Search Results (208)

In this study, COOH-functionalized co-polymer of acrylonitrile and itaconic acid (P(AN-co-IA)) is synthesized via free radical copolymerization using DMSO as solvent. The continuous non-aligned carbon nanofibers (CNFs) with different amounts of metallocene (zirconocene and ferrocene) are fabricated through electrospinning, followed by a series of heat treatments under an inert atmosphere. The influence of metallocenes on electrospun carbon nanofiber diameter, alignment, and structural ordering was systematically investigated using FESEM, XRD, Raman spectroscopy, and TEM. Incorporation of dual metallocenes significantly alters the fiber diameter, improves orientation, and promotes graphitic domain formation at 1100 °C, a much lower temperature than conventional graphitization. The optimized sample (Zr-Fe)₁-P(AN-co-IA)-eGNF) exhibited the lowest I_D/I_G ratio compared to pristine and all prepared samples, indicating an improved degree of graphitization due to the uniform distribution of metallocene nanofiber matrix. Furthermore, the electrical conductivity of optimized (Zr-Fe)₁-P(AN-co-IA)-eGNF reached the highest value (1654.5 S/m) due to the high degree of graphitization of carbon nanofibers. These results show that integrating dual metallocene is an efficient pathway for tailoring nanofiber morphology and achieving conductive, structurally ordered electrospun eGNFs at reduced temperatures, with potential applications in various fields. Full article

A chemical platform for post-polymerization methods was developed, starting from the ecodesign and enzymatic synthesis of safe and sustainable bio-based polyesters containing discrete units of itaconic acid. This unsaturated bio-based monomer enables the covalent linkage of molecules that can impart desired properties such as hydrophilicity, flexibility, permeability, or affinity for biological targets. Molecular descriptor-based computational methods, which are generally used for modeling the pharmacokinetic properties of drugs (ADME), were employed to predict in silico the hydrophobicity (LogP), permeability, and flexibility of virtual terpolymers composed of different polyols (1,4-butanediol, glycerol, 1,3-propanediol, and 1,2-ethanediol) with adipic acid and itaconic acid. Itaconic acid, with its reactive vinyl group, acts as a chemical platform for various post-polymerization functionalizations. Poly(glycerol adipate itaconate) was selected because of its higher hydrophilicity and synthetized via solvent-free enzymatic polycondensation at 50 °C to prevent the isomerization or crosslinking of itaconic acid. The ecotoxicity and marine biodegradability of the resulting oligoester were assessed experimentally in order to verify its compliance with safety and sustainability criteria. Finally, the viability of the covalent linkage of biomolecules via Michael addition to the vinyl pendant of the oligoesters was verified using four molecules bearing thiol and amine nucleophilic groups: N-acetylcysteine, N-Ac-Phe-ε-Lys-OtBu, Lys-Lys-Lys, and glucosamine. Full article

The growing demand for sustainable packaging materials highlights the need for bio-based alternatives to fossil-derived polymers, particularly in barrier applications where reduced environmental impact and recyclability are critical. Poly(lactic acid) is a promising candidate due to its renewable origin and biodegradability, yet its application in aqueous dispersion coatings remains underdeveloped. In this study, copolymers were synthesized from L-(+)-lactic acid, itaconic acid, and 1,4-/2,3-butanediol via polycondensation, and a solvent-free thermomechanical method was used to prepare aqueous dispersions from the produced copolymers. The main objective of this study was to identify an optimal composition for the copolymer and dispersion to achieve small and uniformly sized dispersion particles while also assessing the scalability of the process from laboratory to pilot production. The smallest dispersion particles and most uniform size distribution were achieved with a copolymer that had an M_n close to the average (10,180 g mol⁻¹) and a low T_g (−1.4 °C). The grade and dosage of the dispersion stabilizer significantly influenced the particle size and particle size distribution. The process scale-up, including polymer production at pilot scale and dispersion preparation at bench scale, was successfully demonstrated. The water vapor barrier properties of the coated dispersions were promising (<10 g/m² at 23 °C/50% RH), supporting the potential of aqueous PLA-based dispersions as sustainable barrier coatings. Full article

