Marine Drugs最新文献_第8页

Antimicrobial and Antibiofilm Activity of Marine Streptomyces sp. NBUD24-Derived Anthraquinones Against MRSA. 海洋链霉菌nbud24衍生蒽醌类对MRSA的抗菌及抗膜活性研究

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-25 DOI: 10.3390/md23080298

Yuxin Yang, Zhiyan Zhou, Guobao Huang, Shuhua Yang, Ruoyu Mao, Lijian Ding, Xiao Wang

{"title":"Antimicrobial and Antibiofilm Activity of Marine Streptomyces sp. NBUD24-Derived Anthraquinones Against MRSA.","authors":"Yuxin Yang, Zhiyan Zhou, Guobao Huang, Shuhua Yang, Ruoyu Mao, Lijian Ding, Xiao Wang","doi":"10.3390/md23080298","DOIUrl":"https://doi.org/10.3390/md23080298","url":null,"abstract":"Antimicrobial resistance (AMR) has emerged as a global health crisis, with methicillin-resistant Staphylococcus aureus (MRSA) representing one of the most clinically significant multidrug-resistant pathogens. In this study, three structurally unique anthracycline derivatives-keto-ester (1), 4-deoxy-ε-pyrromycinone (2), and misamycin (3)-were first isolated and characterized from the fermentation broth of the marine-derived Streptomyces tauricus NBUD24. These compounds exhibited notable antibacterial efficacy against MRSA, with minimum inhibitory concentrations (MICs) ranging from 16 to 32 µg/mL. Cytotoxicity assays confirmed their safety profile at therapeutic concentrations. The biofilm formation assay demonstrated that 4-deoxy-ε-pyrromycinone inhibited biofilm formation of MRSA ATCC43300, with an inhibition rate of 64.4%. Investigations of antibacterial mechanisms revealed that these compounds exert antibacterial effects primarily through disruption of bacterial cell wall integrity and destruction of DNA structure. These findings underscore the potential of marine-derived microbial metabolites as promising scaffolds for developing next-generation antimicrobial candidates to combat drug-resistant infections.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 8","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12387178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Salt-Adapted Microorganisms: A Promising Resource for Novel Anti-Cancer Drug Discovery. 适应盐的微生物：发现新的抗癌药物的有前途的资源。

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-24 DOI: 10.3390/md23080296

Longteng Fang, Liping Xu, Marhaba Kader, Tingting Ding, Shiyang Lu, Dong Wang, Amit Raj Sharma, Zhiwei Zhang

{"title":"Salt-Adapted Microorganisms: A Promising Resource for Novel Anti-Cancer Drug Discovery.","authors":"Longteng Fang, Liping Xu, Marhaba Kader, Tingting Ding, Shiyang Lu, Dong Wang, Amit Raj Sharma, Zhiwei Zhang","doi":"10.3390/md23080296","DOIUrl":"https://doi.org/10.3390/md23080296","url":null,"abstract":"Microorganisms serve as a vital source of natural anticancer agents, with many of their secondary metabolites already employed in clinical oncology. In recent years, salt-adapted microbes, including halophilic and halotolerant species from marine, salt lake, and other high-salinity environments, have gained significant attention. Their unique adaptation mechanisms and diverse secondary metabolites offer promising potential for novel anticancer drug discovery. This review consolidated two decades of research alongside current global cancer statistics to evaluate the therapeutic potential of salt-adapted microorganisms. Halophilic and halotolerant species demonstrate significant promise, with their bioactive metabolites exhibiting potent inhibitory effects against major cancer cell lines, particularly in lung and breast cancer. Evidence reveals structurally unique secondary metabolites displaying enhanced cytotoxicity compared to conventional anticancer drugs. Collectively, salt-adapted microorganisms represent an underexplored yet high-value resource for novel anticancer agents, offering potential solutions to chemotherapy resistance and treatment-related toxicity.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 8","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12387818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Oncolytic Vaccinia Virus Expressing Aphrocallistes Vastus Lectin Modulates Hepatocellular Carcinoma Metabolism via ACSS2/TFEB-Mediated Autophagy and Lipid Accumulation. 一种表达促性股凝集素的溶瘤痘苗病毒通过ACSS2/ tfeb介导的自噬和脂质积累调节肝癌代谢。

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-24 DOI: 10.3390/md23080297

Qiang Wang, Simeng Zhou, Yin Wang, Yajun Gao, Yanrong Zhou, Ting Ye, Gongchu Li, Kan Chen

