro susceptibility of Campylobacter spp. to FZD, ciprofloxacin (CIP), and erythromycin (ERY) in a high-risk pediatric cohort and to evaluate the clinical relevance of resistance patterns using inhibitory quotient (IQ) pharmacodynamics. Methods: A two-phase prospective study (2012–2013, 2014–2015) was conducted at a tertiary pediatric hospital in Lima, Peru. Stool samples from children ≤24 months were cultured on selective media, with Campylobacter isolates identified via conventional bacteriological methods. Antimicrobial susceptibility was determined using Kirby–Bauer disk diffusion and regression-derived minimum inhibitory concentrations (MICs). IQ analysis correlated inhibition zones with therapeutic outcomes. Results: Among 194 Campylobacter isolates (C. jejuni: 28%; C. coli: 72%), resistance to CIP declined from 97.7% (2012–2013) to 83% (2014–2015), while ERY resistance rose from 2.3% to 9.4% (p= 0.002). No FZD resistance was observed, with mean inhibition zones of 52 ± 8 mm (2012–2013) and 43 ± 10.5 mm (2014–2015). MICs for FZD were predominantly <0.125 μg/mL, and all susceptible isolates demonstrated favorable IQ outcomes. Multidrug resistance (≥2 drugs) increased to 6.2% (2014–2015), though all MDR strains retained FZD susceptibility. CLSI and EUCAST breakpoints showed concordance for ERY (p = 0.724) but discordance for CIP (p = 0.022 vs. 0.008). Conclusions: FZD exhibits sustained in vitro efficacy against Campylobacter spp., even among MDR strains, contrasting with escalating fluoroquinolone and macrolide resistance. Full article

Background: Checkpoint inhibitor-associated pneumonitis (CIP) after immunotherapy has become a challenging issue in non-small cell lung cancer (NSCLC) patients. This study leverages artificial intelligence (AI) algorithms to analyze radiomic features, aiming to predict the occurrence of CIP, as well as tumor response. Methods: This study analyzed data from 159 stage III-IV NSCLC patients undergoing immunotherapy. The patients were categorized into pneumonitis and non-pneumonitis groups, and 3D radiomic features from both tumors and surrounding regions were extracted using LIFEx software. To address scanner-associated variations, a linear mixed-effect radiomics harmonization model was applied. A random forest algorithm was then used to develop models predicting CIP occurrence and tumor responses based on the pre-treatment CT radiomics. The accuracy was evaluated using the area under the curve (AUC). Results: A total of 159 patients were analyzed, of which only 31 experienced CIP. Most had grade 1 (17/31, 54.8%) or 2 (12/31, 38.7%) pneumonitis; only two (6.5%) patients had grade 3. Patients who developed pneumonitis were more likely to be male (64.5% vs. 38.3%, p = 0.014), had less adenocarcinoma histology (54.8% vs. 78.9%, p = 0.032), and exhibited a higher tumor mutational burden (57.1% vs. 24.5%, p = 0.047). Radiomics analysis reported predictability for CIP with an AUC of 0.60 (95% CI 0.55–0.66). The five-year overall and progression-free survival rates were 24.7% (95% CI 15.2–35.5%) and 9.7% (95% CI 4.4–17.4%), respectively. The radiomics features also exhibited AUCs of 0.63 (95% CI 0.59–0.67) in irRECIST and 0.66 (95% CI 0.61–0.70) in RECIST 1.1 in terms of tumor responses to immunotherapy. Conclusions: This study provides insights into the potential role of radiomic models in predicting CIP and tumor responses from pre-treatment CT images of NSCLC patients treated with immunotherapy. Full article

