Search Results (6,767)

Essential oils from the genus Piper are recognized for their chemical diversity and biological potential, yet Piper platylobum has been scarcely investigated. This study aimed to characterize the chemical composition of the leaf essential oil of P. platylobum and evaluate its antimicrobial, antioxidant, and anticholinesterase activities. The oil was obtained by steam distillation and analyzed through gas chromatography–mass spectrometry (GC-MS) and gas chromatography equipped with a flame ionization detector (GC-FID), leading to the identification of 35 compounds that accounted for 91.11% of the volatile fraction. Dillapiole (42.0%) was the principal constituent, followed by α-(E)-bergamotene (5.69%), (E)-caryophyllene (5.01%), and (E)-isocroweacin (3.75%). Biological assays revealed selective antimicrobial activity, with inhibition observed only against Enterococcus faecium (MIC = 1000 µg/mL), while no effect was detected against other bacterial or fungal strains tested. Antioxidant evaluation showed moderate activity in the ABTS assay (SC₅₀ = 335.71 ± 1.43 µg/mL; TEAC = 45.85 ± 1.68 µM Trolox/g EO), but no activity in the DPPH assay. The essential oil also displayed moderate inhibition of acetylcholinesterase (IC₅₀ = 76.86 ± 1.00 µg/mL), suggesting a potential role in neuroprotective applications. This study constitutes the first report on the chemical composition and biological activities of P. platylabum essential oil, highlighting its potential as a novel source of bioactive compounds. Full article

The rising resistance of bacterial and fungal strains, particularly in biofilm form, is diminishing the efficacy of available therapies and poses a major threat to human health. This highlights the need for new antimicrobial agents. A review of biological studies has shown that 2,7-naphthyridine derivatives exhibit a wide spectrum of pharmacological properties, including antimicrobial activity, which has contributed to the development of new compounds containing this scaffold. In this work, the obtained compounds were tested to assess their ability to eradicate biofilm formed by selected reference strains of opportunistic pathogens: Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans as well as towards normal microbiota representative, referred to as the Lactobacillus crispatus. The tested 2,7-naphthyridine derivatives showed selective antimicrobial activity, exclusively against S. aureus. 10j demonstrated the highest, among tested compounds, activity on this pathogen (MIC = 8 mg/L), while compound 10f exhibited ~100-fold stronger activity (MIC = 31 mg/L) than the majority of the library compounds. The in vitro assessment on fibroblast cell lines demonstrated low cytotoxicity of both compounds 10f and 10j, which was subsequently confirmed in vivo using the Galleria mellonella larval model, where no signs of systemic toxicity were observed during the 5-day observation period. Due to the structural similarity of the compounds 10f and 10j to typical gyrase/topoisomerase IV inhibitors, molecular dynamics simulations were performed on a ternary complex containing protein, DNAds, and a 1,5-naphthyridine inhibitor (PDB ID: 6Z1A). Molecular dynamics of the gyrase–DNA ternary complex supported stable binding of both hydrazone derivatives, with 10j showing slightly more favorable MM/GBSA energetics driven by electrostatics and halogen bonding, consistent with its ~4-fold lower MIC versus 10f. Taken together, our data highlight compound 10j as a promising microbiota-sparing antibacterial candidate, particularly suitable for selective interventions against S. aureus, for instance in vaginal infections, where targeted eradication of the pathogen without disturbing protective commensals is highly desirable. Full article

