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1.
J Adv Res ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39357647

RESUMO

INTRODUCTION: Myocardial ischemia-reperfusion injury (MIRI) remains a prevalent clinical challenge globally, lacking an ideal therapeutic strategy. Macrophages play a pivotal role in MIRI pathophysiology, exhibiting dynamic inflammatory and resolutive functions. Macrophage polarization and metabolism are intricately linked to MIRI, presenting potential therapeutic targets. Pubescenoside C (PBC) from Ilex pubescens showed significantly anti-inflammatory effects, however, the effect of PBC on MIRI is unknown. OBJECTIVES: This study aimed to assess the cardioprotective effects of PBC against MIRI and elucidate the underlying mechanisms. METHODS: Sprague-Dawley rats, H9c2 and RAW264.7 macrophages were used to establish the in vitro and in vivo models of MIRI. TTC/Evans blue staining, immunohistochemical staining, metabonomics analysis, chemical probe, surface plasmon resonance (SPR), co-immunoprecipitation (CO-IP) assays were used for pharmacodynamic and mechanism study. RESULTS: PBC administration effectively reduced myocardial infarct size, decreased ST-segment elevation, and lowered CK-MB levels, concurrently promoting macrophage M2 polarization in MIRI. Furthermore, PBC-treated macrophages and their conditioned culture medium attenuated the apoptosis of H9c2 cells induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Metabonomics analysis revealed that PBC increased the production of itaconic acid (ITA) and malic acid (MA) in macrophages, which conferred protection against OGD/R injury in H9c2 cells. Mechanistic investigations indicated that ITA exerted its effects by covalently modifying pyruvate kinase M2 (PKM2) at Cys474, Cys424, and Lys151, thereby facilitating PKM2's mitochondrial translocation and enhancing the PKM2/Bcl2 interaction, subsequently leading to decreased degradation of Bcl2. SPR assays further revealed that PBC bound to HSP90, facilitating the interaction between HSP90 and GSK3ß and resulting in the inactivation of GSK3ß activity and upregulation of key metabolic enzymes for ITA and MA production (Acod1 and Mdh2). CONCLUSION: PBC alleviates MIRI-induced cardiomyocyte apoptosis by modulating the HSP90/ITA/PKM2 axis. Furthermore, pharmacological upregulation of ITA emerges as a promising therapeutic approach for MIRI, hinting at PBC's potential as a candidate drug for MIRI therapy.

2.
Polymers (Basel) ; 16(19)2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39408489

RESUMO

Environment-friendly polymer blends of poly(lactic acid) (PLA) and itaconic acid (IA), poly(itaconic acid) (PIA), poly(itaconic acid)-co-poly(methyl itaconate) (Cop-IA), and net-poly(itaconic acid)-ν-triethylene glycol dimethacrylate (Net-IA) were performed via melt blending. The compositions studied were 0.1, 1, 3, and 10 wt% of the diverse chemical architectures. The research aims to study and understand the effect of IA and its different architectures on the mechanical, rheological, and thermal properties of PLA. The PLA/IA, PLA/PIA, PLA/Cop-IA, and PLA/Net-IA blends were characterized by dynamic mechanical thermal analysis, rotational rheometer (RR), thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. The complex viscosity, storage module, and loss module for the RR properties were observed in the following order: PLA/Cop-IA, PLA/Net-IA, and PLA/PIA > PLA > PLA/IA. Thermal stability improved with increasing concentrations of Cop-IA and Net-IA. In the same way, the mechanical properties were enhanced. In addition, the micrographs illustrated the formation of fibrillar structures for all blends. The crystallinity degree displayed higher values for the blends that contain Net-IA > Cop-IA than IA > PIA. Therefore, IA and its architectures can influence these studied properties, which have potential applications in disposable food packing.