Background/Objectives: Actinic keratosis (AK) occurs on sun-damaged skin and is considered a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) and red light, is a common treatment for AK. However, its clinical efficacy for invasive tumors such as SCC is limited by the poor penetration and distribution of the photosensitizer. Cold atmospheric plasma (CAP), a partially ionized gas, increases skin permeability and exhibits anti-cancer properties through the generation of reactive oxygen species (ROS). In a previous study, CAP showed promising synergistic effects when combined with ALA-PDT for the treatment of SCC cells in vitro. The present study investigated the effects of combining CAP with ALA-PDT on cutaneous AK and SCC induced by ultraviolet B (UV-B) irradiation in SKH1 hairless mice. Methods: We compared various application sequences (CAP-ALA–red light, ALA–red light–CAP, and ALA-CAP–red light) against conventional ALA-PDT using visual, histological, and molecular assessments of the affected skin. Results: The results demonstrated that combined treatments strongly inhibited the growth of UV-B-induced skin lesions. TUNEL staining revealed increased apoptosis following both single and combined therapies, while Ki-67 staining indicated reduced keratinocyte proliferation and diminished DNA damage in treated areas. mRNA expression analysis showed the upregulation of apoptosis-related genes (p16^INK4a, p21^CIP1) alongside enhanced anti-tumor immune responses (IL-6, IL-8) in the affected tissue samples. Notably, the combined treatment enhances the therapeutic effect, whereas the sequence of application does not seem to be relevant for therapeutic efficacy in vivo. Conclusions: Overall, these results suggest that CAP may enhance the anti-tumor effect of conventional ALA-PDT, supporting previous findings on SCC cells. Full article

The presence of fluoroquinolone (FQ) residues in food-producing animals has raised concerns regarding antimicrobial resistance. This study evaluated the occurrence of FQ residues in the liver and kidneys of piglets and their association with resistance patterns in Escherichia coli and Enterococcus species from piglets’ intestinal microbiota. FQ residues were found in 44% of livers and 23% of kidneys. Among 340 E. coli isolates from feces, resistance to ciprofloxacin (CIP) (43.2%) and multidrug resistance (MDR) (82.7%) were prominent. The presence of FQ in kidneys significantly increased the odds of CIP-resistant E. coli (OR = 2.94, p = 0.0013) and MDR (OR = 2.70, p = 0.0047). Enterococci (n = 130) were evenly distributed among the species E. faecalis, E. faecium, and Enterococcus spp. and presented resistance to CIP (34.6%). FQ in kidneys were associated with higher odds of CIP-resistant enterococci (OR = 3.78, p = 0.015). Interaction models revealed species-dependent responses, with Enterococcus spp. showing high resistance in the presence of FQ in kidneys (OR = 18, p = 0.006), while E. faecium exhibited lower resistance compared to E. faecalis. These findings emphasize the role of FQ residues in promoting bacterial resistance and underscore the need for the stricter regulation and routine surveillance of antimicrobial use in livestock to curb the spread of bacterial resistance to clinical drugs, and mitigate public health risks—One Health. Full article

Older age is a risk factor for glaucoma, in which progressive retinal ganglion cell (RGC) loss leads to visual field defects and irreversible visual impairment and even blindness. We recently identified the involvement of cellular senescence in RGC cell death post-optic nerve injury. Here we further aimed to delineate the profile of RGC survival in mice with aging, a physiological process with increasing cellular senescence. The numbers of senescent cells in the ganglion cell layer (GCL) significantly and progressively increased starting at 8 months of age. Yet, significant reduction of ganglion cell complex layer thickness began in the 10-month-old mice, and significant reduction in the number of RGCs began in the 12-month-old mice as compared to the 2-month-old mice. Meanwhile, pyroptosis and ferroptosis markers as well as cellular senescence-related cell cycle arrest proteins p15^Ink4b, p16^Ink4a, p21^Cip1, and p53 were significantly and progressively increased in GCL. In contrast, there were no significant changes in dendritic field, complexity, and branches with increasing ages. Comparing between the 2- and 16-month-old mouse retinas, the differentially expressed genes were involved in the pathways of neurodegeneration, innate immunity, and mitochondrial ATP synthesis. In summary, this study revealed the gradual increase in senescent cells as well as pyroptosis and ferroptosis with progressive RGC reduction in mice with aging. Cellular senescence and the related cell death pathways are potential targets for age-related RGC reduction. Full article