A group of renewable, unsaturated resins from itaconic acid, 1,8-octanediol, and succinic anhydride were synthesized in a non-solvent and non-catalyst melt polycondensation reaction. The study addresses the need for sustainable polymeric materials suitable for additive manufacturing by investigating the influence of synthesis parameters—namely itaconic acid content, reaction time, and temperature—on the properties of poly(octamethylene itaconate-co-succinate) (POItcSc). The Box-Behnken mathematical planning method was applied to optimize the reaction conditions. The optimal synthesis conditions of POItcSc were achieved with an itaconic acid molar fraction = 0.50:0.50, reaction time t = 7 h, and reaction temperature T = 150 °C. The conversion of the carboxyl group (by titration) was 83.3%, and the maintenance of C=C bonds (by NMR) was 88.7%. Structural characterization confirmed the formation of the desired polymer through FTIR and ¹H NMR analyses. Molecular weight (M_n = 1001 g/mol for an optimal product), thermal behavior (DSC, TG, DTG), and rheological properties (η = 14.4 and 3.6 Pa∙s for an optimal product at 25 and 36.6 °C) were systematically evaluated. The synthesized POItcSc resins were transparent and exhibited physicochemical properties favorable for extrusion-based 3D printing techniques such as Direct Ink Writing, offering a promising alternative to conventional petrochemical-based inks. Full article

The recently identified proton-activated chloride (PAC) channel is ubiquitously expressed, and it regulates several proton-sensitive physiological and pathophysiological processes. While the PAC channel is activated by strong acids due to the binding of protons to extracellular binding sites, here, we describe the way in which weak acids inhibit the PAC channel by a mechanism involving a distinct extracellular binding site. Whole-cell patch clamp was performed on wildtype HEK293T cells, PAC-knockout HEK293 cells expressing human (h)PAC mutant constructs, and on hiPSC-derived cardiomyocytes. Proton-induced cytotoxicity was examined in HEK293T cells. Acetic acid inhibited endogenous PAC channels in HEK 293T cells in a reversible, concentration-dependent, and pH-dependent manner. The inhibition of PAC channels was also induced by lactic acid, propionic acid, itaconic acid, and β-hydroxybutyrate. Weak acids also inhibited recombinant wildtype hPAC channels and PAC-like currents in hiPSC-derived cardiomyocytes. Replacement of the extracellular arginine 93 by an alanine (hPAC–Arg93Ala) strongly reduced the inhibition by some weak acids, including arachidonic acid. Although lactic acid inhibited PAC, it did not reduce the proton-induced cytotoxicity examined in wildtype HEK 293 cells. To conclude, weak acids inhibit PAC via an extracellular mechanism involving Arg93. These data warrant further investigations into the regulation of the PAC channel by endogenous weak acids. Full article

This article reviews the multifaceted roles of itaconate in immune regulation and inflammatory metabolism. Itaconic acid is a dicarboxylic acid with anti-inflammatory, antioxidant, and anti-tumor properties. It is initially produced by the heating decomposition of citric acid and is closely related to the tricarboxylic acid cycle. In immune regulation, itaconate regulates macrophage function through a variety of mechanisms, including metabolic reprogramming, polarization regulation, inhibition of cytokine production, and regulation of oxidative stress. It can also affect the function of T cells and B cells. In terms of inflammatory metabolism, itaconate can regulate the production of inflammatory factors, inhibit the activity of succinate dehydrogenase, and affect cellular energy metabolism and lipid metabolism. Its mechanism of action involves the inhibition of succinate dehydrogenase, covalent modification of proteins, influence on epigenetic modification, and playing a role through the G protein-coupled receptor OXGR1 (Oxoglutarate Receptor 1). Itaconic acid derivatives have shown good effects in anti-inflammation and anti-oxidation and have broad application prospects in clinical treatment, including the treatment of inflammatory diseases, anti-tumor and anti-microbial infection. However, the long-term safety and side effects of itaconic acid as a therapeutic agent still need to be further studied. Future studies will further explore the synthesis and function of itaconic acid in different cell types, its physiological effects in non-inflammatory conditions, and its potential application in clinical treatment in order to develop new therapeutic strategies and improve the treatment effect of chronic inflammatory and metabolism-related diseases. Full article

