Search Results (449)

This study presents the synthesis and electrochemical characterization of meso-tetracyanobutadiene (TCBD)-functionalized diphenylporphyrin (DPP) complexes incorporating copper (Cu) and nickel (Ni) metals. These push–pull metallo diphenylporphyrin–TCBD complexes were synthesized via a [2 + 2] cycloaddition–retroelectrocyclization reaction between 5-bromo-15-formyl-10,20-diphenylporphyrin metal(II) complexes (M = Cu, Ni) and tributyl(phenylethynyl)stannate, followed by tetracyanoethylene (TCNE) addition. The resulting TCBD-functionalized porphyrins were obtained in moderate yields (70–75%) and thoroughly characterized by ¹H and ¹³C NMR, UV-Vis spectroscopy, MALDI-TOF-MS, and single-crystal XRD. Although the single-crystal X-ray structure of NiDPP was solved, DFT calculations were used to determine the structures of the donor–acceptor MDPP-TCBD systems and to visualize their electronic structures. HOMO on the porphyrin π system and LUMO on the TCBD entity were observed, and energy level diagrams clearly laid out the electron donor and acceptor parts of the molecular systems. As expected, these novel donor–acceptor porphyrinoid assemblies exhibited enhanced push–pull properties in both the ground and excited states. Femtosecond transient absorption studies revealed that both NiDPP-TCBD and CuDPP-TCBD populate the charge-transfer state upon photoexcitation, with lifetimes of 383.1 ps and 484.7 ps, respectively, in benzonitrile. The charge-transfer states populated the triplet or doublet states (in the case of CuDPP) before returning to the ground state. Full article

Background: In this study, we aimed to compare metabolomic profiles, biodistribution, and detoxification patterns of the novel SN-38 derivative NMe with irinotecan (IR), and to identify NMe-specific metabolites to evaluate its preclinical pharmacokinetic advantages. Methods: In vivo ADME studies were conducted for NMe, a 9-aminomethyl SN-38 derivative, and IR following a single intraperitoneal dose of 40 mg/kg in mice. Additionally, ADMET properties were predicted using ADMETlab and SwissADME tools for comparison. Levels of NMe and irinotecan absorbed into plasma, distributed to tissues, and metabolized were monitored in liver, lung, spleen, kidney, and stool samples at 15, 30, and 60 min post-administration. Tissue extracts were analysed using high-performance liquid chromatography (HPLC), liquid chromatography–electrospray ionization quadrupole time-of-flight-tandem mass spectrometry (LC-ESI-QTOF-MS), and nuclear magnetic resonance (NMR) techniques after lyophilization and reconstitution. We compared the metabolomic profiles of irinotecan and NMe. Results: We identified and confirmed NMe-specific metabolites, including 9-CH₂-S-cysteine conjugate, 9-CH₂OH, and NMe-formyl. Notably, novel irinotecan metabolites (IR-OH and IR-ΔE) were detected in small amounts in kidney samples. In some cases, two literature-known photodegradation products of irinotecan were present. NMe was found to quickly metabolize with different distribution to tissues, significantly greater to kidney and liver. Two SN-38 glucuronides, SN-38G(α) and SN-38G(β), were detected corresponding to α- and β-anomers. Where it was possible, NMe, IR and SN-38 were quantified using external calibration curves. In IR group, controlled and prolonged release of SN-38 was confirmed in all samples, yet SN-38G was observed in minority only in plasma, kidney, or lungs. In NMe groups, great relative amounts of SN-38 and SN-38G were detected. Greater content of SN-38G in NMe group than in irinotecan is expected to contribute to modulation and alleviation of some side effects in irinotecan-involved therapies, such as gastrointestinal toxicities (GIT). Conclusions: NMe shows a distinct metabolic profile characterized by rapid biotransformation, higher systemic glucuronidation of SN-38, and formation of unique metabolites, suggesting a potentially wider therapeutic window and reduced toxicity compared with IR. Full article

