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1.
Front Nutr ; 11: 1406817, 2024.
Article in English | MEDLINE | ID: mdl-38746936

ABSTRACT

Russula, a renowned edible fungus, has gained popularity as a functional food among diverse populations due to the abundant presence of amino acids, proteins, and polysaccharides. As the primary constituents of Russula, polysaccharides exhibit a wide range of biological properties, making them an exceptional choice for incorporation into food, medicines, and diverse biotechnological applications. This review provides a summary of the recent research on the extraction, purification, and biological applications of polysaccharides from various Russula spp. Currently, there are many advanced extraction technologies, such as hot water-based extraction, alkali-based extraction, ultrasonic-assisted extraction and microwave-assisted extraction. Hence, the latest progress of extraction technologies, as well as their advantages and limitations will be discusses and summarizes in this review. The separation and purification methods of polysaccharide from Russula were introduced, including ethanol precipitation, deproteinization and gel filtration chromatography. It also focuses on exploring the diverse bioactive capabilities of Russula, including anti-oxidant, anti-tumor, immunomodulatory, anti-inflammation, and anti-bacterial properties. Hence, this review aims to foster a comprehensive understanding of the polysaccharides from various Russula spp. and pave the way for their promising and potential future applications in the medical and functional fields.

3.
Food Chem ; 445: 138662, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38354641

ABSTRACT

Understanding the basic solubilization of fish myofibrillar proteins (MPs) in common monovalent chloride solutions is crucial for muscle food processing. In this study, the differential proteomic profiles of MPs during extraction and solubilization in NaCl and KCl solutions were investigated by using advanced four-dimensional data-independent acquisition (4D DIA) quantitative proteomics for the first time. Compared to routine biochemical analysis, this could provide insights into the solubilization of muscle proteins. We ensure the consistency of the effective ionic strength of NaCl and KCl buffers by adjusting the conductivity. The results showed that NaCl extractor mainly facilitated the solubilization of cytoskeletal proteins, biochemical enzymes, and stromal proteins compared to KCl, such as tubulin, myosin-9, collagen, plectin, protein phosphatase, and cathepsin D. However, no significant difference was observed in the extraction of major sarcomeric proteins, including myosin, actin, troponin C, myosin-binding protein C, M-Protein, α-actinin-3, and tropomyosin.


Subject(s)
Fish Proteins , Sodium Chloride , Animals , Sodium Chloride/pharmacology , Fish Proteins/metabolism , Proteomics , Myofibrils/metabolism , Myosins/metabolism , Actins/metabolism
4.
Food Chem ; 443: 138568, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38301564

ABSTRACT

Previous studies showed that transglutaminase (TGase) and microwaves acted synergistically to improve the functional properties of proteins. The mechanism behind this has yet to be elucidated. In this study, the phenomenon of microwaves enhancing TGase activity was experimentally validated. Molecular docking and molecular dynamics simulations revealed that moderate microwaves (105 and 108 V/m) increased the structural flexibility of TGase and promoted the orientation of the side chain carboxylate anion group on Asp255, driving the reaction forward. Also, TGase underwent partial transformation from α-helix to turns or coils at 105 and 108 V/m, exposing more residues in the active site and facilitating the binding of the substrate (CBZ-Gln-Gly) to TGase. However, 109 V/m microwaves completely destroyed the TGase structure, inactivating the enzyme. This study provides insights into the molecular mechanisms underlying the interactions between TGase and substrate subjected to microwaves, promoting the future applications of TGase and microwaves in food processing.


Subject(s)
Molecular Dynamics Simulation , Transglutaminases , Transglutaminases/metabolism , Molecular Docking Simulation , Microwaves , Proteins
5.
J Agric Food Chem ; 72(9): 4991-5002, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38346801

ABSTRACT

Brown discoloration was observed in the crust of commercial frozen steamed stuffed buns (FSSBs) during resteaming. Culture-dependent and culture-independent analyses demonstrated that Serratia marcescens, a prodigiosin-producing species, was more abundant in spoiled samples than in unspoiled samples. Inoculation of experimental FSSBs with S. marcescens isolated from spoiled FSSBs confirmed that this species causes brown discoloration of FSSBs during resteaming. S. marcescens formed prodigiosin only between 15 and 28 °C but brown discoloration appeared only upon resteaming after storage at 4 °C. High-performance liquid chromatography analyses revealed that prodigiosin was absent from yellow-brown FSSBs. The pigmentation observed during resteaming is thus likely attributable to the intermediate 2-methyl-3-amylpyrrole. These findings provide valuable insights into the microbial contamination of FSSBs and will facilitate the prevention of spoilage of FSSBs.


