Current Issues in Molecular Biology最新文献

{"title":"Acidic Microenvironment Enhances Cisplatin Resistance in Bladder Cancer via Bcl-2 and XIAP.","authors":"Kaede Hiruma, Vladimir Bilim, Akira Kazama, Yuko Shirono, Masaki Murata, Yoshihiko Tomita","doi":"10.3390/cimb47010043","DOIUrl":"10.3390/cimb47010043","url":null,"abstract":"<p><p>Cisplatin (CDDP) remains a key drug for patients with advanced bladder cancer (BC), despite the emergence of new therapeutic agents; thus, the identification of factors contributing to CDDP treatment resistance is crucial. As acidity of the tumor microenvironment has been reported to be associated with treatment resistance and poor prognosis across various cancer types, our objectives in this study were to investigate the effects of an acidic environment on BC cells and elucidate the mechanisms behind CDDP resistance. Our findings show that BC cells cultured under acidic conditions developed cisplatin resistance as acidity increased. Notably, CDDP administered to BC cells in a pH 6.0 environment required double the concentration, compared to those in a pH 7.5 environment, to achieve equivalent toxicity. Using chloroquine and navitoclax, we identified the involvement of the Bcl-2 and LC3B pathways in the acquisition of CDDP resistance under acidic conditions. A Western blot analysis revealed that the activations of Bcl-2 and XIAP expression appear to inhibit both apoptotic and autophagic cell death. Taken together, these results suggest that alleviating the acidity of the tumor microenvironment in clinical settings might enhance BC sensitivity to CDDP.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notoginsenoside R1 Attenuates H/R Injury in H9c2 Cells by Maintaining Mitochondrial Homeostasis.","authors":"Yuanbo Xu, Piao Wang, Ting Hu, Ke Ning, Yimin Bao","doi":"10.3390/cimb47010044","DOIUrl":"10.3390/cimb47010044","url":null,"abstract":"<p><p>Mitochondrial homeostasis is crucial for maintaining cellular energy production and preventing oxidative stress, which is essential for overall cellular function and longevity. Mitochondrial damage and dysfunction often occur concomitantly in myocardial ischemia-reperfusion injury (MIRI). Notoginsenoside R1 (NGR1), a unique saponin from the traditional Chinese medicine Panax notoginseng, has been shown to alleviate MIRI in previous studies, though its precise mechanism remains unclear. This study aimed to elucidate the mechanisms of NGR1 in maintaining mitochondrial homeostasis in hypoxia/reoxygenation (H/R) H9c2 cells. The results showed that NGR1 pretreatment effectively increased cell survival rates post-H/R, reduced lactate dehydrogenase (LDH) leakage, and mitigated cell damage. Further investigation into mitochondria revealed that NGR1 alleviated mitochondrial structural damage, improved mitochondrial membrane permeability transition pore (mPTP) persistence, and prevented mitochondrial membrane potential (Δψm) depolarization. Additionally, NGR1 pretreatment enhanced ATP levels, increased the activity of mitochondrial respiratory chain complexes I-V after H/R, and reduced excessive mitochondrial reactive oxygen species (mitoROS) production, thereby protecting mitochondrial function. Further analysis indicated that NGR1 upregulated the expression of mitochondrial biogenesis-related proteins (PGC-1α, Nrf1, Nrf2) and mitochondrial fusion proteins (Opa1, Mfn1, Mfn2), while downregulating mitochondrial fission proteins (Fis1, Drp1) and reducing mitochondrial autophagy (mitophagy) levels, as well as the expression of mitophagy-related proteins (Pink1, Parkin, BNIP3) post-H/R. Therefore, this study showed that NGR1 can maintain mitochondrial homeostasis by regulating mitophagy, mitochondrial fission-fusion dynamics, and mitochondrial biogenesis, thereby alleviating H9c2 cell H/R injury and protecting cardiomyocytes.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Strong Inhibition of Pancreatic Lipase by Selected Indonesian Medicinal Plants as Anti-Obesity Agents.","authors":"Min Rahminiwati, Dyah Iswantini, Trivadila, Rut Novalia Rahmawati Sianipar, Rani Melati Sukma, Susi Indariani, Anggia Murni","doi":"10.3390/cimb47010039","DOIUrl":"10.3390/cimb47010039","url":null,"abstract":"<p><p>Obesity is characterized by the accumulation of excessive fat, potentially leading to degenerative diseases. Pancreatic lipase, an enzyme responsible for converting 50-70% of dietary fat into monoglycerides, free fatty acids, and various other smaller molecules, plays a crucial role in fat metabolism. Therefore, this study aimed to review selected Indonesian medicinal plants with the potential to inhibit the activity of the pancreatic lipase enzyme. The results showed that kunci pepet (<i>Kaempferiae angustifolia</i> Rosc.), asam gelugur (<i>Garcinia atroviridis</i>), temulawak (<i>Curcuma xanthorrhiza</i>), jombang (<i>Taraxacum officinale</i> F. H. Wigg), pegagan (<i>Centella asiatica</i>), and pala (<i>Myristica fragrans</i>) had strong inhibitory effects, exceeding 50% for both in vitro and in vivo studies. Therefore, further studies are needed to explore the potential of these medicinal plants as anti-obesity treatments.