Search Results (107)

Since inflammation is a fundamental process involved in tissue injury and repair, the evaluation of the anti-inflammatory potential of novel compounds is of considerable importance. Acute toxicity evaluation in Swiss albino mice revealed that the synthesized thiazolidin-4-one derivatives of ferulic acid possess moderate toxicity. The in vivo biological activity of synthesized thiazolidin-4-one derivatives (1a–j) was assessed through a model of acute inflammation induced by carrageenan in rats and in a chronic inflammation model induced in rats using the granuloma test. The compounds exhibited significant anti-inflammatory effects, with maximum activity observed 24 h after administration, suggesting a prolonged duration of action. In the acute inflammation model, compound 1g exhibited the highest anti-inflammatory activity, achieving 97.43% inhibition of inflammatory edema after 24 h. In the chronic inflammation model, all derivatives reduced granulation tissue formation, indicating inhibition of the proliferative component of inflammation, with compound 1e showing the highest inhibition (79.85%). Safety evaluation was complemented by biochemical and hematological investigations performed on blood samples collected from the experimental animals. Hepatic function was assessed by measuring serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), together with renal and hematological parameters, revealing no significant toxicity. In addition, biochemical analysis of liver homogenates demonstrated modulation of oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities, indicating that the investigated thiazolidin-4-one derivatives do not induce marked oxidative imbalance under the experimental conditions. Overall, compound 1g emerged as the most promising derivative based on its balanced anti-inflammatory efficacy and favorable oxidative stress profile. Full article

Extracellular traps (ETs) are a novel host defense mechanism used to immobilize and eliminate invading microorganisms, and their formation depends on the recognition of foreign pathogens by membrane receptors. Previous studies have demonstrated that Vibrio splendidus flagellin can induce the release of ETs in coelomocytes of the sea cucumber Apostichopus japonicus, yet the underlying regulatory mechanism remains unclear. Here, we identify another Toll-like receptor (TLR) homolog, AjTLR2, in Apostichopus japonicus, which is composed of an extracellular LRR domain, a transmembrane domain, and an intracellular TIR domain. As a membrane receptor, AjTLR2 is upregulated upon infection with Vibrio splendidus AJ01, which is isolated from diseased Apostichopus japonicus. The extracellular LRR domain exhibits binding activity toward LPS, PGN, and MAN. In addition to these ligands, AjTLR2 recognizes flagellin C of AJ01 (AJ01-FliC), whereas other AjTLRs, such as AjToll and AjTLR3, do not. Further functional analysis reveals that knockdown of AjTLR2 results in a reduction in the typical weblike DNA structures of ETs, accompanied by a significant decrease in the expression of the ET-associated antimicrobial proteins H2A, H2B, and lysozyme. Furthermore, AjTLR2 knockdown similarly inhibits ET formation induced by recombinant AJ01-FliC protein. Mechanistically, the Apostichopus japonicus proto-oncogene tyrosine-protein kinase Src homolog (AjSRC), previously identified in our laboratory, is a downstream signaling molecule of AjTLR2 and is recruited via the TIR domain of AjTLR2. Knockdown of AjSRC also suppresses AJ01-FliC-induced ET formation. Collectively, our results indicate that the recruitment of AjSRC by AjTLR2 represents a potential regulatory pathway for AJ01-FliC induced ET generation. Full article

The divalent metal transporter DMT1 (SLC11A2) is implicated in diverse human pathologies including cancers, inflammatory and degenerative diseases. Small molecules targeting this membrane protein are actively searched. Following the identification of the pyranocoumarin praeruptorin A as an inhibitor of ferroptosis that is able to bind to DMT1, we have investigated the interaction of related natural products with DMT1 using molecular modeling to determine structure-binding relationships. Two series of compounds were tested: praeruptorins A-H and qianhucoumarins A-J, all isolated previously from the roots of the Chinese medicinal plant Peucedanum praeruptorum Dunn (Bai-Hua Qian-Hu). The antitumor compound praeruptorin C was identified as the best DMT1 ligand in the series, with a binding capacity largely superior to that of praeruptorin A and also well superior to the reference organoselenium product ebselen, at least from an in silico perspective. Praeruptorin C, and to a lower extent praeruptorins F and H, can form stable complexes with DMT1 upon binding close to the ebselen binding site. Qianhucoumarins C and I were also identified as potential binders. Altogether, the analysis of the 18 natural products enabled identification of structural elements implicated in the target binding process. The curvature of the tricyclic pyranocoumarin scaffold and the angeloyl side chain at position 9 seem to contribute importantly to the protein interaction. An experimental validation is required but the docking study paves the way to the discovery and design of tricyclic coumarin derivatives targeting DMT1. Full article