Subject(s)
Prodigiosin , Serratia marcescens , Pigmentation , Freezing
6.
J Agric Food Chem ; 72(2): 1376-1390, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38165648

ABSTRACT

The coverage of the protein database directly determines the results of shotgun proteomics. In this study, PacBio single-molecule real-time sequencing technology was performed on postmortem silver carp muscle transcripts. A total of 42.43 Gb clean data, 35,834 nonredundant transcripts, and 15,413 unigenes were obtained. In total, 99.32% of the unigenes were successfully annotated and assigned specific functions. PacBio long-read isoform sequencing (Iso-Seq) analysis can provide more accurate protein information with a higher proportion of complete coding sequences and longer lengths. Subsequently, 2671 proteins were identified in deep 4D proteomics informed by a full-length transcriptomics technique, which has been shown to improve the identification of low-abundance muscle proteins and potential protein isoforms. The feature of the sarcomeric protein profile and information on more than 30 major proteins in the white dorsal muscle of silver carp were reported here for the first time. Overall, this study provides valuable transcriptome data resources and the comprehensive muscle protein information detected to date for further study into the processing characteristic of early postmortem fish muscle, as well as a spectral library for data-independent acquisition and data processing. This batch of muscle-specific dependent acquisition data is available via PRIDE with identifier PXD043702.


Subject(s)
Carps , Transcriptome , Animals , Proteomics , Proteome/genetics , Carps/genetics , Protein Isoforms/genetics , Muscles
7.
Epigenomes ; 7(4)2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38131904

ABSTRACT

Hematopoietic stem cells (HSCs) are essential for maintaining overall health by continuously generating blood cells throughout an individual's lifespan. However, as individuals age, the hematopoietic system undergoes significant functional decline, rendering them more susceptible to age-related diseases. Growing research evidence has highlighted the critical role of epigenetic regulation in this age-associated decline. This review aims to provide an overview of the diverse epigenetic mechanisms involved in the regulation of normal HSCs during the aging process and their implications in aging-related diseases. Understanding the intricate interplay of epigenetic mechanisms that contribute to aging-related changes in the hematopoietic system holds great potential for the development of innovative strategies to delay the aging process. In fact, interventions targeting epigenetic modifications have shown promising outcomes in alleviating aging-related phenotypes and extending lifespan in various animal models. Small molecule-based therapies and reprogramming strategies enabling epigenetic rejuvenation have emerged as effective approaches for ameliorating or even reversing aging-related conditions. By acquiring a deeper understanding of these epigenetic mechanisms, it is anticipated that interventions can be devised to prevent or mitigate the rates of hematologic aging and associated diseases later in life. Ultimately, these advancements have the potential to improve overall health and enhance the quality of life in aging individuals.

8.
Article in English | MEDLINE | ID: mdl-37906941

ABSTRACT

Gellan, an anionic heteropolysaccharide synthesized by Sphingomonas elodea, is an excellent gelling agent. However, its poor mechanical strength and high gelling temperature limit its application. Recent studies have reported that combining gellan with other polysaccharides achieves desirable properties for food- and biomaterial-related applications. This review summarizes the fabrication methods, functional properties, and potential applications of gellan-polysaccharide systems. Starch, pectin, xanthan gum, and konjac glucomannan are the most widely used polysaccharides in these composite systems. Heating-cooling and ionic-induced cross-linking approaches have been used in the fabrication of these systems. Composite gels fabricated using gellan and various polysaccharides exhibit different functional properties, possibly because of their distinct molecular interactions. In terms of applications, mixed gellan-polysaccharide systems have been extensively used in texture modification, edible coatings and films, bioactive component delivery, and tissue-engineering applications. Further scientific studies, including structural determinations of mixed systems, optimization of processing methods, and expansion of applications in food-related fields, are needed. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 15 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