To investigate the effects and underlying mechanisms of the Chinese herbal medicine berberine hydrochloride (BBH) on the pharmacokinetics of the antibiotic ciprofloxacin hydrochloride (CIP) in yellow catfish (Pelteobagrus fulvidraco), this study established two experimental groups: CIP alone and CIP combined with BBH. After administering the two treatment groups, we analyzed the pharmacokinetic characteristics and tissue distribution of CIP in yellow catfish, as well as the differences in the expression levels of two key genes involved in drug disposition—ABCB4 (ATP-binding cassette subfamily B member 4, related to drug transport) and CYP3A40 (cytochrome P450 3A40, related to drug metabolism)—in the intestinal tract. The results demonstrated that co-administration of CIP and BBH increased the maximum concentration (C_max) and area under the concentration–time curve (AUC) of CIP while reducing its total body clearance (CL/F). Regarding gene expression, the combined treatment significantly downregulated ABCB4 expression in the intestine at certain time points compared to CIP alone, whereas CYP3A40 expression showed a non-significant decreasing trend. These findings suggest that BBH may enhance the absorption of CIP in yellow catfish by suppressing ABCB4 expression, thereby improving therapeutic efficacy at the same dosage. Full article

Soil heavy metal contamination poses critical challenges to ecological sustainability in mining regions, particularly in acidic soils from copper sulfide mines. This study developed a sustainable remediation strategy using a carbonyl iron powder–biochar composite (CIP@BC) derived from agricultural waste (rice husk) and industrial byproducts. The composite was synthesized through an energy-efficient mechanical grinding method at a 10:1 mass ratio of biochar to carbonyl iron powder, aligning with circular economy principles. Material characterization revealed CIP particles uniformly embedded within biochar’s porous structure, synergistically enhancing surface functionality and redox activity. CIP@BC demonstrated exceptional Cu²⁺ immobilization capacity (910.5 mg·g⁻¹), achieved through chemisorption and monolayer adsorption mechanisms. Notably, the remediation process concurrently improved key soil health parameters. Soil incubation trials demonstrated that 6% CIP@BC application elevated soil pH from 4.27 to 6.19, reduced total Cu content by 29.43%, and decreased DTPA-extractable Cu by 67.26%. This treatment effectively transformed Cu speciation from bioavailable to residual fractions. Concurrent improvements in electrical conductivity (EC), cation exchange capacity (CEC), soil organic matter (OM), and soil water content (SWC) collectively highlighted the composite’s multifunctional remediation potential. This study bridges environmental remediation with sustainable land management through an innovative waste-to-resource approach that remediates acidic mine soils. The dual functionality of CIP@BC in contaminant immobilization and soil quality restoration provides a scalable solution. Full article

Objective: Immune checkpoint inhibitors (ICIs) are front-line treatment options for NSCLC. ICI therapy is associated with a risk of immune-related adverse events (irAEs). Checkpoint inhibitor pneumonitis (CIP) is a potentially life-threatening irAE. Previous studies have demonstrated that asthma and interstitial lung disease are associated with an increased risk of CIP. We sought to determine whether chronic obstructive pulmonary disease (COPD) is associated with CIP. Methods: This retrospective study examines a cohort of ICI-treated NSCLC patients either with or without chemotherapy at the Anna and Peter Brojde Lung Cancer Centre, Jewish General Hospital in Montreal, Canada between 2014 and 2023. We explored associations between risk factors and CIP using the Mann–Whitney U test or Fisher’s exact test. Analysis of prognostic factors was performed using a logistic regression model. All statistical analyses were carried out using SPSS software, version 24.0 (SPSS, Chicago, IL, USA). p-values of 0.05 or less were considered significant. Results: Of the 327 selected patients on ICIs, 23 experienced an acute respiratory deterioration that was attributed to CIP, 87/327(26.6%) patients had a pre-existing diagnosis of COPD, and 11/87 (12.6%) COPD patients experienced CIP compared to 13/240 (5.5%) non-COPD patients (p = 0.061). There was no statistical or clinically meaningful correlation between COPD severity and CIP. The only variable significantly associated with CIP was a poor ECOG performance status. Among ECOG 1 patients, 18/91 (19.8%) experienced CIP compared to 5/226 (2.2%) of those with an ECOG of 0. A multivariate assessment involving all 327 patients revealed no significant factors affecting CIP development. Conclusions: Our single-institution study revealed that although there was a trend, the presence of COPD was not statistically associated with an increased risk of CIP. Additionally, neither FEV1 nor DLCO had a meaningful impact on the development of CIP in COPD patients. Given these findings, we emphasize the need for larger prospective studies to confirm these observations before drawing definitive clinical recommendations. Full article