Anaerobic digestion (AD) of agro-industrial residues supports the green energy transition by converting organic matter into renewable biogas. Sugar beet pulp is a highly fermentable feedstock, although its process response may vary with chemical composition. This study examined how chemical composition affects mesophilic biogas-production kinetics of sugar beet pulp prepared under laboratory conditions from surplus sugar beet roots. The roots represented ten sugar beet varieties (A–J), and the prepared pulp was characterised for pH, dry matter, organic dry matter, mineral composition, and the relative shares of simple sugars, polysaccharides, protein, and fibre. Batch digestion tests were performed at 39 °C for 30 days. Production curves were analysed using complementary kinetic models (modified Gompertz and a two-fraction first-order model) to capture the lag phase and the contributions of rapidly and slowly degradable substrate pools. Biogas yields ranged from 126 to 141 m³ Mg⁻¹ fresh matter with 50–55% CH₄, corresponding to 64.3–76.1 m³ CH₄ Mg⁻¹ organic dry matter, while organic matter conversion reached 71.2–82.4%. Varieties enriched in simple sugars exhibited a higher share of the fast-degradable fraction and shorter lag phases, indicating faster onset and stronger methane formation. In contrast, higher fibre contents reduced the slow-fraction rate constant and lowered overall conversion, consistent with hydrolysis-limited degradation of the structural carbohydrate matrix. The mineral ion background, particularly K and Na, indicated moderate ionic buffering and stable operation without inhibition. The novelty of this work lies in integrating detailed compositional profiling with dual kinetic modelling to translate chemical fingerprints into tentative process-relevant implications. These implications include feeding strategy, organic loading control and hydraulic retention time selection, and they require further validation in continuous or semi-continuous AD systems. Full article

Thiazolyl-benzene/camphor sulfonamide derivatives (series 4a–k, 5a–j and 6a–i) were synthesized by reaction of various aryl sulfonyl chlorides and camphor sulfonyl chlorides with 2-amino-4-phenylthiazole. The compounds were evaluated for antibacterial, antioxidant, and α-glucosidase/α-amylase inhibitory activities. Biological screening showed that 4h, 5g and 5i displayed significant activity against most Gram-positive bacteria (MICs 4.68–18.75 µg/mL), while 4b and 5i were active against most Gram-negative bacteria with similar MIC ranges. In the DPPH assay, 4e, 4f, 4g and 4h exhibited slightly stronger radical-scavenging activity than ascorbic acid (IC₅₀ ≈ 3.5–3.8 µM vs. 4.14 µM); 5f emerged as the best dual carbohydrate-digesting enzyme inhibitor, and 5b and 5e demonstrated selectivity toward α-amylase. Full article

Background: Diets composed of various components have been shown to influence inflammatory diseases such as asthma. While most studies have focused on fiber-rich diets to investigate their effects on the immune system and, consequently, on asthma, little is known about the impact of sugar-rich diets, particularly when such diets are consumed over short periods of time. Methods: To investigate the short-term effects of a sugar-rich diet on allergic airway inflammation, A/J mice were fed either a standard diet or a sugar-enriched diet and subsequently sensitized and challenged with ovalbumin or PBS. Airway inflammation was assessed by bronchoalveolar lavage (BAL) cell analysis, including eosinophil counts and cytokine levels (IL-4, TNF-α, IL-33), and by lung histology (H&E for inflammatory infiltrate and PAS for mucus). Serum IgE levels were also measured. In addition, glucose tolerance, visceral and subcutaneous adipose tissue mass, and inflammatory markers in visceral adipose tissue were evaluated. Results: Short-term consumption of a sugar-rich diet induced glucose intolerance and expansion of adipose tissue, particularly visceral fat, independent of ovalbumin sensitization. Gonadal adipose tissue analysis revealed a shift toward M1 macrophage polarization, characterized by elevated TNF-α, IL-6, and IL-1β, increased leptin levels, and reduced adiponectin. In OVA-sensitized mice, the sugar-rich diet significantly exacerbated eosinophil infiltration in BAL, increased IL-4, TNF-α, and IL-33, and enhanced PAS-positive mucus accumulation and inflammatory infiltrates in the lung. Moreover, total serum IgE was significantly higher in allergic mice fed the sugar-rich diet compared with allergic mice on the standard diet. Importantly, in non-sensitized mice fed the sugar-rich diet, no pulmonary inflammation was detected by BAL, demonstrating that HSD alone does not induce asthma but amplifies allergic responses when sensitization is present. Conclusions: Our findings demonstrate that short-term consumption of a sugar-rich diet is sufficient to exacerbate, but not initiate, allergic pulmonary inflammation. From a translational perspective, reducing dietary sugar intake may represent a valuable adjuvant strategy in the management of allergic asthma. Full article

