Search Results (1,475)

Antimicrobial resistance (AMR) in Campylobacter species, particularly C. jejuni and C. coli, poses a significant public health threat. These bacteria, which are commonly found in livestock, poultry, companion animals, and wildlife, are the leading causes of foodborne illnesses, often transmitted through contaminated poultry. Extensive exposure to antibiotics in human and veterinary medicine creates selection pressure, driving resistance through mechanisms such as point mutations, horizontal gene transfer, and efflux pumps. Resistance to fluoroquinolones, macrolides, and tetracyclines complicates treatment and increases the risk of severe infections. Drug-resistant Campylobacter is transmitted to humans via contaminated food, water, and direct contact with animals, highlighting its zoonotic potential. Addressing this challenge requires effective interventions. Pre-harvest strategies like biosecurity and immune-based methods reduce bacterial loads on farms, while post-harvest measures, including carcass decontamination and freezing, limit contamination. Emerging approaches, such as bacteriocins and natural antimicrobials, offer chemical-free alternatives. Integrated, multidisciplinary interventions across the food chain are essential to mitigate AMR transmission and enhance food safety. Sustainable agricultural practices, antimicrobial stewardship, and innovative solutions are critical to curbing Campylobacter resistance and protecting global public health. Our review examines the dynamics of antimicrobial resistance in Campylobacter and presents current strategies to mitigate Campylobacter-related AMR, offering valuable insights for antimicrobial control in the poultry industry. Full article

Second-generation integrase strand transfer inhibitors (INSTIs) are strongly recommended for people living with HIV-1 (PLWH). The emergence of resistance to second-generation INSTIs has been infrequent and has not yet been a major issue in high-income countries. However, the delayed rollouts of these INSTIs in low- to middle-income countries during the COVID-19 pandemic combined with increased transmission of drug-resistant mutants worldwide are leading to an increase in INSTI resistance. Herein, we evaluated the antiviral potencies of our lead developmental INSTI 4d and the second-generation INSTIs dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB) against a panel of IN quadruple mutants. The mutations are centered around G140S/Q148H, including positions L74, E92, and T97 combined with E138A/K/G140S/Q148H. All of the tested INSTIs lose potency against these IN quadruple mutants compared with the wild-type IN. In single-round infection assays, compound 4d retained higher antiviral potencies (EC₅₀ values) than second-generation INSTIs against a subset of quadruple mutants. These findings may advance understanding of mechanisms that contribute to resistance and, in so doing, facilitate development of new INSTIs with improved antiviral profiles. Full article

2-phenylchromen-4-one, commonly known as flavone, plays multifaceted roles in biological response that can be abundantly present in natural sources. The methoxy group in naturally occurring flavones promotes cytotoxic activity in various cancer cell lines by targeting protein markers, in facilitating ligand–protein binding mechanisms and activating cascading downstream signaling pathways leading to cell death. However, the lipophilic nature of these analogs is a key concern as it impacts drug membrane transfer. While lipophilicity is crucial for drug efficacy, the excessive lipophilic effects in flavonoids can reduce water solubility and hinder drug transport to target sites. Recent in vitro studies suggest that the incorporation of polar hydroxyl groups which can form hydrogen bonds and stabilize free radicals may help overcome the challenges associated with methoxy groups while maintaining their essential lipophilic properties. Naturally coexisting with methoxyflavones, this review explores the synergistic role of hydroxy and methoxy moieties through hydrogen bonding capacity in maximizing cytotoxicity against cancer cell lines. The physicochemical analysis revealed the potential intramolecular interaction and favorable electron delocalization region between both moieties to improve cytotoxicity levels. Together, the analysis provides a useful strategy for the structure–activity relationship (SAR) of flavonoid analogs in distinct protein markers, suggesting optimal functional group positioning to achieve balanced lipophilicity, effective hydrogen bonding, and simultaneously minimized steric hindrance in targeting specific cancer cell types. Full article

