Search Results (21,040)

Staphylococcus aureus is a major opportunistic pathogen responsible for a wide spectrum of human infections, including severe and difficult-to-treat cases. The emergence of multidrug-resistant strains limits the efficacy of conventional antibiotic therapies and poses a significant global public health challenge. In this context, the search for novel antibiotics has intensified, with increasing interest in marine resources, an ecosystem still largely underexplored. Marine bacteria produce a vast array of secondary metabolites with unique structures and potentially novel modes of antibacterial action. Several compounds isolated from marine bacterial strains have demonstrated promising activity against multidrug-resistant S. aureus, including antivirulence effects such as biofilm formation and Quorum-Sensing inhibition. This review explores the potential of marine bacteria as a source of new antibiotics against S. aureus, discusses both classical and advanced strategies for the discovery of bioactive molecules, and highlights the scientific and technological challenges involved in translating these findings into clinical applications. Full article

Glycosylation serves as an effective strategy to enhance the solubility, bioavailability, and pharmacological activity of polyhydroxyphenols. In this study, we explored the glycosylation of natural and natural-inspired phenolic compounds using the glycosyltransferase AbCGT and evaluated the anti-renal fibrotic potential of the resulting glycosides. Among them, 1,3,5,8-tetrahydroxyxanthone 5-O-β-D-glucopyranoside (2-1a), synthesized via the regioselective 5-O-glycosylation of demethylbellidifolin, demonstrated significant anti-renal fibrotic activity. In contrast, its homologous glycosyltransferase, UGT73AE1, predominantly glycosylated demethylbellidifolin at the 3-OH position. Molecular docking studies revealed the structural basis for this regioselectivity difference. To enhance the production of 2-1a, we established a UDP-glucose (UDPG) recycling system by coupling AbCGT with Glycine max sucrose synthase (GmSuSy) and subsequently optimized the reaction conditions. Furthermore, targeted mutagenesis of AbCGT informed by molecular docking analysis identified a F138A mutant that enhanced glycosylation yield by 2.3-fold. This work develops a novel glycosyltransferase-based catalytic system and identifies a new compound with potential anti-renal fibrotic activity. Full article

Type 2 diabetes mellitus (T2DM) is a multifaceted metabolic disorder marked by impaired insulin action, pancreatic β-cell dysfunction, and the involvement of several interconnected mechanisms, including inflammation, oxidative stress, and epigenetic alterations. Despite progress in conventional therapies, achieving durable glycemic control and minimizing complications remain major challenges. This review discusses the emerging role of bioactive phytochemicals—such as curcumin, berberine, resveratrol, flavonoids, and polysaccharides—in modulating essential molecular pathways including AMPK, PI3K/AKT, and cAMP/PKA, which contribute to enhanced insulin sensitivity, glucose regulation, and β-cell protection. These natural compounds also influence gut microbiota modulation and epigenetic mechanisms, offering additional metabolic and anti-inflammatory benefits. This review synthesizes evidence from peer-reviewed studies published between 2000 and 2024, incorporating bibliometric trends showing an increasing research focus on phytochemicals for T2DM management. However, limitations such as low solubility, instability, and poor absorption restrict their clinical application. Advances in nanotechnology-based delivery systems, including nanoparticles, liposomes, and nanoemulsions, have shown potential to overcome these barriers by improving stability, bioavailability, and targeted delivery of phytochemicals. The integration of gut microbiota modulation with nanocarrier-enabled phytochemical therapy supports a precision medicine approach for managing T2DM. Preliminary clinical evidence highlights significant improvements in glycemic control and inflammatory status, yet further large-scale, well-controlled trials are essential to ensure safety, optimize dosages, and standardize combination regimens. Overall, phytochemical therapies, reinforced by nanotechnology and microbiota modulation, present a promising, safe, and holistic strategy for T2DM management. Continued interdisciplinary research and clinical validation are crucial for translating these advances into effective therapeutic applications and reducing the global diabetes burden. Full article