Oxidative stress is a key driver of chronic inflammatory diseases. Anodendron affine is a native Formosan plant species in Taiwan that remains largely underexplored phytochemically and bioactivity. To reveal the bioactive constituents and assess its potential as a source of anti-inflammatory antioxidants, we performed bioactivity-guided fractionation and evaluated the inhibition of superoxide anion (O₂^•−) generation in formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated human neutrophils. Molecular docking simulations were employed to model interactions with Formyl peptide receptor 1 (FPR1) and the Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, including neutrophil cytosol factor 1 (p47phox) and NADPH oxidase 2 (NOX2), to propose a theoretical mechanism of action. Phytochemical investigation led to the isolation of two new compounds, methyl 4,5-O-diferuloyl-3-methoxyquinate (1) and 16-pregnen-3,12,20-trione (2), together with four known compounds. Notably, 4-hydroxy-3-prenylbenzoic acid (5) exhibited potent inhibitory activity (IC₅₀ = 17.65 ± 0.97 μM), surpassing the activity of the positive control, ibuprofen (IC₅₀ = 27.85 ± 3.56 μM). Docking studies suggested that anodendrosin H (4) and 4-hydroxy-3-prenylbenzoic acid (5) exhibit high predicted binding affinity to p47phox and NOX2. Based on these results, compounds 1, 4, and 5 from A. affine were identified as potential lead candidates for the development of novel anti-inflammatory therapeutics. Full article

Objectives: Periodontitis is a multifactorial inflammatory disease initiated by pathogenic bacteria, such as Porphyromonas gingivalis. Resolvin D1 (RvD1) plays a pivotal role in inflammation resolution. This study aimed to identify the mechanism of the regulatory effects of RvD1 on the inflammatory response of human periodontal ligament cells (hPDLCs). Methods: To investigate the mechanism of RvD1’s impact on the hPDLCs, RNA-sequencing (RNA-seq) was used and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to assess the signaling pathways in which NF-κB and MAPK were determined to play a significant role. Alterations in NF-κB and MAPK pathways were verified by immunofluorescence (IF), quantitative real-time PCR (qRT-PCR), and Western blotting (WB). The expression of RvD1 and lipoxin A4/formyl peptide receptor 2 (ALX/FPR2) was assessed by IF and WB. Inflammatory cytokine interleukin (IL) 6 and IL-1β release was measured by ELISA. Results: GO and KEGG analyses indicated that RvD1 regulates the inflammatory process in PDLCs primarily via TLR4-MyD88-mediated NF-κB and MAPK signaling. RvD1 suppressed lipopolysaccharide (LPS)-induced TLR4 and MyD88 expression, inhibited phosphorylation of NF-κB p65 and its inhibitor IKBKB, and attenuated phosphorylation of p38 MAPK, ERK, and JNK. ALX/FPR2 was expressed on hPDLCs and was further upregulated upon treatment with RvD1. RvD1 significantly down-regulated the IL-6 and IL-1β levels in LPS-stimulated hPDLCs. Conclusions: RvD1 regulates the inflammatory response of LPS-stimulated hPDLCs by the TLR4-MyD88-MAPK and TLR4-MyD88-NF-κB signaling pathways, suggesting the potential role of RvD1 in restoring periodontal tissue homeostasis by regulating PDLC response to inflammatory and infectious stimuli. Full article

The first representative of the aziridine-fused benzo[e][1,4]thiazine series was synthesized from methyl 2-bromo-2-phenyl-2H-azirine-2-carboxylate and benzo[d]thiazole in 74% yield. The reaction proceeds via the S_N2′-S_N2′-cascade to form the azirinylthiazolium salt followed by a water-induced thiazole ring expansion. The structure of the title compound was established based on ¹H, ¹³C, 2D NMR spectroscopy and high-resolution mass spectrometry, and unambiguously confirmed by X-ray diffraction analysis. Full article