3.
Gels ; 10(9)2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39330204

RESUMO

In this study, poly(HEMA-PEGxMEM-IA) hydrogels were prepared by radical copolymerization of poly(ethylene glycol) methyl ether methacrylate (PEGxMEM), 2-hydroxyethyl methacrylate (HEMA), and itaconic acid (IA). The reaction was carried out in ethanolic solution using N,N'-methylenebisacrylamide (MBA) as a crosslinking agent and 1-hydroxycyclohexyl phenyl ketone (HCPK) as a photo-initiator. The poly(HEMA-PEGxMEM-IA) hydrogels (HGx) were evaluated as a delivery system for ursolic acid (UA), a phytochemical extracted from the plant Clinopodium revolutum, "flor de arena". The hydrogels were characterized by Fourier-transform infrared spectroscopy (FTIR-ATR), Raman spectroscopy, X-Ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The swelling behavior was studied in buffer solutions from pH 2 to 10, specifically at pH 2.2 (gastric environment) and 7.4 (intestinal environment). It was found that the hydrogels studied showed sensitivity to pH. At pH 2.2, the degree of swelling for HG5 and HG9 hydrogels was 0.45 and 0.93 (g water/g hydrogel), respectively. At pH 7.4, the degree of swelling for HG5 and HG9 hydrogels was 1.97 and 2.64 (g water/g hydrogel), respectively. The SEM images show the variation in pore size as a function of pH, and the UA crystals in the pores of the hydrogels can also be observed. The in vitro UA release data best fit the Korsmeyer-Peppas kinetic model and the diffusion exponent indicates that the release mechanism is governed by Fickian diffusion.

4.
Int J Mol Sci ; 25(18)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39337313

RESUMO

Itaconic acid (IA) is recognized for its potential application in treating intestinal diseases owing to the anti-inflammatory and antioxidant properties. Perfluorooctanoic acid (PFOA) can accumulate in animals and result in oxidative and inflammatory damages to multi-tissue and organ, particularly in the intestinal tract. This study aimed to explore whether IA could mitigate intestinal damage induced by PFOA exposure in laying hens and elucidate its potential underlying mechanisms. The results showed that IA improved the antioxidant capacity of laying hens and alleviated the oxidative damage induced by PFOA, as evidenced by the elevated activities of T-SOD, GSH-Px, and CAT, and the decreased MDA content in both the jejunum and serum. Furthermore, IA improved the intestinal morphological and structural integrity, notably attenuating PFOA-induced villus shedding, length reduction, and microvillus thinning. IA also upregulated the mRNA expression of ZO-1, Occludin, Claudin-1, and Mucin-2 in the jejunum, thereby restoring intestinal barrier function. Compared with the PF group, IA supplementation downregulated the gene expression of Keap1 and upregulated the HO-1, NQO1, SOD1, and GPX1 expression in the jejunum. Meanwhile, the PF + IA group exhibited lower expressions of inflammation-related genes (NF-κB, IL-1ß, IFN-γ, TNF-α, and IL-6) compared to the PF group. Moreover, IA reversed the PFOA-induced imbalance in gut microbiota by reducing the harmful bacteria such as Escherichia-Shigella, Clostridium innocuum, and Ruminococcus torques, while increasing the abundance of beneficial bacteria like Lactobacillus. Correlation analysis further revealed a significant association between gut microbes, inflammatory factors, and the Keap1/Nrf2/HO-1 pathway expression. In conclusion, dietary IA supplementation could alleviate the oxidative and inflammatory damage caused by PFOA exposure in the intestinal tract by reshaping the intestinal microbiota, modulating the Keap1/Nrf2/HO-1 pathway and reducing oxidative stress and inflammatory response, thereby promoting intestinal homeostasis.