Saudi Arabia has a large part of the country’s power consumption in the building area, mainly operated by cooling demands under extreme climatic conditions, where the summer temperature is more than 45 °C and solar radiation peaks are more than 1200 W/MIC. Facing this challenge, this research examines the translation of biometric principles in the design of adaptive building construction for dry areas. We present a comprehensive, four-phase method structure: removing thermoregulatory and shading strategies from desert vegetation; computer display simulation using EnergyPlus 9.7.0 and CFD (ANSYS Fluent 2022 R2); and the development of an implementation guideline. Our findings achieve three central insights. First, the dynamic factor system, such as the electrochromic glazing tested in our student project, reduced the use of HVAC energy by 30%, while advanced materials, such as the polycarbonate panel, demonstrated notable thermal stability. Secondly, the synergy between cultural knowledge and technical performance proved to be decisive; vernacular-inspired Mushrabias improved generic louver not only in thermal efficiency but also in user acceptance, which increased the 97% approval rate in post-acquisition surveys. Finally, we demonstrate that scalability is economically viable, indicating a seven-year payback period for simulation, phase-transit material (PCM), which aligns with the budgetary realities of public and educational projects. By fusing the plant-induced strategies with rigorous computational modeling and real-world applications, the work provides actionable guidelines for permanent failure design in the warm-dry climate. It underlines that maximizing energy efficiency requires the cohesion of thermodynamic principles with the craft traditions of local architecture, an approach directly aligned with the Saudi Green Initiative and the ambitions of global carbon neutrality goals. Full article

Background/Objectives: Altered bone metabolism and oxidative stress are features of autosomal dominant polycystic kidney disease (ADPKD). Pentosidine, an advanced glycation end-product and a marker of oxidative stress, has been proposed as an indicator of impaired bone health. This study aimed to evaluate whether pentosidine levels are altered in ADPKD and whether they are associated with bone characteristics in comparison with other chronic kidney disease (CKD) etiologies and healthy individuals. Methods: We conducted a cross-sectional analysis of three cohorts comprising 554 adults. Participants were categorized by CKD etiology and stage (G1–G5). ADPKD stages were classified according to the Mayo Imaging Classification (MIC). Plasma pentosidine was analyzed by HPLC and ELISA. Bone material strength index (BMSi) was assessed using a microindentation technique (OsteoProbe^®). Results: Plasma pentosidine was higher in ADPKD compared with other CKD etiologies in CKD stages G1–G4 (p = 0.023) and CKD 5D (p < 0.0001). Pentosidine was not associated with conventional bone biomarkers. However, in ADPKD individuals with preserved kidney function, higher pentosidine was associated with bone mineral density at the 1/3 radius and with BMSi. Conclusions: Pentosidine levels are consistently elevated in ADPKD compared with other CKD etiologies. Associations between pentosidine and measures of cortical bone properties suggest that pentosidine may contribute to skeletal alterations in ADPKD. These findings highlight a novel pathway linking oxidative stress and bone health. Full article

Drug-resistant Mycobacterium tuberculosis (Mtb) remains a major global health challenge, prompting the need for new therapeutics targeting essential bacterial proteins. The caseinolytic protein C1 (ClpC1) is a promising drug target, and accurate measurement of its ATPase activity is critical for understanding drug mechanisms. We optimized a sensitive luminescence-based ATPase assay and evaluated ClpC1 constructs with various tag positions and truncations. N-terminal tagging significantly impaired enzymatic activity, whereas C-terminal tagging had no effect; truncated domains showed reduced activity compared to native full-length (FL) ClpC1. Using the native FL-ClpC1, we assessed ecumicin (ECU) and five analogs via ATPase activity and surface plasmon resonance (SPR), using rufomycin (RUF) and cyclomarin A (CYMA) as controls. RUF and CYMA bound tightly (K_D = 0.006–0.023 µM) and inhibited Mtb growth (MIC₉₀ = 0.02–0.094 µM) but modestly stimulated ATPase activity (≤2-fold). In contrast, ECU and its analogs strongly enhanced ATPase activity (4–9-fold) despite slightly weaker binding (K_D = 0.042–0.80 µM) and growth inhibition (MIC₉₀ = 0.19 µM). The partial correlation among AC₅₀, K_D, and MIC values highlights the complementary value of enzymatic, biophysical, and cellular assays. Our assay platform enables mechanistic characterization of ClpC1-targeting compounds and supports rational antitubercular drug development. Full article