Worldwide, prostate cancer (PC) has a rising incidence and is the sixth leading cause of death globally, especially with increasing cases in developing countries. Risk factors for PC include genetic predisposition, family history, race/ethnicity, and various occupational factors like diet, obesity, smoking, and transmitted diseases. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway can be activated by hormones, cytokines, and growth factors, and it plays a role in many vital biological processes such as cell growth, differentiation, immune regulation, and apoptosis. Dysregulation of JAK/STAT3 can lead to cancer, inflammation, diabetes, and neurodegenerative disorders. In cancers, including PC, STAT3 promotes cell survival, progression, angiogenesis, and metastasis. Inhibitors targeting JAK and STAT3 tested in vivo have shown potential to inhibit malignant cell growth. Additionally, flavonoids are bioactive plant compounds that are important in preventing inflammation, oxidative stress, and cancer. Research indicates that natural flavonoids can be developed into cancer-preventive and therapeutic agents. Experimental studies have demonstrated that some flavonoids can inhibit PC development. The main goal of this review is to present the incidence and risk factors of PC, the JAK/STAT3 pathway and its inhibitors, and how flavonoids may influence this pathology. Full article

The ecdysteroid receptor (EcR) plays a crucial role in insect development and metamorphosis, making it a promising target for the design of novel biorational compounds. This study investigated the cytotoxicity, as well as the EcR agonist and antagonist activities, of three synthetic molecules analogous to tebufenozide and extracts from nine plant species using the dipteran S2 cell line which originates from the insect model of the fruit fly Drosophila melanogaster. Cytotoxicity assays were performed to determine appropriate concentrations of the synthetic molecules and plant extracts for cell transfection. EcR agonist and antagonist activities were evaluated using 20-hydroxyecdysone (20E) as the control hormone. The synthetic molecules analogous to tebufenozide did not activate EcR in S2 cells. In contrast, the plant extract of Neoblechnum brasiliense, commonly known as Brazilian dwarf tree fern, exhibited significant antagonistic activity at 100 µM, reducing receptor activity by 92%, likely due to its phytosteroid content, and without inducing cytotoxic effects. These findings demonstrate that certain plant extracts, particularly N. brasiliense, act as effective EcR antagonists and may represent promising natural leads for the development of environmentally compatible biorational compounds to control economically important dipteran pests, such as fruit flies and mosquitoes. Full article

Hawk tea (Litsea coreana Levl. var. lanuginosa), a naturally caffeine-free herbal beverage widely consumed in Southwest China, is characterized by a pronounced camphoraceous note that often deters first-time consumers. In this study, hawk tea leaves were subjected to solid-state fermentation with four microbial strains—Monascus purpureus, Aspergillus cristatus, Bacillus subtilis, and Blastobotrys adeninivorans. The volatile compounds of unfermented and fermented hawk teas were identified by ultra-fast gas chromatography electronic nose (ultra-fast GC e-nose), gas chromatography–mass spectrometry (GC-MS) and gas chromatography–ion mobility spectrometry (GC-IMS) analyses, respectively. Furthermore, the calculation of odor activity values (OAVs) and relative odor activity value (ROAV) revealed that 6 and 25 volatile chemicals, including perillaldehyde (OAV 3.692) and linalool (ROAV 100), were the main contributors to the floral, fruity, and woody aroma of fermented hawk tea. Sensory evaluation confirmed that fermentation generally enhanced woody notes while significantly reducing the characteristic camphoraceous and oil oxidation odors. Notably, the Blastobotrys adeninivorans-fermented sample exhibited the most pronounced floral and fruity nuances, accompanied by significantly elevated aroma complexity and acceptability. Consequently, Blastobotrys adeninivorans represents a promising starter culture for the improvement of hawk tea flavor. Full article

Canine ehrlichiosis, caused by Ehrlichia canis, represents a relevant challenge in veterinary medicine, particularly in resource-limited settings where access to laboratory-based diagnostics may be constrained. This pilot and exploratory study aimed to evaluate the feasibility of a portable electronic olfactometer as a non-invasive screening approach, based on the analysis of volatile organic compounds (VOCs) present in breath, saliva, and hair samples from dogs. Signals were acquired using an array of eight metal-oxide (MOX) gas sensors (MQ and TGS series). After preprocessing, principal component analysis (PCA) was applied for dimensionality reduction, and the resulting features were analyzed using supervised machine-learning classifiers, including AdaBoost, support vector machines (SVM), k-nearest neighbors (k-NN), and Random Forests (RF). A total of 38 dogs (19 PCR-confirmed infected cases and 19 controls) were analyzed, generating 114 samples evenly distributed across the three biological matrices. Among the evaluated models, SVM showed the most consistent performance, particularly for saliva samples, achieving an accuracy, sensitivity, and precision of 94.7% (AUC = 0.964). In contrast, breath and hair samples showed lower discriminative performance. Given the limited sample size and the exploratory nature of the study, these results should be interpreted as preliminary; nevertheless, they suggest that electronic olfactometry may represent a complementary, low-cost, non-invasive screening tool for future research on canine ehrlichiosis, rather than a standalone diagnostic method. Full article