9.
Int J Mol Sci ; 24(17)2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37686227

ABSTRACT

Xylo-oligosaccharides (XOS) enriched with high fractions of X2-X3 are regarded as an effective prebiotic for regulating the intestinal microflora. In this study, the original XOS solution was obtained from bamboo shoots through hydrothermal pretreatment under optimized conditions. Subsequently, enzymatic hydrolysis with endo-xylanase was performed on the original XOS solution to enhance the abundance of the X2-X3 fractions. The results demonstrated that hydrothermal pretreatment yielded 21.24% of XOS in the hydrolysate solution, and subsequent enzymatic hydrolysis significantly increased the proportion of the X2-X3 fractions from 38.87% to 68.21%. Moreover, the XOS solutions with higher amounts of X2-X3 fractions exhibited superior performance in promoting the growth of probiotics such as Bifidobacterium adolescentis and Lactobacillus acidophilus in vitro, leading to increased production of short-chain fatty acids. In the in vivo colitis mouse model, XOS solutions with higher contents of X2-X3 fractions demonstrated enhanced efficacy against intestinal inflammation. Compared with the colitis mice (model group), the XOS solution with higher X2-X3 fractions (S1 group) could significantly increase the number of Streptomyces in the intestinal microflora, while the original XOS solution (S2 group) could significantly increase the number of Bacteroides in the intestinal microflora of colitis mice. In addition, the abundances of Alcaligenes and Pasteurella in the intestinal microflora of the S1 and S2 groups were much lower than in the model group. This effect was attributed to the ability of these XOS solutions to enhance species diversity, reversing the imbalance and disorder within the intestinal microflora. Overall, this work highlights the outstanding potential of XOS enriched with high contents of X2-X3 fractions as a regulator of the intestinal microbiota and as an anti-colitis agent.


Subject(s)
Colitis , Endometriosis , Probiotics , Animals , Mice , Female , Humans , Prebiotics , Hydrolysis , Bacteroides , Colitis/drug therapy , Oligosaccharides/pharmacology , Vegetables
10.
Curr Res Food Sci ; 7: 100581, 2023.
Article in English | MEDLINE | ID: mdl-37691697

ABSTRACT

As a novel protein resource, the low digestibility of Spirulina platensis protein (SPP) limits its large-scale application. From the perspective of food processing methods, different heating treatments were explored to improve the structure and digestibility of SPP. In this study, SPP was heated by water bath and microwave at the same heating rate and heating temperature. Microwave accelerated protein denaturation and structure unfolded as the heating intensity increases, causing more exposed hydrophobic residues and enhancing surface hydrophobicity. The data of free sulfhydryl group, particle size, and gel electrophoresis, showed that microwave treatment promoted the formation of protein aggregates. The structural changes can potentially improve the accessibility of digestive enzymes, promote the in vitro digestibility rate, and further accelerate the production of small molecular peptides and the release of free amino acids. This study provided an innovative approach to improve the digestibility and therefore the utilization efficiency of SPP.

11.
J Agric Food Chem ; 71(37): 13920-13933, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37688549

ABSTRACT

In this study, changes in the physical, structural, and assembly characteristics of silver carp myofibrillar proteins (MPs) at different ionic strength (I) values were investigated. Moreover, the differential proteomic profile of soluble MPs was analyzed using 4D proteomics based on timsTOF Pro mass spectrometry. Solubility of MPs significantly increased at high I (>0.3), and the increase in I enhanced the apparent viscosity, fluorescence intensity, surface hydrophobicity, and α-helix content of MPs solution. Particle size and sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns also supported the solubility profiles. Transmission electron microscopy and atomic force microscopy observations revealed the morphological assembly and disassembly of MPs under different I conditions. Finally, proteomic analysis revealed the evolution law of salt-induced solubilization of MPs and the critical molecular characteristics in different I environments. The number of differentially abundant proteins (DAPs) decreased with the increase of I, and most DAPs related to the muscle filament sliding, contraction and assembly, actinin binding, and actin filament binding. The soluble abundance of myosin and some structural proteins was dependent on I, and structural proteins in the Z-disk and M-band might contribute to the solubilization of myosin. Our findings provide insightful information about the impact of common I on the solubility pattern of MPs from freshwater fish.