Heterojunction formation between BiVO₄ nanomaterials and benchmark semiconductor photocatalysts has been keenly pursued as a promising approach to improve charge transport and charge separation via interfacial electron transfer for the photoelectrocatalytic degradation of recalcitrant pharmaceutical pollutants. In this work, a heterostructured TiO₂/Mo-BiVO₄ bilayer photoanode was fabricated by the deposition of a mesoporous TiO₂ overlayer using the benchmark P25 titania catalyst on top of Mo-doped BiVO₄ inverse opal films as the supporting layer, which intrinsically absorbs visible light below 490 nm, while offering improved charge transport. A porous P25/Mo-BiVO₄ bilayer structure was produced from the densification of the inverse opal underlayer after post-thermal annealing, which was evaluated on photocurrent generation in aqueous electrolyte and the photoelectrocatalytic degradation of the refractory anti-inflammatory drug ibuprofen under back-side illumination by visible and UV–Vis light. Significantly enhanced photoelectrochemical performance on both photocurrent density and pharmaceutical degradation was achieved for the bilayer structure with respect to the additive effect of the constituent layers, which was related to the improved light harvesting arising from the backscattering by the mesoporous TiO₂ layer in combination with the favorable charge transfer at the TiO₂/Mo-BiVO₄ interface. Full article

Background: In this study, two chalcone analogs were synthesized through in silico and experimental methods, and their potential to inhibit the lipoxygenase enzyme, which plays a role in the inflammation pathway, was assessed. Specifically, this study is a continuation of previous research in which chalcone derivatives were synthesized and characterized. Objectives/Methods: In the current work, we present the re-synthesis of two chalcones, with a focus on their docking studies, NMR analysis, and dynamic simulations. The structure of each chalcone was elucidated through a combination of Nuclear Magnetic Resonance (NMR) and Density Functional Theory (DFT). The substituent effect on the absorption spectrum of the two chalcone derivatives was studied. Results: A “LOX–chalcone” complex, predicted by docking studies, was further examined using molecular dynamics (MD) simulations to evaluate the stability of the complex. After fully characterizing the “LOX–chalcone” complexes in silico, the atomic details of each chalcone’s interaction with LOX-1 and 5-LOX were revealed through Saturation Transfer Difference (STD) NMR (Nuclear Magnetic Resonance). Finally, their selectivity profile was investigated against human 15-LOX-1 and general Lipoxidase activity. Conclusions: The in silico methods suggest that chalcones could be promising lead compounds for drug designs targeting the LOX enzyme. Full article

Background/Objectives: Although Staphylococcus epidermidis is a key cause of subclinical mastitis in Danish dairy cows, its sensitivity to antimicrobials remains unexplored. Here, we analyzed sixty S. epidermidis isolates derived from 42 dairy cows across six conventional dairy herds in Denmark. Methods: Phenotypic resistance was measured by antimicrobial susceptibility testing and minimum inhibitory concentration (MIC) analysis, and genotypic resistance was examined through whole-genome sequencing and identification of antimicrobial resistance genes (ARGs). Correspondence between phenotypic and genotypic resistance was then evaluated by Cohen’s kappa statistics. Furthermore, the presence of plasmid replicon genes and the strain diversity among the S. epidermidis isolates was investigated to associate these findings with the observed AMR patterns. Results: Results showed that 30/60 isolates (50.0%) were resistant to penicillin phenotypically, while 35/60 (58.3%) were positive for a corresponding blaZ gene (κ = 0.83, p < 0.01). A fosB gene, encoding fosfomycin resistance, was detected in all 60/60 isolates (100.0%), but fosfomycin resistance was not analyzed phenotypically. Based on MIC analysis, 3/60 isolates (5.0%) were multi-drug resistant, showing resistance towards penicillin, erythromycin, and tetracycline. However, in 11/60 genomes (18.3%), ARGs encoding resistance towards ≥3 antimicrobial classes (e.g., beta-lactams, phosphonic acid, tetracyclines, aminoglycosides, macrolides, lincosamides, and fusidane) were detected. Eleven different ARGs were detected among the 60 isolates in total. No methicillin-resistant Staphylococcus epidermidis (MRSE) were recorded. Results further showed that each herd had one primary sequence type (ST) and resistance profile associated with it, and plasmid-mediated horizontal gene transfer of ARGs was indicated This study underscores the importance of routine resistance surveillance and species-specific diagnoses to improve treatment outcomes and ensure prudent use of antimicrobials. Full article