Assuntos
Caprilatos , Fluorocarbonos , Microbioma Gastrointestinal , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Caprilatos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Galinhas , Heme Oxigenase-1/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/microbiologia , Feminino , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/patologia
5.
J Appl Biomater Funct Mater ; 22: 22808000241281273, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39295153

RESUMO

Vanillin loaded-physically crosslinked hydrogel membranes made of PVA/chitosan/itaconic acid (PVA-CS-IA) were prepared using freezing-thawing (F-T) cycle method. To ensure the entanglement of PVA-CS-IA chains, three F-T cycles were repeated. The polymeric chains entanglements were confirmed and characterized by different instrumental characterizations. Physicochemical properties for example, swelling ratio, mechanical characteristics, gel fraction percentage (GF%), hydrolytic degradation, and thermal stability of PVA-CS-IA membrane were discussed in detail. The findings showed that the swelling ratio, mechanical characteristics, and hydrolytic degradation of the crosslinked membranes enhanced with increasing CS-IA contents in membranes composition; however, GF% gradually declined with CS-IA content. Additionally, cell viability test using HFB-4 cell line and antimicrobial activity against Staphylococcus aureus and Escherichia coli were evaluated using MTT assay and the bacterium growth inhibition percentage method; respectively. Notably, with varying incubation durations and membrane concentrations, all examined constructed hydrogels showed significant cell survival percentages. The findings supported the notion that produced hydrogel membranes might be used in a professional setting as antibacterial dressings or biomaterials for quick wound healing rate.


Assuntos
Antibacterianos , Benzaldeídos , Quitosana , Escherichia coli , Álcool de Polivinil , Staphylococcus aureus , Cicatrização , Quitosana/química , Quitosana/farmacologia , Álcool de Polivinil/química , Cicatrização/efeitos dos fármacos , Humanos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Benzaldeídos/química , Benzaldeídos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Linhagem Celular , Membranas Artificiais , Hidrogéis/química , Hidrogéis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Succinatos
6.
ChemSusChem ; : e202401499, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39207277

RESUMO

Paper used for packaging applications is often coated with thin polymer coatings to improve the properties, like printability and barrier properties, respectively. Today, these coatings are still often based on petroleum-based polymers. In this study, the fabrication of biobased thin film coatings is described. Poly(itaconic acid ester)s, which are prepared by emulsion poly-meri-zation, are used as water-based coatings for paper. The thermal properties of the polymers are tuned by the side chain of the monomers (diethyl itaconate vs. dibutyl itaconate). Different formulations based on the polymer emulsion and additives, like rheology modifiers, are prepared and their film formation is studied. The usage of Rheobyk-7420 CA as rheology modifier results in excellent film formation. These polymer coatings feature an additional function - they are capable of self-healing. The healing ability is studied in scratch healing tests, in which almost complete recovery can be observed after healing at 100 °C. Moreover, the restoration of optical properties / aesthetics is studied. In gloss measurements before and after damage as well as after a healing time the complete recovery of the gloss can be observed. Furthermore, the barrier properties against fat are studied.

7.
J Chromatogr A ; 1734: 465251, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39191184

RESUMO

In this study, we propose a model for the simulation of the pH-dependent separation of dicarboxylic acids from aqueous solutions using strongly hydrophobic adsorbents. Building upon results of our previous study, where we experimentally investigated the pH-dependent adsorption behavior of the individual acid species of itaconic acid (IA) on a strongly hydrophobic adsorbent using in-line Raman spectroscopy, we utilize a transport-dispersive model as the basis for our simulation model. Instead of considering IA as a single component in our model, we simulated each acid species of IA individually. For this purpose, we expanded the transport-dispersive model with reaction terms in all aqueous phases. The reaction terms include all dissociation reactions of all involved components for each time step and spatial discretization. This model enables the time and spatial dependent simulation of the pH value in the chromatographic column and thus the time and spatial dependent knowledge of each acid species concentration. The consideration of activity coefficients due to high local ionic strength is achieved using the Truesdell-Jones (TdJ) model. The simulation model is successfully validated using experimental data from our previous study and used in a simulation study that demonstrates the potential of the model approach for analyzing associated separation tasks.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Succinatos , Succinatos/química , Concentração de Íons de Hidrogênio , Adsorção , Modelos Químicos , Análise Espectral Raman , Concentração Osmolar
8.
Cell Commun Signal ; 22(1): 413, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192276