Background and Objectives: Catheter-associated urinary tract infections (CAUTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) significantly contribute to global rates of UTI. This study aimed to compare the prevalence and trends of ESBL-producing Enterobacterales and CRE in patients with CAUTIs and non-CAUTIs. Materials and Methods: A retrospective review of 4262 UTI-positive urine cultures was conducted at King Fahad Hospital of the University, Al Khobar, Saudi Arabia (January 2022–November 2023). Demographic, clinical, and microbiological data were obtained from hospital records. Antimicrobial susceptibility was tested using the Vitek^® System; ESBL and CRE were identified using Ezy MIC™ strips and Xpert^® Carba-R assay, respectively. Results: ESBL-producing Enterobacterales accounted for 11.3% of cases; CRE comprised 1.8%. ESBL was significantly more prevalent in non-catheterized patients and those in emergency care. CRE was significantly associated with catheterized patients and inpatient settings. Escherichia coli and Klebsiella pneumoniae were the predominant ESBL-producing and CRE isolates, respectively. bla-OXA-48 was the most frequently detected carbapenemase gene (66.7%). ESBL was prevalent in younger, non-catheterized females, suggesting increasing community transmission. Conversely, CRE were primarily observed in older, catheterized inpatients, emphasizing the role of invasive devices in resistance spread. Conclusions: These findings highlight the importance of targeted infection control and early catheter removal to mitigate resistance trends. Full article

Mycobacterium avium is an opportunistic pathogen and a leading contributor to nontuberculous mycobacterial infections in immunocompromised individuals. However, treatment duration, antibiotic toxicity, and resistance present challenges in the management of mycobacterium infections, prompting the need for novel treatment. N-acetylcysteine (NAC) has demonstrated potent antimycobacterial activity, while antimicrobial peptides such as the cyclic [R₄W₄] have shown additive effects when combined with first-line antibiotics. This study aimed to investigate the mechanism and efficacy of NAC and [R₄W₄] combination therapy against M. avium. A membrane depolarization assay was used to evaluate the effects of NAC and [R₄W₄] on M. avium cell membrane integrity. Antimycobacterial activity was assessed by treating cultures with varying concentrations of NAC, [R₄W₄], a combination, or a sham treatment. The same regimens were applied to M. avium-infected THP-1-derived macrophages to assess intracellular efficacy. NAC and [R₄W₄] each disrupted the M. avium membrane potential, with enhanced effects in combination. The combination treatment significantly reduced M. avium survival in both the culture and infected macrophages compared with NAC alone and untreated controls. [R₄W₄] and NAC also demonstrated potent antibacterial activity, while the lowest MIC and the combination of [R₄W₄] and NAC displayed additive effects, indicating an improved bacterial inhibition compared to individual treatments. These findings demonstrate the additive activity of NAC and [R₄W₄] against M. avium in vitro and suggest that combining antioxidant compounds with antimicrobial peptides may represent a promising strategy for treating mycobacterial infections. Full article

Porcine extraintestinal pathogenic Escherichia coli (ExPEC) is a significant zoonotic pathogen with escalating antimicrobial resistance, underscoring the urgent need for novel therapeutics. This study aimed to investigate the therapeutic potential and mechanism of action of the antimicrobial peptide Protegrin-1 (PG-1) against a multidrug-resistant porcine ExPEC strain, PCN033. The minimal inhibitory concentration (MIC) was determined, and resistance stability was assessed through serial induction and withdrawal passages. Hemolytic activity was evaluated to gauge selectivity. A murine infection model was utilized to assess in vivo efficacy, bacterial load reduction, cytokine modulation, and histopathology. Comparative spleen transcriptomic analysis was performed to elucidate global host responses. PG-1 exhibited potent bactericidal activity (MIC = 32 μg/mL) and maintained its efficacy over multiple passages, demonstrating no induced resistance. It showed acceptable hemolytic activity and significantly improved survival, reduced bacterial loads in multiple organs, and mitigated tissue damage in mice. Transcriptomics revealed PG-1 treatment broadly tempered infection-induced hyperinflammatory responses, including NF-κB, MAPK, and TNF signaling pathways, and counteracted metabolic reprogramming. The findings conclude that PG-1 effectively integrates direct, resistance-resistant bactericidal activity with multimodal immunomodulation, representing a superior therapeutic strategy that simultaneously eliminates pathogens and restores immune homeostasis, offering a promising alternative to conventional antibiotics against MDR ExPEC infections. Full article