Equine asthma is a chronic respiratory disease characterised by neutrophilic inflammation, airway hyperresponsiveness, and impaired pulmonary function. Obesity, increasingly prevalent among domestic horses, has been identified as a potential risk factor for exacerbating inflammatory conditions. This study aimed to explore whether obesity modifies neutrophil metabolism and inflammatory responses in horses affected by asthma. Six asthmatic horses in clinical remission were categorised into two groups: obese and non-obese, based on body condition score. Serum levels of interleukin-1β (IL-1β) and peripheral blood neutrophil counts were significantly higher in obese horses, indicating a heightened systemic inflammatory state. Neutrophils from obese horses displayed a stronger oxidative burst following zymosan stimulation and elevated IL-1β gene expression in response to lipopolysaccharide, suggesting a hyperinflammatory phenotype. Metabolomic profiling of neutrophils identified 139 metabolites, with notable differences in fatty acids, branched-chain amino acids, and tricarboxylic acid (TCA) cycle intermediates. Pathway enrichment analysis revealed significant alterations in fatty acid biosynthesis, amino acid metabolism, and glutathione-related pathways. Elevated levels of itaconate, citraconic acid, and citrate in obese horses indicate profound metabolic reprogramming within neutrophils. These results suggest that obesity promotes a distinct neutrophil phenotype marked by increased metabolic activity and heightened responsiveness to inflammatory stimuli. This altered profile may contribute to the persistence or worsening of airway inflammation in asthmatic horses. The findings underscore the importance of addressing obesity in the clinical management of equine asthma and open avenues for further research into metabolic-targeted therapies in veterinary medicine. Full article

Stimuli-responsive polymers (SRPs) have garnered significant attention in recent decades due to their immense potential in biomedical and environmental applications. When these SRPs are grafted onto magnetic nanoparticles, they form multifunctional nanocomposites capable of various complex applications, such as targeted drug delivery, advanced separations, and magnetic resonance imaging. In this study, we employed a one-step hydrothermal method using 3-aminopropyltrimethoxysilane (APTES) to synthesize APTES-modified Fe₃O₄ nanoparticles (APTES@Fe₃O₄) featuring reactive terminal amine groups. Subsequently, via two consecutive surface-initiated atom transfer radical polymerizations (SI-ATRP), pH- and temperature-responsive polymer blocks were grown from the Fe₃O₄ surface, resulting in the formation of poly(itaconic acid)-block-poly(N-isopropyl acrylamide) (PIA-b-PNIPAM)-grafted nanomagnetic particles (PIA-b-PNIPAM@Fe₃O₄). To confirm the chemical composition and assess how the particle morphology and size distribution of these SRP-based nanocomposites change in response to ambient pH and temperature stimuli, various characterization techniques were employed, including transmission electron microscopy, differential light scattering, and Fourier transform infrared spectroscopy. The results indicated successful synthesis, with PIA-b-PNIPAM@Fe₃O₄ demonstrating sensitivity to both temperature and pH. Full article

Despite its broad application due to its affordability, biodegradability, and natural antimicrobial and antioxidant activities, chitosan (CS) still exhibits limitations in mechanical strength and barrier effectiveness. Owing to its unique chemical characteristics, itaconic acid (IT) presents potential as a compatibilizing agent in polymeric blend formulations. Biodegradable polymers composed of chitosan (CS), itaconic acid (IT), and starch (S) were synthesized using two polymerization methods. The first method involved grafting IT onto CS at varying ratios of IT (4%, 6%, and 8% wt.), using 1% v/v acetic acid/water as the solvent and potassium persulfate as the initiator. In the second approach, starch (S) was blended with the copolymer P(CS-g-IT) at concentrations of 1%, 3%, and 5%, utilizing water as the solvent and glacial acetic acid as a catalyst. The resulting biodegradable films underwent characterization through FTIR, TGA, SEM, and mechanical property analysis. To further explore the effects of combining IT, starch, and carbon black, the blends, referred to as P[(CS-g-IT)-b-S], were also loaded with carbon black. This allowed for the evaluation of the materials’ physicomechanical properties, such as viscosity, tensile strength, elongation, and contact angle. The findings demonstrated that the presence of IT, starch, and carbon black collectively improved the films’ mechanical performance, physical traits, and biodegradability. Among the samples, the blended copolymer with 1% starch exhibited the highest mechanical properties, followed by the grafted copolymer with 8% IT and the blended copolymer mixed with carbon black at 7%. In contrast, the blended copolymer with 5% starch showed the highest hydrophilicity and the shortest degradation time compared to the grafted copolymer with 8% IT and the blended copolymer mixed with 7% carbon black. Full article