{"title":"An Oncolytic Vaccinia Virus Expressing Aphrocallistes Vastus Lectin Modulates Hepatocellular Carcinoma Metabolism via ACSS2/TFEB-Mediated Autophagy and Lipid Accumulation.","authors":"Qiang Wang, Simeng Zhou, Yin Wang, Yajun Gao, Yanrong Zhou, Ting Ye, Gongchu Li, Kan Chen","doi":"10.3390/md23080297","DOIUrl":"https://doi.org/10.3390/md23080297","url":null,"abstract":"Hepatocellular carcinoma (HCC) remains a therapeutic challenge due to metabolic plasticity and drug resistance. Oncolytic viruses (OVs), such as thymidine kinase-deleted vaccinia virus (oncoVV), selectively lyse tumors while stimulating antitumor immunity, however, their metabolic interplay with cancer cells is poorly understood. Here, we engineered an oncoVV-expressing Aphrocallistes vastus lectin (oncoVV-AVL) and uncovered its unique ability to exploit the ACSS2/TFEB axis, driving metabolic competition in HCC. In vitro, oncoVV-AVL triggered cell autophagy and lipid accumulation (3.4-5.7-fold upregulation of FASN and ACC1) while suppressing glucose uptake (41-63% higher extracellular glucose and 33-34% reduced lactate). Mechanistically, oncoVV-AVL upregulated acetyl-CoA synthetase 2 (ACSS2), promoting its nuclear translocation and interaction with transcription factor EB (TFEB) to concurrently activate lipogenesis and autophagic flux. The pharmacological inhibition of ACSS2 abolished these effects, confirming its central role. In vivo, oncoVV-AVL suppressed tumor growth while inducing lipid deposition (2-fold triglyceride increase), systemic hypoglycemia (42% glucose reduction), and autophagy activation (elevated LC3B-II/I ratios). This study establishes ACSS2 as a metabolic checkpoint in OV therapy, providing a rationale for combining oncolytic virotherapy with metabolic modulators in HCC.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 8","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12387248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel 3D-Printed Replica Plate Device Ensures High-Throughput Antibacterial Screening of Halophilic Bacteria. 新型3d打印复制板设备确保高通量抗菌筛选嗜盐细菌。

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-23 DOI: 10.3390/md23080295

Kaloyan Berberov, Nikolina Atanasova, Nikolay Krumov, Boryana Yakimova, Irina Lazarkevich, Stephan Engibarov, Tsvetozara Damyanova, Ivanka Boyadzhieva, Lyudmila Kabaivanova

{"title":"Novel 3D-Printed Replica Plate Device Ensures High-Throughput Antibacterial Screening of Halophilic Bacteria.","authors":"Kaloyan Berberov, Nikolina Atanasova, Nikolay Krumov, Boryana Yakimova, Irina Lazarkevich, Stephan Engibarov, Tsvetozara Damyanova, Ivanka Boyadzhieva, Lyudmila Kabaivanova","doi":"10.3390/md23080295","DOIUrl":"https://doi.org/10.3390/md23080295","url":null,"abstract":"Antibiotic resistance is one of the most significant public health issues today. As a consequence, there is an urgent need for novel classes of antibiotics. This necessitates the development of highly efficient screening methods for the rapid identification of antibiotic-producing bacteria. Here, we describe a new method for high-throughput screening of antimicrobial compounds (AMC) producing halophilic bacteria. Our methodology used a newly designed 3D-printed Petri plate replicator used for drop deposition and colony replication. We employed this device in combination with a modified agar overlay assay to screen more than 7400 bacterial colonies. A total of 54 potential AMC producers were discovered at a success rate of 0.7%. Although 40% of them lost their antibacterial activity during the secondary screening, 22 strains retained inhibitory activity and were able to suppress the growth of one or more safe relatives of the ESKAPE group pathogens. The ethyl acetate extract from the most potent strain, Virgibacillus salarius POTR191, demonstrated moderate antibacterial activity against Enterococcus faecalis, Acinetobacter baumanii, and Staphylococcus epidermidis with minimal inhibitory concentrations of 128 μg/mL, 128 μg/mL, and 512 μg/mL, respectively. We propose that our replica plate assay could be used for target-based antimicrobial screening of various extremophilic bacteria.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 8","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12387310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Isolation and Purification of Novel Antioxidant Peptides from Mussel (Mytilus edulis) Prepared by Marine Bacillus velezensis Z-1 Protease. 海洋芽孢杆菌Z-1蛋白酶制备贻贝新型抗氧化肽的分离纯化。

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-23 DOI: 10.3390/md23080294

Jing Lu, Pujing Shi, Yutian Cao, Bingxin Shi, Huilin Shen, Shuai Zhao, Yuchen Gao, Huibing Chi, Lei Wang, Yawei Shi