Subject(s)
Carps , Proteomics , Animals , Electrophoresis, Polyacrylamide Gel , Fresh Water , Mass Spectrometry
12.
FASEB J ; 37(10): e23143, 2023 10.
Article in English | MEDLINE | ID: mdl-37698353

ABSTRACT

Cuproptosis, a new type of copper-induced cell death, is involved in the antitumor activity and resistance of multiple chemotherapeutic drugs. Our previous study revealed that adrenomedullin (ADM) was engaged in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). However, it has yet to be investigated whether and how ADM regulates sunitinib resistance by cuproptosis. This study found that the ADM expression was elevated in sunitinib-resistant ccRCC tissues and cells. Furthermore, the upregulation of ADM significantly enhanced the chemoresistance of sunitinib compared with their respective control. Moreover, cuproptosis was involved in ADM-regulated sunitinib resistance by inhibiting mammalian ferredoxin 1 (FDX1) expression. Mechanically, the upregulated ADM activates the p38/MAPK signaling pathway to promote Forkhead box O3 (FOXO3) phosphorylation and its entry into the nucleus. Consequently, the increased FOXO3 in the nucleus inhibited FDX1 transcription and cell cuproptosis, promoting chemoresistance. Collectively, cuproptosis has a critical effector role in ccRCC progress and chemoresistance and thus is a relevant target to eradicate the cell population of sunitinib resistance.


Subject(s)
Apoptosis , Carcinoma, Renal Cell , Carcinoma , Kidney Neoplasms , Animals , Adrenomedullin/genetics , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Sunitinib/pharmacology , Copper
13.
Int J Biol Macromol ; 251: 126296, 2023 Aug 11.
Article in English | MEDLINE | ID: mdl-37573908

ABSTRACT

This study targeted the sustainable utilization of chitin and chitosan from crayfish shell waste, and further depolymerization of the recovered products in one step through synergy between microwaves and graphene oxide, aiming for the monosaccharides, 5-hydroxymethylfurfural and other high-value products. The results indicated that graphene oxide was more effective than graphene in enhancing the microwave absorption properties of the system, which is contrary to the parameters of their dielectric properties. The heating rate was increased by 0.37 K/s and 0.26 K/s when graphene oxide was introduced into the chitin and chitosan depolymerization systems, respectively, at a microwave power of 5 W/g. The mechanism underlying the impact of graphene oxide on chitin and chitosan under a microwave field was proposed by analyzing the variations in the depolymerization products of chitin and chitosan systems under different reaction conditions, including holding time, catalyst content, solvent content, and reaction temperature. Furthermore, the recovered graphene oxide exhibited delamination upon redispersion in water, which was not observed in the initial samples. The infrared spectra and scanning electron microscopy results suggest that the catalytic reaction is associated with oxygen-containing functional groups. This study demonstrated the synergistic effect of microwaves and graphene oxide on the depolymerization of chitin and chitosan, and the ability to achieve rapid one-step depolymerization in an acid/alkali-free solvent, which provides a green and promising development for the degradation of carbohydrate macromolecules in crustacean solid waste.

14.
Food Chem ; 427: 136642, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37364317

ABSTRACT

Low-molecular-weight-galactomannan (LMW-GM) is an edible polysaccharide with various biological activities. However, it is used in the field of neuroprotection. In this study, two types of LMW-GMs from Sesbania cannabina were obtained by gluconic acid extraction (GA-LMW-GM) and enzymatic hydrolysis (GMOS). The structure of GA-LMW-GM and GMOS were identified using different nuclear magnetic resonance (NMR) techniques. The antioxidant and neuroprotective activities of GA-LMW-GM and GMOS were evaluated in vitro/vivo. The results showed that both GA-LMW-GM and GMOS possess good free radicals scavenging ability in vitro with IC50 values of 1.9 mg/mL and 4.9 mg/mL for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals 2.8 mg/mL and 4.4 mg/mL for O2•- radicals, respectively. However, GA-LMW-GM was more effective at scavenging reactive oxygen species (ROS) in vivo and protecting the fundamental growth (with a recovery capability of 62.5%) and locomotor functions (with recovery capability of 193.7%) of zebrafish with neurological damage induced by Bisphenol AF.