Recently, marketing authorizations were granted by the Federal Drug Administration (FDA) for pegcetacoplan and avacincaptad pegol, which inhibit C3 and C5 complement components, respectively. These two drugs were demonstrated to slow down the growth of atrophic areas in the retina. These authorizations represent a huge breakthrough for patients suffering from geographic atrophy (GA), the late stage of the dry form of Age-related Macular Degeneration (AMD). Until then, no treatment was available to treat this blinding disease. However, these two new compounds inhibiting the complement system are still not available for patients outside of the United States, and they are not devoid of drawbacks, including a poor effect on vision improvement, an increased risk of occurrence of the neovascular form of AMD and the burden of patients receiving recurrent intravitreal injections. Thus, the important medical need posed by GA remains incompletely answered, and new therapeutic options with alternative modes of action are still required. Oxidative stress and inflammation are two major potential targets to limit the progression of atrophic retinal lesions. Dimethyl fumarate, dimethyl itaconate and other activators of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) display antioxidants and immunomodulatory properties that have shown evidence of efficacy in in vitro and in vivo models of dry AMD. Tecfidera^®, whose active principle is dimethyl fumarate, is already commercialized for the treatment of autoimmune diseases such as multiple sclerosis and psoriasis. The aim of this review is to present the rationale and the design of the clinical trial we initiated to test the effectiveness and safety of repurposing Tecfidera^®, which could represent a new therapeutic alternative in patients with the dry form of AMD. Full article

Global warming poses a significant threat to lake ecosystems, with high-mountain lakes being among the earliest and most severely impacted. However, the processes affecting water ecology under climate change remain poorly understood. This study investigates, for the first time, the effects of regional warming on three high-mountain lakes, Sulzata, Okoto and Bubreka, located in the Rila Mountains, Bulgaria, by examining shifts in bacterial metabolic capacity in relation to the rate and range of utilizable carbon sources using the Biolog EcoPlate™ assay. Over the last decade, ice-free water temperatures in the lakes have risen by an average of 2.6 °C, leading to increased nutrient concentrations and enhanced primary productivity, particularly in the shallowest lake. Bacterial communities responded to these changes by increasing their metabolic rates and shifting substrate preferences from carbohydrates to carboxylic acids. While the utilization rates of some carbon sources remained stable, others showed significant changes—some increased (e.g., D-galactonic acid γ-lactone and itaconic acid), while others decreased (e.g., α-D-lactose and D-xylose). The most pronounced effects of warming were observed in June, coinciding with the onset of the growing season. These findings suggest that rising temperatures may substantially alter bacterial metabolic potential, contributing to a long-term positive feedback loop between lake nutrient cycling and climate change. Full article

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, plays a crucial role in acetaminophen (APAP)-induced hepatotoxicity. While 4-octyl itaconate (4-OI) demonstrates protective effects against APAP toxicity, its molecular mechanisms remain to be fully elucidated. Through an innovative integration of untargeted metabolomics and pathway analysis, we unveil a novel dual mechanism by which 4-OI prevents APAP-induced ferroptosis. We discovered that 4-OI stabilizes SLC7A11 through OTUB1-mediated deubiquitination, thereby restoring cystine import and glutathione (GSH) synthesis. In addition, 4-OI activates the Nrf2 pathway, orchestrating a comprehensive antioxidant response by upregulating the key proteins involved in both glutathione metabolism and iron homeostasis, including GPX4, FTH1, FTL1, and FPN1. This coordinated action effectively prevents the accumulation of toxic iron and lipid peroxides. Our findings not only elucidate the protective mechanisms of 4-OI but also establish it as a promising therapeutic candidate for ferroptosis-related diseases through its unique ability to simultaneously modulate the SLC7A11-GPX4 antioxidant axis and iron homeostasis. Full article