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant tumor of epithelial origin in head and neck with high incidence rate in South China, Southeast Asia and North Africa. The intervention of tumor-associated macrophages (Mφs) (TAMs)-mediated immunosuppression is a potential therapeutic strategy against tumor metastasis, but the exact mechanisms of TAM-mediated immunosuppression in nasopharyngeal carcinoma are unclear. Furthermore, how TAM affects the occurrence and development of nasopharyngeal carcinoma through metabolism is rarely involved. In this work, we revealed that NPC cells promoted M2-type Mφ polarization and elevated itaconic acid (ITA) release. Also, TAMs facilitated NPC cell proliferation, migration, and invasion through immune response gene 1 (IRG1)-catalyzed ITA production. Then, IRG1-mediated ITA production in TAMs repressed the killing of CD8+ T cells, induced M2-type polarization of TAMs, and reduced the phagocytosis of TAMs. Moreover, we demonstrated ITA played a tumor immunosuppressive role by binding and dampening ten-eleven translocation-2 (TET2) expression. Finally, we proved that ITA promotes NPC growth by facilitating immune escape in CD34+ hematopoietic stem cell humanized mice. In Conclusion, TAM-derived ITA facilitated NPC progression by enhancing immune escape through targeting TET2, highlighting that interfering with the metabolic pathway of ITA may be a potential strategy for NPC treatment.


Assuntos
Proteínas de Ligação a DNA , Dioxigenases , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteínas Proto-Oncogênicas , Succinatos , Evasão Tumoral , Macrófagos Associados a Tumor , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Humanos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Animais , Camundongos , Succinatos/farmacologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/metabolismo , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Progressão da Doença , Proliferação de Células , Movimento Celular/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Carboxiliases
9.
Sheng Wu Gong Cheng Xue Bao ; 40(8): 2666-2677, 2024 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-39174475

RESUMO

Itaconic acid (IA) is one of the twelve high value-added platform compounds applied in various fields including coatings, adhesives, plastics, resins, and biofuels. In this study, we established a one-pot catalytic synthesis system for IA from citric acid based on the engineered salt-tolerant bacterial strain Halomonas bluephagenesis TDZI-08 after investigating factors that hindered the process and optimizing the carbon source, nitrogen source, inducer addition time, and surfactant dosage. The open, non-sterile, one-pot synthesis with TDZI-08 in a 5 L fermenter achieved the highest IA titer of 40.50 g/L, with a catalytic yield of 0.68 g IA/g citric acid during the catalytic stage and a total yield of 0.42 g IA/g (citric acid+gluconic acid). The one-pot synthesis system established in this study is simple and does not need sterilization or aseptic operations. The findings indicate the potential of H. bluephagenesis for industrial production of IA.


Assuntos
Halomonas , Succinatos , Halomonas/metabolismo , Halomonas/genética , Succinatos/metabolismo , Engenharia Metabólica , Microbiologia Industrial , Ácido Cítrico/metabolismo , Fermentação
10.
Int J Toxicol ; 43(4_suppl): 5-41, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39045851

RESUMO

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 30 vinylpyrrolidone polymers as used in cosmetic products; most of these ingredients have the reported cosmetic function of film former in common. The Panel reviewed data relevant to the safety of these ingredients, and determined that 27 vinylpyrrolidone polymers are safe in cosmetics in the present practices of use and concentration described in the safety assessment. The Panel also concluded that the available data are insufficient to make a determination that 3 vinylpyrrolidone polymers (all urethanes) are safe under the intended conditions of use in cosmetic formulations.


Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos , Polímeros , Pirrolidinonas , Cosméticos/toxicidade , Cosméticos/química , Humanos , Animais , Polímeros/toxicidade , Polímeros/química , Pirrolidinonas/toxicidade , Pirrolidinonas/química , Pirrolidinonas/farmacocinética , Testes de Toxicidade , Medição de Risco
11.
FEMS Yeast Res ; 242024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-39038994

RESUMO

Ustilago maydis and Ustilago cynodontis are natural producers of a broad range of valuable molecules including itaconate, malate, glycolipids, and triacylglycerols. Both Ustilago species are insensitive toward medium impurities, and have previously been engineered for efficient itaconate production and stabilized yeast-like growth. Due to these features, these strains were already successfully used for the production of itaconate from different alternative feedstocks such as molasses, thick juice, and crude glycerol. Here, we analyzed the amylolytic capabilities of Ustilago species for metabolization of starch, a highly abundant and low-cost polymeric carbohydrate widely utilized as a substrate in several biotechnological processes. Ustilago cynodontis was found to utilize gelatinized potato starch for both growth and itaconate production, confirming the presence of extracellular amylolytic enzymes in Ustilago species. Starch was rapidly degraded by U. cynodontis, even though no α-amylase was detected. Further experiments indicate that starch hydrolysis is caused by the synergistic action of glucoamylase and α-glucosidase enzymes. The enzymes showed a maximum activity of around 0.5 U ml-1 at the fifth day after inoculation, and also released glucose from additional substrates, highlighting potential broader applications. In contrast to U. cynodontis, U. maydis showed no growth on starch accompanied with no detectable amylolytic activity.


Assuntos
Amido , Succinatos , Ustilago , Ustilago/metabolismo , Ustilago/genética , Ustilago/enzimologia , Ustilago/crescimento & desenvolvimento , Amido/metabolismo , Succinatos/metabolismo , Glucana 1,4-alfa-Glucosidase/metabolismo , Hidrólise
12.
ACS Appl Mater Interfaces ; 16(31): 41461-41474, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39049199

RESUMO

The demand for underwater pressure sensitive adhesives (PSAs) is rapidly increasing in fields such as underwater engineering and biomedicine. However, the achievement of underwater adhesion of PSAs remains a challenge because of the hydration layer that hinders the interaction between the adhesive and the substrate. Herein, a new type of underwater PSA was synthesized by the copolymerization of hydrophobic unsaturated poly(1,2-butylene oxide) (UPBO) and hydrophilic itaconic acid monomers using solvent-free ultraviolet curing. The PSA has demonstrated substrate-independent underwater adhesion strengths ranging from 108 to 141 kPa on both hydrophilic (glass, wood, steel) and hydrophobic (PET, PMMA, PTFE) substrates. The underwater adhesion performance of PSA remains stable during 30 adhesion-detachment cycles and incubation in water for 20 days. Notably, PSA shows cytocompatibility, antimicrobial, and degradable properties and can be used for rapid hemostasis of skin wounds. Experimental characterizations confirm that the process of underwater adhesion is achieved by hydrophobic alkyl side chains of the PBO chain segments, which repel water at the adhesive-substrate interface. This study should provide both practical and facile design strategies for multifunctional underwater PSAs that can be used in a variety of applications.

14.
Biotechnol Biofuels Bioprod ; 17(1): 103, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020434

RESUMO

BACKGROUND: Itaconic acid is a promising bio-based building block for the synthesis of polymers, plastics, fibers and other materials. In recent years, Ustilago cynodontis has emerged as an additional itaconate producing non-conventional yeast, mainly due to its high acid tolerance, which significantly reduces saline waste coproduction during fermentation and downstream processing. As a result, this could likely improve the economic viability of the itaconic acid production process with Ustilaginaceae. RESULTS: In this study, we characterized a previously engineered itaconate hyper-producing Ustilago cynodontis strain in controlled fed-batch fermentations to determine the minimal and optimal pH for itaconate production. Under optimal fermentation conditions, the hyper-producing strain can achieve the theoretical maximal itaconate yield during the production phase in a fermentation at pH 3.6, but at the expense of considerable base addition. Base consumption is strongly reduced at the pH of 2.8, but at cost of production yield, titer, and rate. A techno-economic analysis based on the entire process demonstrated that savings due to an additional decrease in pH control reagents and saline waste costs cannot compensate the yield loss observed at the highly acidic pH value 2.8. CONCLUSIONS: Overall, this work provides novel data regarding the balancing of yield, titer, and rate in the context of pH, thereby contributing to a better understanding of the itaconic acid production process with Ustilago cynodontis, especially from an economic perspective.