Background: Iron oxide nanoparticles (IONPs) have broad-spectrum antimicrobial activity, with negligible potential for resistance development, excellent biocompatibility, and therefore, could be promising alternatives to conventional antimicrobials. However, their industrial-scale production relies on chemical synthesis that involves toxic reagents, imposing potential environmental hazards. In contrast, green synthesis offers an eco-friendly alternative, but our previous study found that green-synthesized IONPs (IONPs-G) exhibited a lower antibacterial activity and a higher cytotoxicity compared to chemically synthesized counterparts, likely due to nanoparticle aggregation. Objectives: To address this challenge, the current study presents a simple, effective, economic, scalable, and eco-friendly strategy to optimize the physicochemical properties of IONPs-G post-production without requiring extensive modifications to synthesis parameters. Methods: IONPs-G were dispersed in a solvent mixture containing Tween 80 (Tw80). Subsequently, in vitro antimicrobial and in vivo cytotoxicity studies on rabbits’ skin and eye were conducted. Results: The formed nanoparticles’ dispersion (IONPs-GTw80) had a particle size of 9.7 ± 2.1 nm, a polydispersity index of 0.111 ± 0.02, and a zeta potential of −11.4 ± 2.4 mV. MIC of IONPs-GTw80 values against S. aureus and E. coli were reduced by more than ten-fold compared to IONPs-G. MBC was twice MIC, confirming the bactericidal activity of IONPs-GTw80. In vivo studies of IONPs-GTw80 confirmed their biocompatibility with intact/abraded skin and eyes; this was further confirmed by histopathological and biochemical analyses. Conclusions: IONPs-GTw80 might be recommended as a disinfectant in healthcare settings or a topical antimicrobial agent for treatment of infected wounds. Nevertheless, further studies are required for their clinical translation. Full article

Antimicrobial resistance (AMR) poses a major global threat to human health. Among multidrug-resistant pathogens, MRSA is a leading cause of severe nosocomial infections, urgently demanding the discovery of novel antimicrobial agents. Nature, particularly Actinomycetota, remains a prolific source of potent bioactive compounds to combat pathogens. This review analyzes recent advancements in anti-MRSA compounds from Actinomycetota. We highlight the most promising bioactive metabolites, their sources, mechanisms of action, and current limitations. Our analysis identified numerous compounds with potent activity against MRSA, including chromomycins, actinomycins, diperamycin, lunaemycin A, lactoquinomycin A, and weddellamycin, which exhibit submicromolar minimal inhibitory concentrations (MICs). The renewed interest in exploring Actinomycetota de novo is directly driven by the AMR crisis. Furthermore, bioprospecting efforts in underexplored ecological niches, such as mangroves and marine sediments, have proven highly promising, as these habitats often harbour unique microbial communities producing novel metabolites. These findings underscore the critical importance of ecology-driven drug discovery in expanding the antimicrobial arsenal and effectively addressing the global health challenge of MRSA and other resistant pathogens. Full article