The tissue regeneration of sea cucumber (Apostichopus japonicus) involves precise intercellular signal pathway transduction and gene expression regulation. This study investigated the function of the Notch signaling pathway in A. japonicus papilla regeneration and its modulation by LED light of varying intensities. We detected the expression patterns of Notch signaling pathway-related genes and their downstream cell proliferation-related genes during papilla regeneration, and further verified the pathway function via gene silencing, combined with histological analyses to explore LED-mediated effects. Gene expression assays revealed that AjNotch, AjSu(H), AjHes1, AjCyclinA, AjCyclinD and AjCDK8 were significantly upregulated at 28 days post papilla excision (p < 0.05). LED light treatment accelerated papilla regeneration in a light intensity-dependent manner, with the most pronounced promotion at 2000 lx (p < 0.05). Moreover, LED light treatment was associated with altered expression of Notch signaling pathway genes and their downstream proliferation-related genes in a light intensity-dependent manner. Gene silencing of AjNotch significantly downregulated its downstream target genes (p < 0.05), attenuated the regenerative promotion of LED light, and reduced cell proliferation rate (p < 0.05). These findings suggest that the Notch signaling pathway is pivotal for A. japonicus papilla regeneration, and LED light modulates papilla regeneration with concurrent changes in the expression of Notch pathway-related genes. This study provides novel insights into the function of the Notch signaling pathway in echinoderm regenerative development. Full article

Apostichopus japonicus undergoes evisceration in response to adverse environmental stimuli, and its coelomocytes undergo rapid regeneration within 6–24 h to restore innate immune function. FOS, an immediate early gene, regulates cell proliferation and cycle, but its role in A. japonicus coelomocyte regeneration after evisceration is unclear. In this study, AjFOSL from A. japonicus was cloned, which harbors a 609 bp open reading frame (ORF) encoding 202 amino acids (aa) with a conserved bZIP domain and is localized on chromosome 14. It shares 58% homology with FOS from Holothuria leucospilota and Lytechinus pictus. Phylogenetic analysis revealed that AjFOSL clusters closely with FOS from Magallana gigas and Mytilus edulis. Tissue distribution analysis showed that AjFOSL was widely expressed in various tissues, with the highest expression level detected in the tentacles. Temporal expression profiling demonstrated that AjFOSL was significantly upregulated by 1.75-fold at 6 h after evisceration. After AjFOSL knockdown, the peak expression of Cyclin A, Cyclin B, and E2F was delayed and the coelomocyte number was consistently reduced compared with that in the evisceration-only group. The AjFOSL acted as an immediate early response gene and was associated with the regulation of coelomocyte regeneration by modulating the expression of cell cycle-related genes. This study provides novel insights into the molecular associations underlying coelomocyte regeneration and the evolutionary adaptation of FOS genes in echinoderms. Full article

Background/Objectives: Q fever, caused by Coxiella burnetii, is typically treated with doxycycline, but its efficacy is limited in chronic cases and may be poorly tolerated. Systemic ciprofloxacin shows limited activity for acute Q fever. However, inhaled liposomal formulations may provide therapeutic benefit. Methods: Two inhaled ciprofloxacin formulations (Lipoquin^® and Apulmiq^®) were evaluated in an A/J mouse model of Q fever and compared with intraperitoneal ciprofloxacin and oral doxycycline. Initially, pharmacokinetic studies were performed to determine an appropriate dosing regimen for the inhaled ciprofloxacin formulations. A separate cohort of mice were then infected with C. burnetii and treated once daily via nebulisation with Lipoquin or Apulmiq, initiated at 24, 48, or 72 h post-challenge. Clinical signs, weight change, splenomegaly, bacterial burden, and lung histopathology were evaluated. Results: Pharmacokinetic analysis confirmed sustained lung concentrations of inhaled ciprofloxacin, supporting once-daily dosing. Inhaled Lipoquin and Apulmiq significantly reduced clinical signs, weight loss, splenomegaly, and pulmonary bacterial burden compared to untreated controls and doxycycline-treated mice. Histopathology revealed decreased lung inflammation and lesion severity following inhalational dosing. Systemic ciprofloxacin slightly reduced splenic bacterial burden but was less effective in controlling pulmonary infection. Conclusions: Inhaled liposomal ciprofloxacin demonstrated superior protection and reduced respiratory manifestations of Q fever compared to doxycycline and systemic ciprofloxacin. These findings suggest inhaled formulations may represent a viable alternative for the treatment of Q fever pneumonia. Further studies are needed to evaluate clinical applicability and long-term outcomes. Full article