Background: Nanotechnology provides innovative strategies to enhance drug delivery and therapeutic efficacy through advanced nanocarrier systems. Objectives: This study aimed to develop and optimize a nanostructured lipid carrier (NLC) co-encapsulating curcumin (CUR) and resveratrol (RESV) using a fractional factorial design to develop a topical formulation with antioxidant and anti-inflammatory properties. Methods: NLCs were produced via hot emulsification followed by high-pressure homogenization, and their physicochemical characteristics, drug content, stability, release profile, antioxidant activity, skin delivery, and cellular compatibility were evaluated. Results: The optimized formulation exhibited an average particle size of approximately 300 nm, a polydispersity index below 0.3, and high drug loading for both compounds. Stability studies over 90 days revealed no significant changes in physicochemical parameters, confirming the formulation’s robustness. In vitro release assays demonstrated sustained release of both actives, with 58.6 ± 2.9% of CUR and 97 ± 3% of RESV released after 72 h. Antioxidant activity, assessed by the DPPH and ABTS assays, showed concentration-dependent radical-scavenging effects, indicating antioxidant potential. Skin permeation/retention experiments using porcine skin showed enhanced retention of CUR and RESV within the tissue, with no detectable permeation, indicating suitability for topical delivery. In addition, in vitro cell assays using human keratinocytes showed concentration-dependent responses and acceptable cellular compatibility. Conclusions: Overall, this study demonstrates the successful application of nanotechnology and experimental design to develop stable and efficient lipid-based nanocarriers containing natural polyphenol for topical therapy targeting oxidative and inflammatory skin disorders. Full article

Polyphenols with antimicrobial and antibiofilm properties are gaining popularity due to their natural origins and relatively safe nature, and they have met the interest of the food industry because of their possible applicability as food preservatives. We have investigated the effect of different analogs of dimeric A-type proanthocyanidins (PACs) on four food matrix models, including unprocessed meat, fish, vegetables and dairy products previously contaminated with susceptible food pathogens. The best effects were achieved when cherry tomato was used as the food matrix for all the target bacteria (Staphylococcus aureus CECT 828, Listeria innocua CECT 910 and Bacillus cereus UJA27q) and for both temperatures tested (6 and 25 °C). Moreover, several combinations of these analogs also showed synergistic effects, mainly on S. aureus CECT 828, which may allow these antimicrobials to be used at lower levels in food matrices, which would promote their sensory acceptability. However, further studies should be conducted next to understand the mechanisms of these synergistic activities between the phenolic compounds against foodborne pathogens, as well as to ensure the absence of toxic effects when used as food preservatives. Full article

Pyrethroids, synthetic analogues of natural pyrethrins, are extensively used in agriculture and household pest control due to their high insecticidal activity and relatively low toxicity to mammals. Due to the presence of multiple chiral centres, many pyrethroids exist as complex mixtures of stereoisomers with significantly different biological activities, toxicities, and environmental behaviours. Consequently, accurate determination of these stereoisomeric forms, particularly compounds such as cypermethrin, is critical for food safety monitoring. Determining pyrethroid residues in food matrices presents a significant analytical challenge due to the structural diversity and stereochemical complexity of these compounds. This study presents the development of an analytical method for determining the stereoisomeric forms of cypermethrin and other synthetic pyrethroids in food matrices using both LC-MS/MS and GC-MS/MS techniques. The method meets the performance criteria outlined in SANTE/11312/2021 v2, demonstrating satisfactory recovery rates (91.6%), precision (RSDR 1.9%), and low limits of quantification (LOQ 0.010 µg/kg) for the quantification of alpha-cypermethrin. This approach offers a reliable tool for regulatory monitoring and risk assessment of pyrethroid residues, especially those with complex stereochemistry. Full article