In this study, an effective composite material, manganese-modified magnetic dual-sludge biochar (Mn@MDSBC), was developed for the adsorption of ciprofloxacin hydrochloride (CIP). This composite was prepared by means of a simple one-pot method, which involved the pyrolysis of iron-based waterworks sludge (IBWS) and paper mill sludge (PMS) loaded with manganese (Mn) under controlled conditions in a nitrogen atmosphere. The synthesized Mn@MDSBC was subjected to a comprehensive suite of characterization approaches, which included N₂ adsorption–desorption, X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Subsequently, static adsorption tests were conducted to investigate how different factors, including the initial solution pH, reaction time and temperature, CIP concentration, and ionic strength influence the adsorption of CIP by Mn@MDSBC. Mn@MDSBC had the maximum CIP adsorption capacity of 75.86 mg/g at pH 5, among the pH values ranging from 3 to 9. The pseudo-second order model provided the best description of the adsorption process, while the experimental data aligned more closely with the Langmuir equation than with the Freundlich model, indicating monolayer adsorption. The adsorption process was found to be non-spontaneous and exothermic according to thermodynamic analysis. The presence of Cl⁻ and SO₄²⁻ enhanced CIP adsorption, while PO₄³⁻ weakened it. After five cycles of reuse, Mn@MDSBC experienced a 17.17% loss in CIP adsorption capacity. The primary mechanisms for CIP removal by Mn@MDSBC were identified as physical and chemical adsorption, hydrogen bonding, and π-π stacking interactions. In summary, the study underscores the high efficiency of Mn@MDSBC as a composite material for CIP adsorption, highlighting its potential for application in wastewater treatment processes. Full article

The co-occurrence of microplastics (MPs) and antibiotics as emerging contaminants demonstrates significant ecological perturbations in soil matrices. Of particular scientific interest is the potential for MPs to mediate the environmental fate and transport dynamics of co-existing antibiotics. This study investigated MP-mediated ciprofloxacin (CIP) adsorption in lateritic soils. Batch experiments with polyethylene (PE), polypropylene (PP), and poly (ethylene-terephthalate) (PET) revealed soil components dominated CIP retention, while 10% (w/w) MPs reduced soil adsorption capacity by ≥10.8%, with inhibition intensity following PET > PE > PP. Adsorption thermodynamics exhibited significant pH dependence, achieving maximum sorption efficiency at pH 5.0 (± 0.2), which was approximately 83%. Competitive adsorption analysis demonstrated inverse proportionality between ionic strength and CIP retention, with trivalent cations exhibiting superior competitive displacement capacity compared to mono- and divalent counterparts. Isothermal modeling revealed multilayer adsorption mechanisms governed by hybrid chemisorption/physisorption processes in both soil and MP substrates. Spectroscopic characterization suggested differential adsorption pathways: MP-CIP interactions were primarily mediated through hydrophobic partitioning and π-π electron coupling, while soil–MP composite systems exhibited dominant cation exchange capacity and surface complexation mechanisms. Notably, electrostatic attraction/repulsion forces modulated adsorption efficiency across all experimental conditions, particularly under varying pH regimes. This work advances understanding of co-contaminant dynamics in soil ecosystems, informing risk assessment frameworks. Full article