The necroptosis of granulosa cells has been proven to be one of the important triggers of follicular atresia, which is an important cause of reduced reproductive capacity in cows. The rapid growth of granulosa cells is accompanied by endoplasmic reticulum stress (ERS), leading to granulosa cell death. However, the link between ERS and necroptosis, as well as its mechanism in bovine granulosa cells is still unclear. Itaconic acid is an endogenous anti-inflammatory and antioxidant small-molecule compound that can alleviate ERS. Therefore, the aim of the current study is to evaluate the effect of ERS on necroptosis and investigate the ameliorative effect of itaconic acid against ERS-induced necroptosis in granulosa cells. Bovine granulosa cells were treated with tunicamycin (Tm) to induce ERS. After the addition of the necroptosis inhibitor Nec-1 and the detection of the necroptosis inducer acetylcholinesterase (AChE), flow cytometry, transmission electron microscopy, and mass spectrometry were used to analyze the expression of itaconic acid and IRG1 in the granulosa cells. In addition, the role of the PERK pathway downstream of ERS in ERS-induced necroptosis was also investigated. We report here that ERS can induce necroptosis in granulosa cells. Itaconic acid supplementation significantly attenuates the effect of ERS-induced damage. In summary, this research provides a scientific basis and a drug reference for treating follicular atresia and improving bovine reproductive capacity. Full article

This work demonstrates the fabrication of microstructures with formulations containing bio-based prepolymers derived from itaconic acid, commercial reactive diluents, photo initiators, and inhibitors, through two-photon polymerization. Lateral and vertical resolutions within the micron range can be achieved by the adjustment of laser scanning speed and pulse energy, and through the use of microscope objectives with high magnification and numerical aperture. The fabrication throughput can be slightly increased by simultaneously increasing the laser pulse energy and scanning speed, with special care to keep the resolution of the features that can be written via two-photon polymerization. Feasibility for the fabrication of 3D microstructures is demonstrated, through the fabrication of benchmark structures like woodpiles and pyramidal structures. Thus, this work proves that resins based on biobased formulations, originally designed for UV-curing 3D printing, can be adapted for two-photon polymerization, obtaining 3D microstructures with resolutions within the micron range. Full article

Leishmaniasis, caused by the Leishmania parasite, is a neglected public health issue. Leishmania mainly infects macrophages, where metabolic reprogramming shapes their plasticity (M1/M2), affecting the host’s resistance or susceptibility to infection. The development of this infection is influenced by immune responses, with an excessive anti-inflammatory reaction linked to negative outcomes through the modulation of various mediators. Itaconate, produced by the Acod1 gene, is recognized for its anti-inflammatory effects, but its function in leishmaniasis is not well understood. This study aimed to investigate the potential role of itaconate in leishmaniasis. Using transcriptomic data from L. major-infected BMDMs, we assessed the expression dynamics of Il1b and Acod1 and performed pathway enrichment analysis to determine the profile of genes co-expressed with Acod1. Early Acod1 upregulation followed by later Il1b downregulation was noted, indicating a shift towards an anti-inflammatory response. Among the genes co-expressed with Acod1, Ldlr, Hadh, and Src are closely associated with lipid metabolism and the polarization of macrophages towards the M2 phenotype, thereby creating a favorable environment for the survival of Leishmania. Overall, these findings suggest that Acod1 and its co-expressed genes may affect the outcome of Leishmania infection by modulating host metabolism. Accordingly, targeting itaconate-associated pathways could provide a novel therapeutic strategy for leishmaniasis. Full article