Postbiotics, defined as non-viable microorganisms or their structural and metabolic components, have attracted attention for their documented health effects, including modulation of gut homeostasis and inflammatory responses. Tributyrin is among the most promising postbiotics studied, and its safety profile enables it to exert its beneficial effects. However, tributyrin activity must be maintained after its uptake, underscoring the importance of selecting appropriate delivery strategies, such as its incorporation into electrospun composites. Combining postbiotics and natural antioxidants, such as Spirulina and its components, to improve their properties can be a great strategy. Therefore, the present work aimed to produce tributyrin–Spirulina composites via electrospinning. The composites obtained were characterized, and their antioxidant activity and cytotoxicity were determined. All formulations were successfully produced by electrospinning, as the composites retained the bonds of their respective components. In terms of antioxidant activity, the combination of tributyrin and C-phycocyanin was the most promising among the bioactive compounds studied. Overall, the viability and cytotoxicity results indicate that interactions among bioactive composition, redox regulation, and adhesion-dependent survival govern cellular responses to electrospun zein fibers. Tributyrin promotes metabolic adaptation over time, whereas Spirulina-derived fractions are more sensitive to formulation and culture conditions. Full article

Multidrug resistance (MDR) is a central cause of chemotherapy failure and tumor recurrence and metastasis, and its mechanism involves enhanced drug efflux, target mutation, upregulation of DNA repair and remodeling of the tumor microenvironment. ABC transporter protein (P-gp, MRP, and BCRP)-mediated efflux of drugs is the most intensively researched aspect of the study, but the first three generations of small-molecule reversal agents were stopped in the clinic because of toxicity or pharmacokinetic defects. Natural products are considered as the fourth generation of MDR reversal agents due to their structural diversity, multi-targeting and low toxicity. In this paper, we systematically summarize the inhibitory activities of monoterpenes, sesquiterpenes, diterpenes and triterpenes against ABC transporter proteins in in vitro and in vivo models and focus on the new mechanism of reversing drug resistance by blocking efflux pumps, modulating signaling pathways such as PI3K-AKT, Nrf2, NF-κB and remodeling the tumor microenvironment. For example, Terpenoids possess irreplaceable core advantages over traditional multidrug resistance (MDR) reversers: Compared with the first three generations of synthetic reversers, natural/semisynthetic terpenoids integrate low toxicity (mostly derived from edible medicinal plants, half-maximal inhibitory concentration IC₅₀ > 50 μM), high target specificity (e.g., oleanolic acid specifically inhibits the ATP-binding cassette (ABC) transporter subtype ABCC1 without cross-reactivity with ABCB1), and multi-mechanistic synergistic effects (e.g., β-caryophyllene simultaneously mediates the dual effects of “ABCB1 efflux inhibition + apoptotic pathway activation”). These unique characteristics enable terpenoids to effectively circumvent key limitations of traditional synthetic reversers, such as high toxicity and severe drug–drug interactions. Among them, lupane-type derivative BBA and euphane-type sooneuphanone D (triterpenoids), as well as dihydro-β-agarofuran-type compounds and sesquiterpene lactone Conferone (sesquiterpenoids), have emerged as the core lead compounds with the greatest translational potential in current MDR reverser research, attributed to their potent in vitro and in vivo MDR reversal activity, low toxicity, and excellent druggable modifiability. At the same time, we point out bottlenecks, such as low bioavailability, insufficient in vivo evidence, and unclear structure–activity relationship and put forward a proposal to address these bottlenecks. At the same time, the bottlenecks of low bioavailability, insufficient vivo evidence and unclear structure–activity relationship have been pointed out, and future research directions such as nano-delivery, structural optimization and combination strategies have been proposed to provide theoretical foundations and potential practical pathways for the clinical translation research of terpenoid compounds, whose clinical application still requires further in vivo validation and translational research support. Full article