A series of benzimidazole derivatives 6a–j was designed and synthesized via the condensation of the corresponding o-phenylenediamine intermediates with formic acid. Antibacterial activity was evaluated in vitro using the agar well diffusion method against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Klebsiella pneumoniae, with nitrofurantoin (300 µg/mL) as the positive control. Antifungal screening was performed against Aspergillus flavus, Penicillium duclauxii, and P. italicum at 20 and 50 µg/mL, with Amphotericin B as the reference drug at the same concentrations. Most compounds exhibited moderate to good antimicrobial activity. MIC determination identified 6h as the most active antibacterial agent (MIC = 5.0 µg/mL). The SEM analysis of bacteria treated with 6h revealed marked morphological damage, including cell deformation and membrane disruption, supporting a bactericidal mode of action. Collectively, these results highlight benzimidazole derivatives as promising scaffolds for the development of broad-spectrum antibacterial and antifungal agents. Full article

Maize silage can play a key role in policies aimed at stabilising local energy systems, as it constitutes a critical renewable feedstock for European biogas plants. By providing a dense and predictable source of chemical energy, it supports balance and reliability in the agricultural energy sector. To convert this potential into stable energy production, operators require kinetic models that translate routine silage quality indicators into concrete guidance for digester operation and control. Therefore, the aim of this article was to evaluate the batch kinetics of anaerobic digestion (AD) of maize silage and to select an adequate model for describing biochemical methane potential (BMP) profiles and associated energy recovery in the context of start-up, organic loading rate (OLR), hydraulic retention time (HRT) and feedstock preparation. Ten batches of silage (A–J) were examined, covering a realistic range of pH, electrical conductivity (EC), dry and volatile solids, ash, protein–fat–fibre fractions, fibre composition (NDF, ADF and ADL), derived fractions (hemicellulose, cellulose, and residual organic matter (OM)), C/N ratio and macro-/micronutrient profiles, including trace elements relevant to methanogenesis (Ni, Co, Mo, and Se). BMP tests were carried out in batch mode, and the resulting curves were fitted using the modified Gompertz and a first-order kinetic model. Methane yields of approx. 100–120 m³ CH₄/Mg fresh matter (FM) and 336–402 m³ CH₄/Mg volatile solids (VS), with CH₄ contents of 52–57% v/v, were typical for energy-grade maize silage. Kinetic and energetic behaviours were governed mainly by residual OM and hemicellulose (shortening the lag phase and increasing the maximum methane production rate), the ADL/cellulose ratio (controlling the slower hydrolytic tail), EC and Na/Cl/S (extending the lag phase), and C/N together with Ni/Co/Mo/Se (stabilising methanogenesis). The modified Gompertz model reproduced BMP curves with a pronounced lag phase and asymmetry more accurately (lower error and better information criterion values), and its parameters directly support start-up design, OLR ramp-up and energetic performance optimisation in bioenergy reactors. The novelty of this work lies in combining batch BMP tests, comparative kinetic modelling and detailed silage characterisation to establish quantitative links between kinetic parameters and routine maize silage quality indicators that are directly relevant for biogas plant operation and renewable energy production. Full article