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First Report on Microbial-Derived Polydeoxyribonucleotide: A Sustainable and Enhanced Alternative to Salmon-Based Polydeoxyribonucleotide.","authors":"Doobyeong Chae, Sae-Woong Oh, Yoon-Seo Choi, Dae-Jung Kang, Chun-Woong Park, Jongsung Lee, Won-Sang Seo","doi":"10.3390/cimb47010041","DOIUrl":"10.3390/cimb47010041","url":null,"abstract":"<p><p>Polydeoxyribonucleotide (PDRN) has emerged as a potent bioactive compound with proven efficacy in wound healing, tissue regeneration, and anti-inflammatory applications and is predominantly derived from salmonid gonads. However, this study presents a groundbreaking advancement by successfully extracting and characterizing PDRN from microbial sources, specifically <i>Lactobacillus rhamnosus</i>, marking the first report to utilize microbial-, biome-, or <i>Lactobacillus</i>-derived PDRN (L-PDRN). The findings demonstrate the enhanced biological properties of L-PDRN over traditional salmon-derived PDRN across several assays. L-PDRN exhibited superior antioxidant activity, with significantly higher SOD-like and DPPH radical scavenging activities compared to PDRN, particularly at higher concentrations. In wound-healing assays, L-PDRN demonstrated superior efficacy in promoting cell migration and wound closure, even under inflammatory conditions induced by tumor necrosis factor (TNF-α). Additionally, L-PDRN demonstrated the potential for enhanced immunostimulatory effects under non-inflammatory conditions while maintaining anti-inflammatory properties under lipopolysaccharide (LPS) stimulation. Electrophoretic analysis revealed that L-PDRN consists of smaller DNA fragments (under 100 bp) compared to salmon-derived PDRN (200-800 bp), suggesting greater bioavailability and skin absorption. Mechanistic studies confirmed that L-PDRN activates the focal adhesion kinase (FAK) and protein kinase B (AKT) signaling pathway through the A2A receptor, similar to PDRN, while also engaging alternative pathways for p38 and ERK phosphorylation, highlighting its signaling versatility. This study underscores the potential of L-PDRN as a multifunctional and sustainable alternative to salmon-derived PDRN, offering enhanced bioactivity, scalability, and environmental benefits. The novel approach of utilizing microbial-derived PDRN opens new avenues for therapeutic applications in oxidative stress management, tissue regeneration, and immune modulation, paving the way for a paradigm shift in PDRN sourcing and functionality.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD40 Ligand Potentiates Immunogenecity of <i>Mycoplasma pneumoniae</i> Subunit Vaccine Candidate in a Murine Model.","authors":"Jinqi Shu, Gaojian Li, Jianhong Shu, Huapeng Feng, Yulong He","doi":"10.3390/cimb47010037","DOIUrl":"10.3390/cimb47010037","url":null,"abstract":"<p><p><i>Mycoplasma hyopneumoniae</i> (Mhp) infection severely affects the daily weight gain and feed-to-meat ratio of pigs, while secondary infections with other pathogens can further lead to increased mortality, causing significant economic losses to the pig industry. CD40L is a molecular adjuvant that enhances the cellular and humoral immune responses to vaccines. In this study, the CD40L peptide was fused to the C-terminus of the chimeric P97R1P46P42 protein by genetic engineering using the pFastBac Dual vector. The recombinant chimeric protein P97R1P46P42 and its fusion P97R1P46P42-CD40L were expressed in Sf9 cells and purified. Mice were immunized with P97R1P46P42 or its fusion protein. Seppic ISA 201 emulsified protein, conventional Mhp vaccine and PBS control groups were included. Immunogenecity was assessed by specific IgG antibody response, splenic lymphocyte proliferation, and cytokine IL-4 and IFN-γ levels. We found that CD40L fusion significantly enhanced specific antibody response, lymphocyte proliferation and IL-4 level in the immunized mouse sera as compared to the P97R1P46P42 or conventional vaccine group. This study provides clear evidence that CD40L potentiates the humoral and cellular immune responses to the Mhp chimeric protein P97R1P46P42 in the mouse model. This CD40L-fused chimeric protein could be a MPS subunit vaccine candidate to be tested for its efficacy in pigs in response to challenges with pathogenic <i>Mycoplasma hyopneumoniae</i> strain(s).