15.
Polymers (Basel) ; 16(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38931999

RESUMO

Thermosetting polymers and composites are a class of high-performance materials with significant industrial applications. However, the widespread use of thermosets and their composites generates large quantities of waste and leads to serious economic and environmental problems, there is a critical need in the elaboration of sustainable composite materials. Here, we propose a method to prepare sustainable carbon fiber reinforced composites with different degrees of greenness by blending environmentally friendly EIA with DGEBA in different ratios, and the properties compared with a well-known commercial petroleum-based epoxy resin. The prepared carbon fiber reinforced polymer (CFRP) composites with different degrees of greenness had excellent dimensional stability under extreme hygrothermal aging. After aging, the green CFRP composite T700/EIA-30 has higher strength and performance retention than that of petroleum-based CFRP composites. The higher hygrothermal stability and durability of EIA-based epoxy resins as compared with BPA-based epoxy resins demonstrated significant evidence to design and develop a novel bio-based epoxy resin with high performance to substitute the petroleum-based epoxy resin.

16.
Chemistry ; 30(49): e202401754, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-38923037

RESUMO

Leveraging electrochemistry, a new synthesis of non-natural derivatives of itaconic acid is proposed by utilizing carbon dioxide (CO2) as a valuable C1 synthon. An electrochemical cross-electrophile coupling between allenoates and CO2 was targeted, allowing for the synthesis of both mono- and di-carboxylation products in a catalyst- and additive-free environment (yields up to 87 %, 30 examples). Elaboration of the model mono-carboxylation product, and detailed cyclovoltammetric, as well as mechanistic analyses complete the present investigation.

17.
Phytomedicine ; 130: 155761, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38797031

RESUMO

BACKGROUND: Quercetin has received extensive attention for its therapeutic potential treating respiratory syncytial virus (RSV) infection diseases. Recent studies have highlighted quercetin's ability of suppressing alveolar macrophages (AMs)-derived lung inflammation. However, the anti-inflammatory mechanism of quercetin against RSV infection still remains elusive. PURPOSE: This study aims to elucidate the mechanism about quercetin anti-inflammatory effect on RSV infection. METHODS: BALB/c mice were intranasally infected with RSV and received quercetin (30, 60, 120 mg/kg/d) orally for 3 days. Additionally, an in vitro infection model utilizing mouse alveolar macrophages (MH-S cells) was employed to validate the proposed mechanism. RESULTS: Quercetin exhibited a downregulatory effect on glycolysis and tricarboxylic acid (TCA) cycle metabolism in RSV-infected AMs. However, it increased itaconic acid production, a metabolite derived from citrate through activating immune responsive gene 1 (IRG1), and further inhibiting succinate dehydrogenase (SDH) activity. While the suppression of SDH activity orchestrated a cascading downregulation of Hif-1α/NLRP3 signaling, ultimately causing AMs polarization from M1 to M2 phenotypes. CONCLUSION: Our study demonstrated quercetin stimulated IRG1-mediated itaconic acid anabolism and further inhibited SDH/Hif-1α/NLRP3 signaling pathway, which led to M1 to M2 polarization of AMs so as to ameliorate RSV-induced lung inflammation.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Macrófagos Alveolares , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR , Quercetina , Infecções por Vírus Respiratório Sincicial , Succinatos , Animais , Succinatos/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Quercetina/farmacologia , Camundongos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Succinato Desidrogenase/metabolismo , Glicólise/efeitos dos fármacos , Feminino , Transdução de Sinais/efeitos dos fármacos , Ciclo do Ácido Cítrico/efeitos dos fármacos , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Hidroliases
18.
Biotechnol Lett ; 46(4): 593-600, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38809464