The reaction of imidazole-5-carbohydrazide 1 with hydrazonyl halides 2a,b gave the corresponding hydrazide–hydrazone derivatives 3a,b. Afterwards, 3-methyl-5-(4-methyl-2-aryl-1H-imidazol-5-yl)-4-(2-phenylhydrazineylidene)-4H-pyrazole 4a,b was affordably produced by cyclizing the latter compounds 3a,b in EtOH with Et₃N at reflux temperature. The corresponding piperidinyl, morpholinyl, and piperazinyl derivatives 5a–f were produced by a nucleophilic substitution reaction of 3a,b with piperidine, morpholine, and 1-methylpiperazine in EtOH at reflux temperature. The condensation reaction of carbohydrazide 1 with either 3-acetyl-2H-chromen-2-one or 1-(benzofuran-2-yl)ethan-1-one in EtOH with AcOH at reflux temperature yielded the corresponding hydrazones 6 and 7, respectively, in excellent yields. Twelve compounds were evaluated for their antibacterial properties and to ascertain their minimum inhibitory concentrations utilizing well diffusion methods. All compounds showed differing levels of antibacterial efficacy depending on the microbial species. Compounds 4b and 5c had the most favorable results, with inhibition zones of 2.7 cm against the Gram-positive bacterium S. aureus, with a minimum inhibitory concentration (MIC) of 50 µg/mL. Compounds 4b and 5c, demonstrating the highest activity, were subjected to molecular docking investigations to evaluate their inhibitory effects on the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase [GlcN-6-P] of 2VF5. The molecular docking results revealed that both 4b and 5c exhibited a minimum binding energy of −8.7 kcal/mol, whereas the natural ligand GLP displayed a binding energy of −6.2 kcal/mol, indicating a substantial affinity for the active site; thus, they may be considered potent inhibitors of GlcN-6-P synthase. Full article

Plant secondary metabolites are an interesting source of natural antifungals and offer an alternative to synthetic preservatives. In this study, the activity of 218 secondary metabolites was evaluated against nine Penicillium species and one Aspergillus species, isolated from spoiled par-baked bread. By comparing agar and liquid-based assays, it was found that the hydrophobic nature of these compounds led to an underestimation of the activity in agar-based assays. In liquid medium, it was possible to evaluate the effect quantitatively and differentiate between strong and weak inhibitors. Of the most interesting compounds, the minimal inhibitory concentration (MIC) was determined, and synergistic interactions were studied. This revealed an interesting interaction between benzyl isothiocyanate and carvacrol, which was further investigated through validation in par-baked bread. Antifungal efficacy was assessed in a shelf life and challenge test, revealing that spray application of 200 to 400 µg/mL benzyl isothiocyanate and 1000 to 2000 µg/mL carvacrol significantly increased shelf life. Furthermore, application of benzyl isothiocyanate and carvacrol was as effective as 0.15% propionic acid was incorporated in the dough. A sensory triangle test indicated that benzyl isothiocyanate and carvacrol influenced the flavour of fully baked bread; however, the effect was not perceived negatively. Full article

Chemical disinfection of removable acrylic dental prostheses minimizes the risk of denture stomatitis caused by the opportunistic fungal pathogen Candida albicans. We previously reported that neutral-pH electrolysed oxidising water (EOW), a hypochlorous acid (HOCl)-based biocide, is effective at inhibiting C. albicans biofilm formation on denture resins. Knowledge about the mechanism of action of EOW on C. albicans is lacking. This study investigated the molecular mechanism of action of neutral-pH EOW against C. albicans cells that were incubated with sub-inhibitory concentrations of EOW-HOCl (treatment with 0.125× MIC₉₀ EOW-HOCl (15 µM; T0.125) or treatment with 0.5× MIC₉₀ EOW-HOCl (59 µM; T0.5)). RNA-sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs) which were validated by qRT-PCR. Ninety-five DEGs were identified between the treated and untreated cells after a 60 min exposure. A moderate sub-inhibitory EOW-HOCl concentration (T0.125) caused significant upregulation (log₂ fold change > +2) of genes responsive to oxidative stress (EBP1, GAP6, PRN1, HSP21), weak organic acid stress (PRN1), and heat-shock (HSP21). A higher sub-inhibitory concentration (T0.5) caused a significant downregulation of most DEGs (notably, −1.9 to −3 log₂ fold reduction in SUT1, HNM3, STP4 expression), cessation of growth, and an upregulation of genes involved in ammonia transport, carbohydrate metabolism, and the unfolded protein and apoptotic response pathways (ATO2, IRE1). Our findings reveal HSP21 and PRN1 to be possible key players in protecting C. albicans cells against HOCl, a natural biocide of the innate immune system. Full article