Subject(s)
Sesbania , Animals , Antioxidants/pharmacology , Molecular Weight , Neuroprotection , Sesbania/chemistry , Zebrafish
15.
Int J Biol Macromol ; 231: 123356, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36682655

ABSTRACT

The lack of a sufficient amount of functional groups in the lignin structure limits its bioapplication. In this work, high-pressure homogenization was performed on original kraft lignin (L-ORI) to prepare lignin nanoparticles (L-NANO), which aimed to improve its functional group contents for further vascular and neurological applications. The results showed that the prepared L-NANO possessed spherical structures with diameters of 40.3-160.4 nm and increased amount of hydroxyl groups. Compared to L-ORI, L-NANO possessed better in vivo and in vitro antioxidant capacity, which could endow it with enhanced protective effects for the vascular and neural development of bisphenol AF (BPAF)-induced zebrafish. In addition, L-NANO reduced the neurotoxicity and cardiovascular toxicity of BPAF in zebrafish by upregulating the expression levels of oxidative stress-related genes (Cu/Zn-Sod and cat), which could further significantly upregulate the expression levels of neurogenesis genes (elavl3, gap43, mbp, and syn2a) and protect the contraction of the cardinal vein (CCV) and early central nervous system development by upregulating the expression levels of vascular genes (flk1 and flt4). The excellent cardiovascular and neurodevelopmental protective ability of L-NANO indicated that high-pressure homogenization is a promising technology for improving the bioactivity of lignin.


Subject(s)
Lignin , Zebrafish , Animals , Zebrafish/metabolism , Lignin/metabolism , Benzhydryl Compounds/metabolism , Oxidative Stress
16.
J Food Sci ; 88(1): 273-292, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36463411

ABSTRACT

Moderately processed surimi products exhibit better nutrient retention and enhanced gels, and the great potential of microwaves application and changes in the way of chopping meat has been reported by previous research. In this study, a systematic analysis of the novel surimi product was made to explore the heat and mass transfer characteristics. A porous media model combining electromagnetic heat and hygroscopic expansion was developed to evaluate this process, and its accuracy has been verified experimentally. It was found that the dielectric characterization of multiphase mixture system has great influence on the results, the complex refractive index mixture equation was used due to its lowest root-mean-square error value. In addition, the effect of moderate processing on microwave heating was examined in terms of porosity changes. However, nonuniform temperature distributions were found in the higher porous samples, especially when the porosity is greater than 0.81. Moreover, the developed model was coupled with the evaluation for gel properties and the results showed the significant effect of moderate crushing on the gel quality during the microwave heating process.


Subject(s)
Heating , Microwaves , Porosity , Hot Temperature , Temperature , Gels
17.
Food Sci Nutr ; 10(12): 4296-4307, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36514778

ABSTRACT

Lipids are important components of surimi products because they enhance the whiteness and flavor of food. The effects of three common types of exogenous lipids on the gel properties of surimi subjected to two different heating methods were investigated in this work, using frozen silver carp (Hypophthalmichthys molitrix) surimi as the raw material. The surimi gels were prepared by two-stage water bath heating or single-stage water bath heating followed by microwave heating. We found that the quality of surimi gels was in the order of lard > chicken fat/soybean oil, which may be associated with polyunsaturated fatty acid content. The surimi gel strength was reduced with an increase in the amount of lipid added. Microwave heating significantly increased the gel strength of surimi containing exogenous lipids when compared to conventional heating. Surimi gels prepared by microwave heating showed more denser protein network microstructures by scanning electron microscopy (SEM), suggesting aggregation of protein molecules. The findings of this study provide a theoretical basis for using microwave heating to generate surimi gels with exogenous lipids.