2,5-furandicarboxylic acid (FDCA), a high-value biomass-derived monomer, serves as a crucial building block for sustainable polymers including polyesters, polyamides, and polyurethanes. This study systematically investigated the catalytic oxidation of 5-hydroxymethylfurfural (HMF) to FDCA over Pt/Al₂O₃ and Pt–Bi/Al₂O₃ catalysts. The 5Pt/Al₂O₃ catalyst yielded 60.6% FDCA after 12 h under optimized conditions (80 °C, 0.1 MPa O₂, 1 equiv. Na₂CO₃). Remarkably, Bi-modified 5Pt–1Bi/Al₂O₃ catalyst dramatically enhanced catalytic performance, achieving 94.1% FDCA yield within 6 h under optimized conditions (80 °C, 1.5 MPa O₂, 2 equiv. Na₂CO₃). Comprehensive characterization revealed that the exceptional activity originates from Bi–O–Pt interactions that modulate the electronic structure and oxidation state of Pt active sites, which facilitates the oxidation of intermediate 5-formyl-2-furancarboxylic acid (FFCA) to FDCA, the rate-limiting step of HMF oxidation. This work demonstrates an efficient Bi-promoted Pt catalytic system for FDCA production with significant potential for industrial application. Full article

This bioinformatic study provides a comprehensive theoretical assessment of oxalate-degrading enzymes in probiotics. Kidney stone disease is a common urological disorder with rising global incidence, largely driven by the precipitation of insoluble calcium oxalate salts. Current treatments—including thiazides, lithotripsy, or ultrasound fragmentation—often show variable outcomes and high recurrence rates. Here, we systematically assessed the oxalate-degrading potential of 38 probiotic species listed in the List of Cultures Available in Food (China National Health Commission) along with selected next-generation probiotics. Using BLASTp homology searches, we identified seven strains carrying both oxalyl-CoA decarboxylase (OXC) and formyl-CoA transferase (FRC) genes, one encoding oxalate decarboxylase (OXDC), and three harboring subunits of oxalate oxidoreductase (OOR). Additionally, seven species from international probiotic lists (EFSA QPS and AEProbio) were analyzed, among which two carry both OXC and FRC genes. We prioritized strains with the coupled OXC-FRC pathway or OOR enzymes, examined catalytic site conservation by multiple sequence alignment, and performed AlphaFold-based structural prediction with Template Modeling (TM)-align scoring. Species with TM-scores >0.8 exhibited highly conserved folds, suggesting functional oxalate degradation capacity. These findings provide theoretical guidance for identifying probiotic candidates with oxalate-degrading activity and establish a framework for developing next-generation functional probiotics to alleviate kidney stone disease. Full article

Vascular health relies on the proper function of endothelial cells, which regulate vascular tone, blood fluidity, and barrier integrity. Endothelial dysfunction, often aggravated by inadequate vitamin absorption, contributes to a spectrum of clinical disorders, including cardiovascular disease, cerebrovascular disease, peripheral artery disease, age-related macular degeneration, lymphedema, and chronic venous insufficiency. B-group vitamins (especially folate, or vitamin B9), along with vitamins B12, B6, C, D, and E, are essential in maintaining endothelial function, supporting DNA synthesis, regulating methylation, enhancing cellular repair, mitigating oxidative stress and inflammatory signaling, and curtailing vascular damage. Folate is noted for its central function in one-carbon metabolism and in converting homocysteine to methionine, thereby reducing vascular toxicity. We cover natural dietary sources of folate, synthetic folic acid, and the biologically active forms 5-methyl-(6S)-tetrahydrofolate (L-5-MTHF, L-methylfolate) and 5-formyl-(6S)-tetrahydrofolate (levoleucovorin). Therapeutic strategies to address vascular health and prevent hyperhomocysteinemia in order to preclude follow-on disorders include targeted vitamin supplementation, dietary improvements to ensure a sufficient intake of bioavailable nutrient forms, and, in certain clinical contexts, the use of active L-methylfolate or levoleucovorin (a drug product) to bypass metabolic conversion issues. These evidence-based interventions aim to restore endothelial homeostasis, slow disease progression, and improve patient outcomes across a variety of disorders linked to poor vascular health. Full article