Glaesserella parasuis is the etiological agent of Glässer’s disease, which causes high morbidity and mortality in pigs worldwide. Macrolide resistance poses an urgent threat to their treatment, as macrolides are widely used for preventing and treating G. parasuis infections. Here, we determined the susceptibilities to five macrolides and characterized the genetic markers of macrolide resistance. The antimicrobial susceptibility of 117 G. parasuis isolates to erythromycin, tulathromycin, gamithromycin, tylosin, and tilmicosin was evaluated using broth microdilution method. Erythromycin-resistant isolates were sequenced using whole-genome sequencing. Further analysis of these sequences revealed the genetic basis of macrolide resistance in G. parasuis. Our results show that most G. parasuis isolates remained susceptible to the macrolide drugs. For commonly used agents (e.g., tylosin and tilmicosin), elevated minimum inhibitory concentrations (MICs) were observed, whereas for the newer macrolides (e.g., tulathromycin and gamithromycin), the MICs remained almost unchanged. The macrolide resistance gene erm(T) and the A2059G mutation in 23S rRNA were detected in the current study. To the best of our knowledge, integrative and conjugative element (ICE)-borne erm(T) in G. parasuis is reported for the first time in this study. Taken together, these results provide insights into the susceptibility of G. parasuis to macrolides. The presence of erm(T) on ICEs may facilitate its transfer, reducing the effectiveness of macrolide treatment. Full article

A novel fluorescent probe, Bibc-DNBS, based on the combination of the PET (photoinduced electron transfer) and ESIPT (excited-state intramolecular proton transfer) mechanisms, was designed and synthesized. Bibc-DNBS exhibited a Stokes shift of 172 nm in the fluorescence detection field. In addition, the probe exhibited good performance in key parameters in bioassays such as sensitivity, specificity, and response time. Based on these properties, Bibc-DNBS successfully monitored the biothiol levels in live cells and zebrafish models, providing an effective analytical tool for real-time monitoring of biothiols. More importantly, Bibc-DNBS could be useful for indirectly detecting β-lactamases. Bibc-DNBS(3-(1H-benzo[d]imidazol-2-yl)-4′-cyano-[1,1′-biphenyl]-4-yl2,4-dinitrobenzenesulfonate) facilitated the screening of β-lactamase inhibitors, using tazobactam and clavulanic acid as model compounds, with respective semi-inhibitory concentration values of 31.32 μM and 2.26 μM, respectively. It might also be applied to distinguish sensitive strain Staphylococcus aureus ATCC 29213 and drug-resistant strain Enterobacter cloacae ATCC 13047, which could provide strong support for the clinical application of antibiotics and the development of new drugs. Full article

Pharmaceutical waste is a type of bio-waste inevitably generated by the pharmaceutical industry, often due to regulatory changes, product deterioration, or expiration. However, their collection and valorization can be approached from a sustainable perspective, offering potential energy-efficient solutions. In this work, the expired Eslicarbazepine acetate drug (ESLD) was utilized as a sustainable anticorrosive agent against mild steel in a 3 M HCl wash solution. Experimental tests combined with theoretical Density Functional Theory (DFT) and Monte Carlo (MC) simulations revealed the corrosion inhibition potential of ESLD. The gasometrical results revealed a high inhibition efficiency rate of 98% upon increases in concentration of expired ESLD from 0.25 to 1.00 mg·L⁻¹, whereas hydrogen gas evolution decreased to 0.7 mL. An impedance investigation evidenced the pivotal role of charge transfer in reducing the disintegration process. As per DFT computations and MC simulation, electron-rich elements in the expired ESLD were key in controlling the dissolution through the adsorption process. Contact angle studies revealed that the increment in the contact angle from 61° to 80° in the presence of expired ESLD validates the chemical, electrochemical, and computational results. This approach not only mitigates pharmaceutical pollution, but also exemplifies the integration of green chemistry principles into corrosion protection, contributing to energy-efficient and sustainable industrial practices. Full article