Heterologous expression of silent biosynthetic gene clusters represents a key strategy for the discovery of structurally novel natural products. In this study, we obtained ten new tetronate natural products, designated as talactones A–J (1–10), through heterologous expression of a polyketide synthase–nonribosomal peptide synthetase (PKS-NRPS) gene cluster (tho) from the fungus Aspergillus flavipes LY1-5 in A. nidulans A1145. Their structures were elucidated by comprehensive HR-ESI-MS and NMR analyses. Notably, talactone A (1) contains a rare 1,4-thiazepane scaffold, whereas talactones B (2) and C (3) feature a novel 2,3-dihydrofuro [3,4-b]pyridine-4,5(1H,7H)-dione skeleton. Biosynthetic investigations indicate that the 1,4-thiazepane ring in 1 arises from a non-enzymatic reaction between a tetronate acid and cysteine, while 2 and 3 are derived from 5 and 6, respectively, via spontaneous intramolecular cyclization under acidic conditions. Antibacterial activity assays revealed that compounds 1–3, 9, and 10 exhibit moderate antibacterial effects. Full article

Gray mold caused by Botrytis cinerea poses a major threat to tomato production worldwide. This study investigated the antifungal efficacy and defense-inducing potential of Agricultural Jiaosu (AJ), a fermented bioproduct derived from agricultural residues. In vitro, AJ exhibited strong inhibitory activity against B. cinerea (IC₅₀ = 3.9%), primarily through acidic metabolites (pH < 4.2) that disrupted fungal membranes and suppressed antioxidant enzymes, while later-stage inhibition was maintained by Acetobacter populations (6.7 × 10⁷ copies μL⁻¹) through competition for nutrients. In vivo, foliar application of 0.5% AJ significantly promoted tomato growth and enhanced resistance by stimulating antioxidant (SOD, CAT, POD) and defense-related (PAL, PPO) enzyme activities, reducing oxidative damage and lowering gray mold incidence by 55%. Collectively, AJ exerts a dual mode of action that combines direct pathogen suppression with activation of host systemic resistance. These results highlight AJ as a sustainable, residue-free biocontrol solution that offers an environmentally friendly alternative to chemical fungicides for effective management of gray mold in tomato cultivation. Full article

The development of grapevine varieties combining powdery mildew (Erysiphe necator) resistance with acceptable wine quality represents an important goal for sustainable viticulture. This study evaluated the oenological potential of five advanced breeding lines carrying Run1 or Run1Ren1 resistance loci, developed through marker-assisted selection to achieve 99.2–99.6% Vitis vinifera genome content. Genotypes were assessed under Chilean conditions during the 2024–2025 seasons, analyzing disease resistance, berry characteristics, and wine chemical parameters. All resistant genotypes exhibited complete powdery mildew resistance (OIV scores 9) without fungicide applications. Wine analyses showed pH 3.4–3.9, titratable acidity 3.7–7.8 g/L, and total phenolics 229.2–1356.1 mg GAE/L, values within ranges reported in the literature for commercial wines. Two genotypes evaluated across both seasons showed different patterns of year-to-year variation, with AJ-T2 showing 4.7% variation in anthocyanin content, while AJ-T6 exhibited greater variation in phenolic parameters. HPLC analysis revealed anthocyanin profiles dominated by malvidin-3-glucoside without diglucoside forms, consistent with V. vinifera patterns. These preliminary results from single-plant evaluations suggest that marker-assisted breeding may contribute to developing disease-resistant varieties with wine chemical parameters within commercial ranges, though multi-plant trials with appropriate controls are essential for validation. Full article

This study aimed to develop polylactic acid (PLA)-based membranes incorporating tramadol (TMD) using air jet spinning (AJS), ensuring stable physicochemical properties and biocompatibility. Two groups were fabricated: 10% PLA membranes (control) and 10% PLA membranes loaded with TMD in an 80:1 ratio (experimental). Characterization included scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-VIS), and biocompatibility assays with human osteoblasts using resazurin, crystal violet staining, and 5-chloromethylfluorescein diacetate for fluorescence microscopy. SEM revealed a homogeneous, randomly distributed fiber pattern, with diameters under 5 µm and no structural voids. DSC and TGA indicated that TMD was uniformly incorporated, increased the thermal capacity, and slightly lowered the onset and inflection degradation temperatures. FT-IR confirmed the chemical compatibility of TMD with PLA, showing no structural alterations. UV-VIS detected sustained TMD release over 72 h. Biocompatibility tests showed no cytotoxic effects; cell viability and proliferation in TMD-loaded membranes were comparable to controls. Statistical analysis used ANOVA and Wilcoxon tests. 10% PLA membranes loaded with TMD at an 80:1 ratio exhibited stable physicochemical characteristics and favorable biocompatibility, supporting their potential use in drug delivery systems. Full article