</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GFAPβ and GFAPδ Isoforms Expression in Mesenchymal Stem Cells, MSCs Differentiated Towards Schwann-like, and Olfactory Ensheathing Cells.","authors":"Nidia Jannette Carrillo González, Gabriela Stefania Reyes Gutierrez, Tania Campos-Ordoñez, Rubén D Castro-Torres, Carlos Beas Zárate, Graciela Gudiño-Cabrera","doi":"10.3390/cimb47010035","DOIUrl":"10.3390/cimb47010035","url":null,"abstract":"<p><p>Olfactory ensheathing cells (OECs) and mesenchymal stem cells (MSCs) differentiated towards Schwann-like have plasticity properties. These cells express the Glial fibrillary acidic protein (GFAP), a type of cytoskeletal protein that significantly regulates many cellular functions, including those that promote cellular plasticity needed for regeneration. However, the expression of GFAP isoforms (α, β, and δ) in these cells has not been characterized. We evaluated GFAP isoforms (α, β, and δ) expression by Polymerase Chain Reaction (PCR) assay in three conditions: (1) OECs, (2) cells exposed to OECs-conditioned medium and differentiated to Schwann-like cells (dBM-MSCs), and (3) MSC cell culture from rat bone marrow undifferentiated (uBM-MSCs). First, the characterization phenotyping was verified by morphology and immunocytochemistry, using p75, CD90, and GFAP antibodies. Then, we found the expression of GFAP isoforms (α, β, and δ) in the three conditions; the expression of the GFAPα (10.95%AUC) and GFAPβ (9.17%AUC) isoforms was predominantly in OECs, followed by dBM-MSCs (α: 3.99%AUC, β: 5.66%AUC) and uBM-MSCs (α: 2.47%AUC, β: 2.97%AUC). GFAPδ isoform has a similar expression in the three groups (OEC: 9.21%AUC, dBM-MSCs: 11.10%AUC, uBM-MSCs: 9.21%AUC). These findings suggest that expression of different GFAPδ and GFAPβ isoforms may regulate cellular plasticity properties, potentially contributing to tissue remodeling processes by OECs, dBM-MSCs, and uBM-MSCs.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant miRNAs for Improved Gene Regulation in a Wide Range of Human Cancers.","authors":"Maksym Zoziuk, Vittorio Colizzi, Pavlo Krysenko, Maurizio Mattei, Roberta Bernardini, Fabio Massimo Zanzotto, Stefano Marini, Dmitri Koroliouk","doi":"10.3390/cimb47010042","DOIUrl":"10.3390/cimb47010042","url":null,"abstract":"<p><p>Determining the relationships between miRNA expression, target genes, and cancer development is critical to cancer research. The possibility of correlating miRNA expression with plant or artificial ones provides prerequisites for cancer treatment. Based on the broad database of human miRNA expression for all cancer types, we grade human miRNAs by their expression level. The identified deficient miRNAs are compared with their target genes for coincidences in their expression directions. The replacement of human miRNAs is proposed to be implemented, using plant miRNAs closest to the human-deficient ones. Such plant substitutes are identified by analyzing the average complementarity of all human under-expressed miRNAs. It was established that the number of downregulated miRNAs is almost 2.5 times greater than that of upregulated miRNAs. There is no significant correlation between the expression of miRNA and genes, implying many other expression regulation mechanisms exist. Working on the organization of experimental verification of the obtained statistical studies, we present significant regularities that provide grounds for considering some plant microRNAs as possible means of compensating for insufficient expression of regulatory microRNAs in humans and animals in a wide range of oncological diseases.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Anticancer Potential of MonoHER (7-Mono-O-(β-Hydroxyethyl)-Rutoside): Mitochondrial-Dependent Apoptosis in HepG2 Cells.","authors":"Chujie Li, Yue Wang, Jian Liang, Guido R M M Haenen, Yonger Chen, Zhengwen Li, Ming Zhang, Ludwig J Dubois","doi":"10.3390/cimb47010036","DOIUrl":"10.3390/cimb47010036","url":null,"abstract":"<p><strong>Background/aim: </strong>Flavonoids are a group of polyphenols, abundantly present in our diet. Although, based on their chemoprotective effects, intake of flavonoids is associated with a high anticancer potential as evidenced in in vitro and in vivo models, the molecular mechanism is still elusive. This study explores the antiproliferative and cytotoxic effects of the semi-synthetic flavonoid MonoHER (7-mono-O-(β-hydroxyethyl)-rutoside) in vitro on cancer cells.