In the field of biomedical engineering, the issue of drug delivery constitutes a multifaceted and demanding endeavor for healthcare professionals. The intravenous administration of pharmacological agents to patients and the normalization of average arterial blood pressure (AABP) to desired thresholds represents a prevalent approach employed within clinical settings. The automated closed-loop infusion of vasoactive drugs for the purpose of modulating blood pressure (BP) in patients suffering from acute hypertension has been the focus of rigorous investigation in recent years. In previous works where model-based and fuzzy controllers are used to control AABP, model-based controllers rely on the precise mathematical model, while fuzzy controllers entail complexity due to rule sets. To overcome these challenges, this paper presents an adaptive closed-loop drug delivery system to control AABP by adjusting the infusion rate, as well as a communication time delay (CTD) for analyzing the wireless connectivity and interruption in transferring feedback data as a new insight. Firstly, a nonlinear backstepping controller (NBC) is developed to control AABP by continuously adjusting vasoactive drugs using real-time feedback. Secondly, a model-free deep reinforcement learning (MF-DRL) algorithm is integrated into the NBC to adjust dynamically the coefficients of the controller. Besides the various analyses such as normal condition (without CTD strategy), stability, and hybrid noise, a CTD analysis is implemented to illustrate the functionality of the system in a wireless manner and interruption in real-time feedback data. Full article

Liposome-based drug delivery technologies have showed potential in enhancing medication safety and efficacy. Innovative drug loading and release mechanisms highlighted in this review of next-generation liposomal formulations. Due to poor drug release kinetics and loading capacity, conventional liposomes have limited clinical use. Scientists have developed new liposomal carrier medication release control and encapsulation methods to address these limits. Drug encapsulation can be optimized by creating lipid compositions that match a drug’s charge and hydrophobicity. By selecting lipids and adding co-solvents or surfactants, scientists have increased drug loading in liposomal formulations while maintaining stability. Nanotechnology has also created multifunctional liposomes with triggered release and personalized drug delivery. Surface modification methods like PEGylation and ligand conjugation can direct liposomes to disease regions, improving therapeutic efficacy and reducing off-target effects. In addition to drug loading, researchers have focused on spatiotemporal modulation of liposomal carrier medication release. Stimuli-responsive liposomes release drugs in response to bodily signals. Liposomes can be pH- or temperature-sensitive. To improve therapeutic efficacy and reduce systemic toxicity, researchers added stimuli-responsive components to liposomal membranes to precisely control drug release kinetics. Advanced drug delivery technologies like magnetic targeting and ultrasound. Pro Drug, RNA Liposomes approach may improve liposomal medication administration. Magnetic targeting helps liposomes aggregate at illness sites and improves drug delivery, whereas ultrasound-mediated drug release facilitates on-demand release of encapsulated medicines. This review also covers recent preclinical and clinical research showing the therapeutic promise of next-generation liposomal formulations for cancer, infectious diseases, neurological disorders and inflammatory disorders. The transfer of these innovative liposomal formulations from lab to clinical practice involves key difficulties such scalability, manufacturing difficulty, and regulatory limits. Full article

Background: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3′-processing (3′P), thereby establishing its dual-targeting capability. Methods: The inhibitory activity of Zinc C295 against 3′P was evaluated using a modified in vitro assay adapted from our earlier ST inhibition studies. Molecular docking and molecular dynamics simulations were employed to analyse Zinc C295’s interactions with the 3′P allosteric site of HIV-1 integrase. Results: Zinc C295 demonstrated significant inhibition of HIV-1 integrase 3′P activity in in vitro assays (IC50 = 4.709 ± 0.97 µM). Computational analyses revealed key interactions of Zinc C295 within the enzyme’s allosteric site, providing insights into its dual inhibitory mechanism. Conclusions: Zinc C295’s dual inhibition of HIV-1 integrase ST and 3′P establishes it as a promising candidate for next-generation ART. Its dual-action mechanism may offer potential advantages in enhancing treatment efficacy and addressing drug resistance. Further studies are warranted to evaluate its therapeutic potential in clinical settings. Full article