Pd nanoparticles (Pd/SiC) with a main exposed plane of Pd (111) were prepared by liquid phase reduction. The use of formaldehyde as a methylation reagent for the photocatalytic methylation of aromatic nitro compounds to N,N-methylaniline resulted in one-pot methylations of aromatic nitro compounds with high photocatalytic activity and selectivity under mild reaction conditions. The high catalytic activity of Pd/SiC in N-methylation reactions arises from the Mott–Schottky contact between Pd and SiC, which promotes the transfer of photogenerated electrons to Pd. The high selectivity is ascribed to the ability of Pd nanoparticles to catalyze the hydrogenation of nitro groups to amino groups, which subsequently undergo direct methylation with formaldehyde, bypassing the intermediate formylation step. Full article

Pain is a multifactorial phenomenon involving neuronal, immune, and glial components. Annexin A1 (AnxA1), a glucocorticoid-regulated protein with pro-resolving properties, has emerged as a critical modulator of pain. Present in both peripheral and central compartments, AnxA1 acts through the formyl peptide receptor FPR2/ALX to regulate immune responses, modulate nociceptive signaling, and promote tissue homeostasis. Its mimetic peptide, Ac_2–26, has demonstrated robust antinociceptive effects in various pain models, including those induced by inflammation, tissue injury, viral infection, and opioid exposure. AnxA1 modulates cytokine expression, inhibits pro-nociceptive pathways such as TRPV1 and CXCL12/CXCR4, and reprograms macrophages. In the central nervous system, it attenuates neuroinflammation and central sensitization. Notably, AnxA1 can exhibit context-dependent effects, contributing to either the resolution or exacerbation of inflammation. This review examines the molecular mechanisms by which AnxA1 bridges the immune and nervous system pathways, highlighting its therapeutic potential in pain management. Full article

Commercial fruit juices are categorized into juice not from concentrate (JNFC) and juice from concentrate (JFC). Tomato juice is one of the most popular vegetable juices, and its aroma is an important factor in evaluating its quality. However, differences in the aroma characteristics of JNFC and JFC tomato juices have not been clearly identified. This study aimed to investigate the volatile organic compounds (VOCs) involved in distinguishing between JNFC and JFC using commercially available tomato juices. Furthermore, the effect of concentration on the VOC composition was evaluated using different procedures. Twenty-three commercial tomato juices were prepared for analysis of VOCs using headspace solid phase microextraction-gas chromatography mass spectrometry (HS-SPME-GC-MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to discriminate the samples into JNFC and JFC groups. JNFC contained 43 VOCs, which was more than twice that contained in JFC, and the quantitative variation was larger in JNFC than in JFC. In particular, the JNFC group contained significantly more alcohol and phenol compounds. On the other hand, the JFC group contained more formyl pyrrole and Strecker aldehydes. Additional GC-MS/olfactometry (GC-MS/O) and odor active value analyses indicated that (Z)-3-hexenol and 3-methylbutanal were the best VOCs to distinguish between the JNFC and JFC groups. Furthermore, different concentration procedures, including heating concentration (HC), decompression concentration (DC), and freeze drying (FD), were performed, and the corresponding VOCs were compared. HC and DC reduced the levels of most of the compounds to the levels seen in commercial JFC. These results indicate that the concentration procedure is an important processing stage, in addition to the break process, that determines the quality of tomato juice. Full article