Wound infections pose a significant challenge in modern medicine, driven by multimorbidity, weakened immunity, microbial virulence factors, and resistance to antibiotics and antiseptics. This study aims to evaluate the antibacterial properties of carvacrol (CAR), its impact on biofilm formation, and its capacity to trigger oxidative stress in clinical strains of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter cloacae. Carbapenemases in the studied bacteria were detected using culture on CarbaId agar. The presence of genes encoding bacterial virulence factors and carbapenemase production was confirmed using the PCR method. The antimicrobial activity of carvacrol was evaluated using the broth microdilution method. The ability of strains to form biofilm was determined using a modified crystal violet assay. Oxidative stress levels in bacterial cells in response to carvacrol treatment were measured using 2′,7′-dichlorofluorescein diacetate. Real-TimePCR was used to confirm the presence of NDM family carbapenemase genes in K. pneumoniae strains, KPC genes in E. cloacae strains, and VIM genes in P. aeruginosa strains. CAR exhibited a broad spectrum of antibacterial activity against the tested bacteria, with MIC values ranging from 125 to 1000 μg/mL. Treatment with 1/2 MIC of CAR did not significantly influence biofilm formation, except in a K. pneumoniae isolate. At 1/2 MIC, CAR induced an increase in intracellular ROS in most tested strains, with the exception of P. aeruginosa 25521221. This study provides insights into the antimicrobial efficacy of carvacrol against carbapenemase-producing pathogens isolated from wound infections—specifically P. aeruginosa, K. pneumoniae, and E. cloacae. CAR demonstrated promising bactericidal properties, likely mediated through the induction of oxidative stress, as evidenced by increased ROS generation in most studied isolates. Full article

Silver nanoparticles (AgNPs) are valued for their antimicrobial properties, but conventional synthesis often involves toxic chemicals. Eco-friendly biosynthesis using silver-tolerant microbes from contaminated sites offers a sustainable alternative. This study biosynthesized and characterized AgNPs using a native Bacillus sp. from contaminated soil in the Jazan region, Saudi Arabia, and developed predictive models for optimizing synthesis and antimicrobial activity. AgNPs were synthesized under optimized conditions (1.0 mM AgNO₃, 4.0 mL supernatant, pH 8, 85 °C). Characterization using UV–Vis, SEM, TEM, XRD, and FTIR assessed size, shape, structure, and chemistry. Gaussian and second models evaluated yield and inhibition zones based on AgNP concentration, microorganism type, and MIC. The AgNPs were spherical with diameters of 5–10 nm. The optimal nanoparticle yield occurs when the parameters are at their optimal values; C₀ = 1.0 mM, V₀ = 4.0 mL, pH₀ = 8, T₀ = 85 °C. XRD confirmed their crystalline nature, and FTIR showed biomolecular capping agents for stabilization. The Gaussian model accurately predicted synthesis efficiency, validated by 3D plots matching experimental data. The AgNPs showed strong antimicrobial activity against Gram-positive (Bacillus subtilis) (ATCC6051), Staphylococcus aureus (ATCC12600), Gram-negative bacteria Escherichia coli (ATCC11775) and fungi Candida albicans (ATCC10231); with E. coli having the lowest MIC (1.87 μg/mL). The inhibition zone model closely matched observed data. Biosynthesized AgNPs using silver-tolerant Bacillus sp. demonstrated potent antimicrobial effects and provide a green alternative to chemical synthesis. Integrating modeling optimizes biosynthesis and predicts biological performance, supporting future nanobiotechnology and antimicrobial applications. Full article