The increasing prevalence of multidrug-resistant (MDR) Campylobacter species poses a serious threat to food safety and public health, highlighting the urgent need for natural antimicrobial alternatives to conventional antibiotics. This study investigated the antibacterial potential and mechanism of action of seven essential oils (EOs), Cymbopogon citratus, Mentha pulegium, Artemisia absinthium, Myrtus communis, Thymus algeriensis, Thymus capitatus, and Eucalyptus globulus, against multidrug-resistant Campylobacter jejuni and Campylobacter coli. The antimicrobial activity was first assessed by the agar disk diffusion and broth microdilution methods to determine inhibition zones, minimum inhibitory concentrations (MICs), and minimum bactericidal concentrations (MBCs). The most active EOs were further evaluated through time–kill kinetics, cell lysis, salt tolerance, and membrane integrity assays to elucidate their bactericidal mechanisms. Results showed that E. globulus, T. algeriensis, and M. communis exhibited the strongest inhibitory effects, particularly against C. jejuni, with MIC values ranging from 3.125% to 6.25%, while C. coli was more resistant. Time–kill and lysis experiments demonstrated rapid bacterial reduction and significant decreases in optical density, indicating cell disruption. Additionally, EO treatments reduced salt tolerance and induced leakage of cytoplasmic materials, confirming membrane damage. Overall, these findings suggest that selected essential oils exert potent antimicrobial effects through membrane disruption and osmotic imbalance, offering promising natural strategies to control MDR Campylobacter in food systems. The application of such bioactive compounds could contribute significantly to improving food quality, extending shelf life, and enhancing food safety. Full article

The issue of formulating scientifically sound standards for mercury (Hg) content in Arctic soils is becoming increasingly pertinent in view of the rising human impact and climate change, which serve to augment the mobility of Hg compounds and their involvement in biogeochemical processes. In the absence of uniform criteria for regulating Hg concentrations, it is particularly important to determine its geochemical baseline values and the factors that determine the spatial and vertical distribution of the element in the soil profile. The study conducted a comprehensive investigation of Hg content and patterns of its distribution in various types of tundra soils in the European North-East of Russia. The mass fraction of total Hg was determined by atomic absorption spectrometry, and the spatial features of accumulation were analysed using geoinformation technologies. The distribution of Hg in the soils of the tundra zone was found to be distinctly mosaic in nature, determined by the combined influence of organic matter, granulometric composition, and hydrothermal conditions. It has been established that the complex influence of the physicochemical properties of soils determines the spatial heterogeneity of Hg distribution in the soils of the tundra zone. The most effective Hg accumulators are peat and gley horizons enriched with organic matter and physical clay fraction, while in Podzols, vertical migration of Hg is observed in the presence of a leaching water regime. In order to standardise geochemical baseline Hg values, a 95% upper confidence limit (UCL_95%) is proposed. This approach enables the consideration of natural background fluctuations and the exclusion of extreme values. The results obtained provide a scientific basis for the establishment of standards for Hg content in background soils of the Arctic. Full article

Background/Objectives: Obstructive sleep apnea (OSA) affects approximately 1 billion adults worldwide with extensive comorbidities, including cardiovascular disease, metabolic disorders, and cognitive decline, yet pharmacological therapies remain limited. Conventional bottom-up omics approaches identify numerous genes overlapping with other diseases, hindering therapeutic translation. This study introduces a top-down, comorbidity-driven approach to identify actionable molecular targets and develop rational dual kinase inhibitors for OSA management. Methods: We implemented a five-tier modeling workflow: (1) comorbidity network analysis, (2) disease module identification through NetworkAnalyst, (3) mechanistic pathway reconstruction of the CK1δ-(HIF1A)-PINK1 signaling cascade, (4) molecular docking analysis of Nigella sativa alkaloids and reference inhibitors (IC261, PF-670462) against CK1δ (PDB: 3UYS) and PINK1 (PDB: 5OAT) using AutoDock Vina, and (5) rational design and computational validation of novel dual inhibitors (ICL, PFL) integrating pharmacophoric features from natural alkaloids and established kinase inhibitors. Results: Extensive network analysis revealed a discrete OSA disease module centered on two interconnected protein kinases—CK1δ and PINK1—that mechanistically bridge circadian disruption and neurodegeneration. Among natural alkaloids, Nigellidine showed strongest CK1δ binding (−8.0 kcal/mol) and Nigellicine strongest PINK1 binding (−8.6 kcal/mol). Rationally designed dual inhibitors demonstrated superior binding: ICL (−7.2 kcal/mol PINK1, −8.9 kcal/mol CK1δ) and PFL (−10.8 kcal/mol CK1δ, −11.2 kcal/mol PINK1), representing −2.6–2.8 kcal/mol improvements over reference compounds. Conclusions: This study establishes a comorbidity-driven translational framework identifying the CK1δ-PINK1 axis as a therapeutic target in OSA. The rationally designed dual inhibitors represent third-generation precision therapeutics addressing OSA’s multi-dimensional pathophysiology, while the five-tier workflow provides a generalizable template for drug discovery in complex multimorbid diseases. Full article