</p><p><strong>Materials and methods: </strong>HepG2 liver, MCF7 breast, and H1299 lung cancer cells were grown under ambient conditions with or without MonoHER exposure. CCK8 assay was used to assess cell viability. Apoptosis, JC-1, and mitochondrial mass were determined using flow cytometry and confocal analysis. The effects of monoHER on apoptosis proteins were detected by confocal microscopy analysis and Western blot.</p><p><strong>Results: </strong>It was found that MonoHER can reduce HepG2 cells' and MCF7 cells' viability, but not H1299 cells', and induced apoptosis only in HepG2 cells. MonoHER has the potential to enhance the expression of caspase-9 and caspase-3, to damage mitochondria, and to provoke the release of cytochrome C from the mitochondria.</p><p><strong>Conclusion: </strong>MonoHER can inhibit cell growth and induce apoptosis especially in HepG2 human liver cancer cells by triggering the mitochondrial signal transduction pathway, leading to the release of cytochrome C in the cytoplasm and the subsequent activation of caspase-9 and caspase-3. Future research should further explore MonoHER's mechanism of action, efficacy, and potential for clinical translation.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca <i>Lepidium meyenii</i>.","authors":"Albert Gabriel Turpo-Peqqueña, Sebastian Luna-Prado, Renato Javier Valencia-Arce, Fabio Leonardo Del-Carpio-Carrazco, Badhin Gómez","doi":"10.3390/cimb47010040","DOIUrl":"10.3390/cimb47010040","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant forms of brain cancer. Current therapeutic strategies, including surgery, chemotherapy, and radiotherapy, often fail due to the tumor's ability to develop resistance. The proteins YAP-1 (Yes-associated protein 1) and PARP-1 (Poly-(ADP-ribose)-polymerase-1) have been implicated in this resistance, playing crucial roles in cell proliferation and DNA repair mechanisms, respectively. This study explored the inhibitory potential of natural compounds from <i>Lepidium meyenii</i> (Peruvian Maca) on the YAP-1 and PARP-1 protein systems to develop novel therapeutic strategies for GBM. By molecular dynamics simulations, we identified N-(3-Methoxybenzyl)-(9Z,12Z,15Z)- octadecatrienamide (DK5) as the most promising natural inhibitor for PARP-1 and stearic acid (GK4) for YAP-1. Although synthetic inhibitors, such as Olaparib (ODK) for PARP-1 and Verteporfin (VER) for YAP-1, only VER was superior to the naturally occurring molecule and proved a promising alternative. In conclusion, natural compounds from <i>Lepidium meyenii</i> (Peruvian Maca) offer a potentially innovative approach to improve GBM treatment, complementing existing therapies with their inhibitory action on PARP-1 and YAP-1.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methyl Canthin-6-one-2-carboxylate Inhibits the Activation of the NLRP3 Inflammasome in Synovial Macrophages by Upregulating Nrf2 Expression.","authors":"Yuanyuan Chen, Zongying Zhang, Yuan Yao, Xiaorong Zhou, Yong Ling, Liming Mao, Zhifeng Gu","doi":"10.3390/cimb47010038","DOIUrl":"10.3390/cimb47010038","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an autoimmune disorder that leads to severe cartilage deterioration and synovial impairment in the joints. Previous studies have indicated that the aberrant activation of the NLRP3 inflammasome in synovial macrophages plays a significant role in the pathogenesis of RA and has been regarded as a therapeutic target for the disease. In this study, we synthesized a novel canthin-6-one alkaloid, namely methyl canthin-6-one-2-carboxylate (Cant), and assessed its effects on NLRP3 inflammasome activation in macrophages. Our data reveal that exposure to Cant significantly suppressed the transcription and secretion of multiple pro-inflammatory mediators, including IL-1β, IL-6, IL-18, TNF-α, NO, and COX2, in a dose-dependent manner. These alterations were associated with changes in the activation of various signaling pathways, including NF-kB, MAPK, and PI3K-AKT pathways. Notably, pretreatment with Cant significantly reduced LPS/ATP-induced activation of the NLRP3 inflammasome, as evidenced by the decline in the cleaved forms of IL-1β and caspase-1 in cell culture supernatants of BMDMs. Regarding the mechanisms, our data show that Cant could enhance the expression of Nrf2 in macrophages, which play an inhibitory role in ROS production. Collectively, our data demonstrate that Cant might suppress the activation of the NLRP3 inflammasome by upregulating the production of Nrf2, suggesting that Cant could serve as a candidate for the further development of anti-RA drugs.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}