Crotoxin (CTX), the main toxin in Crotalus durissus terrificus venom, is a heterodimeric complex known for its antitumoral, anti-inflammatory, and immunomodulatory properties. In macrophages, CTX stimulates energy metabolism, pro-inflammatory cytokines, superoxide production, and lipoxin A₄ secretion while inhibiting macrophage spreading and phagocytosis. These effects are completely blocked by Boc-2, a selective formyl peptide receptors (FPRs) antagonist. Despite the correlation between FPRs and CTX-mediated effects, their involvement in mediating CTX entry into macrophages remains unclear. This study aimed to investigate the involvement of FPRs in CTX entry into monocytes and macrophages. For this, THP-1 cells were silenced for FPRs or treated with Boc-2. Results demonstrated that FPR-related signaling pathways, which influence macrophage functions such as ROS release, phagocytosis, and spreading, were reduced in FPR-silenced cells. However, even in the absence of FPRs, CTX was efficiently internalized by macrophages. These findings suggest that FPRs are essential for the immunomodulatory effects of CTX, but are not involved in CTX internalization. Full article

In this study, we synthesized novel donor–π–acceptor (D–π–A) functional dyes bearing a carbonyl-bridged bithiophene as a π-conjugated spacer and evaluated the absorption and fluorescence properties as well as the photostability. The developed dyes 1-CO–3-CO possess an N,N-diphenylaminophenyl electron donor unit and an electron acceptor unit such as a formyl group (1-CO), an (N,N-diethylthiobarbituryl)methylene moiety (2-CO), or a (3-dicyanomethylidene-1-indanon-2-yl)methylene moiety (3-CO). The absorption spectra of 1-CO–3-CO in dichloromethane at room temperature showed absorption maxima at 569 nm, 631 nm, and 667 nm, respectively, and the stronger acceptors in 2-CO and 3-CO led to enhancement of the ICT character. In addition, 2-CO and 3-CO had a second absorption band in the visible region, showing panchromatic absorption properties. Electrochemical analyses of the developed dyes revealed that the carbonyl bridging group in the π-spacer contributes to stabilization of the frontier orbitals such as the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO, respectively), in comparison with the referential dyes bearing a dibutylmethylene-bridged bithiophene spacer, 1-CBu₂–3-CBu₂. The HOMO/LUMO stabilization brought about high photostability in the doped poly(methyl methacrylate) film. Full article

Estradiol (E2) plays an important role in cell proliferation and certain brain functions. To reveal its mechanism of action, its detectability is essential. Only a few fluorescent-labeled hormonally active E2s exist in the literature, and their mechanism of action usually remains unclear. It would be of particular interest to develop novel labeled estradiol derivatives with retained biological activity and improved optical properties. Due to their superior optical characteristics, aza-BODIPY dyes are frequently used labeling agents in biomedical applications. E2 was labeled with the aza-BODIPY dye at its phenolic hydroxy function via an alkyl linker and a triazole coupling moiety. The estrogenic activity of the newly synthesized fluorescent conjugate was evaluated via transcriptional luciferase assay. Docking calculations were performed for the classical and alternative binding sites (CBS and ABS) of human estrogen receptor α. The terminal alkyne function was introduced into the tetraphenyl aza-BODIPY core via selective formylation, oxidation, and subsequent amidation with propargyl amine. The conjugation was achieved via Cu(I)-catalyzed azide–alkyne click reaction of the aza-BODIPY-alkyne with the 3-O-(4-azidobut-1-yl) derivative of E2. The labeled estrogen induced a dose-dependent transcriptional activity of human estrogen receptor α with a submicromolar EC₅₀ value. Docking calculations revealed that the steroid part has a perfect overlap with E2 in ABS. In CBS, however, a head-tail binding deviation was observed. A facile, fluorescent labeling methodology has been elaborated for the development of a novel red-emitting E2 conjugate with substantial estrogenic activity. Docking experiments uncovered the binding mode of the conjugate in both ABS and CBS. Full article