RESUMO

Itaconic acid is an excellent polymeric precursor with a wide range of industrial applications. The efficient production of itaconate from various renewable substrates was demonstrated by engineered Escherichia coli. However, limitation in the itaconic acid precursor supply was revealed by finding out the key intermediate of the tricarboxylic acid in the itaconic acid pathway. Efforts of enhancing the cis-aconitate flux and preserving the isocitrate pool to increase itaconic acid productivity are required. In this study, we introduce a synthetic protein scaffold system between CadA and AcnA to physically combine the two enzymes. Through the introduction of a synthetic protein scaffold, 2.1 g L-1 of itaconic acid was produced at pH 7 and 37 °C. By fermentation, 20.1 g L-1 for 48 h of itaconic acid was produced with a yield of 0.34 g g-1 glycerol. These results suggest that carbon flux was successfully increased itaconic acid productivity.


Assuntos
Escherichia coli , Engenharia Metabólica , Succinatos , Succinatos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Engenharia Metabólica/métodos , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Fermentação
19.
Biotechnol Biofuels Bioprod ; 17(1): 57, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685114

RESUMO

Lignocellulose was directly used in itaconic acid production by a model filamentous fungus Neurospora crassa. The promoters of two clock control genes and cellobiohydrolase 1 gene were selected for heterologous genes expression by evaluating different types of promoters. The effect of overexpression of different cellulase was compared, and it was found that expression of cellobiohydrolase 2 from Trichoderma reesei increased the filter paper activity by 2 times, the cellobiohydrolase activity by 4.5 times, and that the itaconic acid titer was also significantly improved. A bidirectional cis-aconitic acid accumulation strategy was established by constructing the reverse glyoxylate shunt and expressing the transporter MTTA, which increased itaconic acid production to 637.2 mg/L. The simultaneous optimization of cellulase and metabolic pathway was more conducive to the improvement of cellulase activity than that of cellulase alone, so as to further increase itaconic acid production. Finally, through the combination of fermentation by optimized strains and medium optimization, the titers of itaconic acid using Avicel and corn stover as substrate were 1165.1 mg/L and 871.3 mg/L, respectively. The results prove the potential of the consolidated bioprocessing that directly converts lignocellulose to itaconic acid by a model cellulase synthesizing strain.

20.
Int J Biol Macromol ; 268(Pt 2): 131604, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38641270

RESUMO

This study aims to develop pH-sensitive and controlled release of ciprofloxacin from ciprofloxacin-loaded grafted chitosan-coated zinc oxide nanoparticles (Cip@Gchit/Zn-NPs) for the treatment of bacterial infections in the human colon. For this aim, first, the chitosan-g-poly(itaconic acid) [Chit-g-poly (Itac)] was synthesized via grafting of itaconic acid onto chitosan in the presence of cerium ammonium nitrate (CAN) under an inert atmosphere using conventional methods, while zinc oxide nanoparticles (Zn-NPs) were prepared via sol-gel technique. Characterization of the synthesized Cip@Gchit/Zn-NPs was analyzed using XRD, FT-IR, SEM, TGA, and zeta potential analysis. The antibacterial efficacy of Cip@Gchit/Zn-NPs against three pathogenic bacteria, namely Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, was superior to that of tetracycline reference drugs, as evidenced by larger inhibition zones. Cytotoxicity assessment of Cip@Gchit/Zn-NPs on the human chondrocyte cell line C28/I2 via MTT assay revealed 100 % cell viability at a concentration of 500 µg/mL. The loading efficiency of ciprofloxacin into Gchit/Zn-NPs was evaluated at various ratios, demonstrating lower loading efficiency; however, sustained release of ciprofloxacin from Cip@Gchit/Zn-NPs was excellent, with 98.13 % release observed at pH 7.2 over 10 h. Kinetic analysis of ciprofloxacin release followed the first-order kinetic models.


Assuntos
Antibacterianos , Quitosana , Ciprofloxacina , Portadores de Fármacos , Succinatos , Quitosana/química , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Ciprofloxacina/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química , Succinatos/química , Humanos , Nanopartículas/química , Liberação Controlada de Fármacos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
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