The paulownia tree belongs to the Paulowniaceae family. Paulownia has strong vitality; has strong adaptability to harsh environmental conditions; and can be used as building raw material, as well as processing drugs and having other purposes. In the research field of MYB transcription factors of the paulownia tree, it is rare to discuss the resistance to abiotic stress. The research in this area has not received sufficient attention and depth, which also indicates an important potential direction for future research. In this study, we performed bioinformatics analysis of the stress-related gene PfMYB90, a potential transcription factor, and investigated its mechanism of action under salt and cold stresses. PfMYB90 was strongly expressed in the fully unfolded leaf and root of plants in both stress treatments. Transgenic PfMYB90 Arabidopsis plants had a greater survival rate under salt and cold stresses, and the degree of leaf damage was comparatively smaller, according to phenotypic observation and survival rate calculations. By measuring the corresponding physiological indexes after stress and detecting the expression levels of corresponding stress genes (AtNHX1, AtSOS1, AtSOS2, AtSOS3, AtCBF1, AtCBF3, AtCOR15a, AtRD29a), it was found that after PfMYB90 gene transfer, Arabidopsis showed strong tolerance to salt and cold stresses. This is consistent with the results mentioned above. This transgenic technology enables Arabidopsis to survive under adverse environmental conditions, allowing it to maintain a relatively stable growth state despite salt accumulation and cold stress. Therefore, PfMYB90 may be a key gene in the regulatory network of salt damage and cold damage, as well as one of the key transcription factors for Paulownia fortunei environmental conditions. Full article

Mycophenolic acid (MPA) is a commonly used immunosuppressant. In the human body, MPA is metabolized into mycophenolic acid 7-O-glucuronide (MPAG) and mycophenolic acid acyl-glucuronide (AcMPAG) mainly through liver glucuronidation, which involves UDP-glucuronosyltransferase (UGTs) and transfer proteins. Research has indicated that the pharmaceutical excipient PEG400 can impact drug processes in the body, potentially affecting the pharmacokinetics of MPA. Due to the narrow therapeutic window of MPA, combination therapy is often used, and PEG400 is widely used in pharmaceutical preparations. Therefore, investigating the pharmacokinetic influence of PEG400 on MPA could offer valuable insights for optimizing MPA’s clinical use. In this study, we examined the impact of a single oral dose of PEG400 on the blood levels of MPA in rats through pharmacokinetic analysis. We also investigated the distribution of MPA in various tissues using mass spectrometry imaging. We explored the potential mechanism by which PEG400 affects the metabolism of MPA using hepatic and intestinal microsomes and the Caco-2 cellular transporter model. Our findings reveal that the overall plasma concentrations of MPA were elevated in rats following the co-administration of PEG400, with the AUC_0-t of MPA and its metabolite MPAG increasing by 45.53% and 29.44%, respectively. Mass spectrometry imaging showed increased MPA content in tissues after PEG400 administration, with significant differences in the metabolites observed across different tissues. Microsomal and transport experiments showed that PEG400 accelerated the metabolism of MPA, promoted the uptake of MPA, and inhibited efflux. In conclusion, PEG400 alters the in vivo metabolism of MPA, potentially through the modulation of metabolic enzymes and transport. Full article

This study examines the prevalence and the mechanisms of antibiotic resistance in Pseudomonas aeruginosa isolates collected from healthcare units in Northwestern Transylvania, Romania, between 2022 and 2023. Given the alarming rise in antibiotic resistance, the study screened 34 isolates for resistance to 10 antibiotics, 46 ARGs, and integrase genes using PCR analysis. The results reveal a concerning increase in multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates over the two-year period. Notably, the prevalence of ARGs encoding resistance to sulfonamides and beta-lactams, particularly sul1 and bla_OXA-50, has shown a significant rise. Furthermore, the study detected the emergence of new resistance mechanisms in the same time interval. These include target protection and even more specific mechanisms, such as metallo-beta-lactamases or enzymes involved in the methylation of 23S rRNA. Statistical analysis further confirmed the correlation between Class I integrons and several ARGs, underscoring the role of horizontal gene transfer in the dissemination of resistance. These findings emphasize the urgent need for updated treatment strategies and monitoring programs to effectively combat the spread of ARGs in clinical settings. Full article