18.
Front Microbiol ; 13: 1026841, 2022.
Article in English | MEDLINE | ID: mdl-36325022

ABSTRACT

In order to investigate the effects of different areas on intestinal bacterial diversity and body mass regulation in Eothenomys miletus from Hengduan mountain regions, and to explore the community structure and diversity of intestinal microflora and their role in body mass regulation. E. miletus was collected from five areas including Deqin (DQ), Xianggelila (XGLL), Lijiang (LJ), Jianchuan (JC), and Dali (DL), we used 16S rRNA sequencing technology combined with physiological and morphological methods to study the intestinal microbiota diversity, abundance and community structure of the intestinal bacteria in winter, and to explore the influence of geographical factors, physiological indicators including food intake, resting metabolic rate (RMR), non-shivering thermogenesis (NST), neuropeptide Y (NPY), Agouti-Related Protein (AgRP), proopiomelanocortin (POMC), cocaine and amphetamine regulated transcription peptide (CART), and morphological indicators including body mass, body length and other nine indicators on the intestinal microflora diversity in E. miletus. The results showed that there were significant differences in metabolic indexes such as RMR, NST, NPY, AgRP, and morphological indexes such as body length, tail length and ear length among the five regions. Bacterial community in intestinal tract of E. miletus mainly includes three phyla, of which Firmicutes is the dominant phyla, followed by Bacteroidetes and Tenericutes. At the genus level, the dominant bacterial genera were S24-7(UG), Clostridiales (UG), and Lachnospiraceae (UG), etc. α diversity of intestinal microorganisms in DL and JC were significantly different from that in the other three regions. Genera of intestinal microorganisms in DL and JC were also the most. Moreover, Bacteroides, Ruminococcus, and Treponema could affect energy metabolism in E. miletus, which were closely related to the environment in which they lived. All of these results indicated that different areas in Hengduan Mountain had certain effects on the structure of intestinal microbial community in E. miletus, which were responded positively to changes in food abundance and other environmental factors. Furthermore, Firmicutes and Bacteroidetes play an important role in the body mass regulation in E. miletus.

19.
Acta Biochim Biophys Sin (Shanghai) ; 54(10): 1507-1517, 2022 Oct 25.
Article in English | MEDLINE | ID: mdl-36239355

ABSTRACT

Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in various inflammatory diseases. To reveal the impact of MCP-1 during diseases and to develop anti-inflammatory agents, we establish a transgenic mouse line. The firefly luciferase gene is incorporated into the mouse genome and driven by the endogenous MCP-1 promoter. A bioluminescence photographing system is applied to monitor luciferase levels in live mice during inflammation, including lipopolysaccharide-induced sepsis, concanavalin A-induced T cell-dependent liver injury, CCl 4-induced acute hepatitis, and liver fibrosis. The results demonstrate that the luciferase signal induced in inflammatory processes is correlated with endogenous MCP-1 expression in mice. Furthermore, the expressions of MCP-1 and the luciferase gene are dramatically inhibited by administration of the anti-inflammatory drug dexamethasone in a septicemia model. Our results suggest that the transgenic MCP-1-Luc mouse is a useful model to study MCP-1 expression in inflammation and disease and to evaluate the efficiency of anti-inflammatory drugs in vivo.


Subject(s)
Anti-Inflammatory Agents , Chemokine CCL2 , Mice , Animals , Chemokine CCL2/genetics , Anti-Inflammatory Agents/pharmacology , Mice, Transgenic , Inflammation/genetics , Luciferases/genetics
20.
FASEB J ; 36(11): e22602, 2022 11.
Article in English | MEDLINE | ID: mdl-36250925

ABSTRACT

Chronic inflammation is one of the definite factors leading to the occurrence and development of tumors, including prostate cancer (PCa). The androgen receptor (AR) pathway is essential for PCa tumorigenesis and inflammatory response. However, little is known about the AR-regulated NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome pathway in human PCa. In this study, we explored the expression of inflammatory cytokine and AR in high-grade PCa and observed that NLRP3 inflammasome-associated genes were upregulated in high-grade PCa compared with that in low-grade PCa and benign prostatic hyperplasia and were associated with AR expression. In addition, we identified circAR-3-a circRNA derived from the AR gene-which is involved in the AR-regulated inflammatory response and cell proliferation by activating the NLRP3 inflammatory pathway. While circAR-3 overexpression promoted cell proliferation and the inflammatory response, its depletion induced opposite effects. Mechanistically, we noted that circAR-3 mediated the acetylation modification of NLRP3 by KAT2B and then promoted NLRP3 inflammasome complex subcellular distribution and assembly. Disturbing NLRP3 acetylation or blocking inflammasome assembly with an inhibitor suppressed the progression of PCa xenograft tumors. Our findings provide the first evidence that targeting NLRP3 acetylation or inflammasome assembly may be effective in inhibiting PCa progression.


Subject(s)
Prostatic Neoplasms , Receptors, Androgen , Acetylation , Cytokines/metabolism , Humans , Inflammasomes/genetics , Inflammasomes/metabolism , Male , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Prostatic Neoplasms/metabolism , RNA, Circular , Receptors, Androgen/genetics , Receptors, Androgen/metabolism
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