{"title":"Isolation and Purification of Novel Antioxidant Peptides from Mussel (Mytilus edulis) Prepared by Marine Bacillus velezensis Z-1 Protease.","authors":"Jing Lu, Pujing Shi, Yutian Cao, Bingxin Shi, Huilin Shen, Shuai Zhao, Yuchen Gao, Huibing Chi, Lei Wang, Yawei Shi","doi":"10.3390/md23080294","DOIUrl":"https://doi.org/10.3390/md23080294","url":null,"abstract":"Mussels are nutrient-rich but perishable, resulting in substantial resource loss. A protease-producing strain (Bacillus velezensis Z-1, Mytilus edulis) isolated from marine sludge was used to hydrolyze mussels, producing Y-1, a hydrolysate with antioxidant activity. In this study, ultrafiltration, gel chromatography, and LC-MS/MS were employed to isolate and identify bioactive peptides from the hydrolysate. The results revealed that the hydrolysate exhibited antioxidant activity, pancreatic cholesterol esterase inhibitory activity, pancreatic lipase inhibitory activity, and α-glucosidase inhibitory activity. Molecular docking using AutoDock Tools 1.5.6 was performed to analyze the interactions of peptides with CD38 and Keap1, leading to the identification of five potentially bioactive peptides: VPPFY, IMLFP, LPFLF, FLPF, and FPRIM. These peptides formed hydrogen bonds and hydrophobic interactions with CD38 and Keap1, demonstrating strong DPPH radical scavenging and superoxide anion radical scavenging capacities. This study highlights the multifunctional bioactive potential of these peptides, offering insights into their therapeutic applications. The findings provide a novel approach for the effective utilization of mussel resources and highlight their potential application value in the development of functional foods.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 8","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12387240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioactive Peptides Derived from Tuna: Screening, Extraction, Bioactivity, and Mechanism of Action. 金枪鱼生物活性肽：筛选、提取、生物活性和作用机制。

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-21 DOI: 10.3390/md23070293

Jing-An Cheng, Di Wang, Gang Yu, Shengjun Chen, Zhenhua Ma, Ya Wei, Xue Zhao, Chunsheng Li, Yueqi Wang, Yi Zhang, Rong Cao, Yongqiang Zhao

{"title":"Bioactive Peptides Derived from Tuna: Screening, Extraction, Bioactivity, and Mechanism of Action.","authors":"Jing-An Cheng, Di Wang, Gang Yu, Shengjun Chen, Zhenhua Ma, Ya Wei, Xue Zhao, Chunsheng Li, Yueqi Wang, Yi Zhang, Rong Cao, Yongqiang Zhao","doi":"10.3390/md23070293","DOIUrl":"10.3390/md23070293","url":null,"abstract":"Peptides play a crucial role in the development of pharmaceuticals and functional foods. Multiple studies have shown that natural bioactive peptides possess antioxidant, antihypertensive, anti-tumor, and anti-inflammatory activities. Marine bioactive peptides, especially those sourced from fish, constitute a substantial reservoir of these molecules. Although considerable research has been undertaken on fish-derived peptides, studies specifically concerning those from tuna are limited. Tuna, a marine fish of high nutritional value, generates substantial by-product waste during fishing and processing. Therefore, it is essential to conduct an evaluation of the advancements in study on tuna-derived active peptides and to offer a perspective on the direction of future investigations. This review integrates prospective bioactive peptides derived from tuna and reports contemporary strategies for their investigation, including extraction, purification, screening, identification, and activity evaluation procedures, including Yeast Surface Display (YSD) and molecular docking. This review seeks to promote the continued investigation and application of bioactive peptides derived from tuna.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12298924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Marine-Derived Steroid from Rhodococcus sp., 3,12-Dioxochola-4,6-dien-24-oic Acid, Enhances Skin Re-Epithelialization and Tissue Repair. 一种从红球菌中提取的海洋类固醇，3,12-二氧胆碱-4,6-二烯-24-羟基酸，促进皮肤再上皮化和组织修复。

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-19 DOI: 10.3390/md23070292

Mücahit Varlı, Hui Tan, Chaeyoung Lee, Jeongyun Lee, Ji Young Lee, Jeong-Hyeon Kim, Songyi Lee, Hangun Kim, Sang-Jip Nam

{"title":"A Marine-Derived Steroid from Rhodococcus sp., 3,12-Dioxochola-4,6-dien-24-oic Acid, Enhances Skin Re-Epithelialization and Tissue Repair.","authors":"Mücahit Varlı, Hui Tan, Chaeyoung Lee, Jeongyun Lee, Ji Young Lee, Jeong-Hyeon Kim, Songyi Lee, Hangun Kim, Sang-Jip Nam","doi":"10.3390/md23070292","DOIUrl":"10.3390/md23070292","url":null,"abstract":"The discovery of bioactive natural compounds from microbes holds promise for regenerative medicine. In this study, we identified and characterized a steroid-like compound, 3,12-dioxochola-4,6-dien-24-oic acid (DOCDA), from a crude extract of Rhodococcus sp. DOCDA significantly promoted wound healing by enhancing HaCaT cell invasion and migration. It upregulated key growth factors (EGF, VEGF-A, IGF, TGF-β, and HGF), indicating the activation of regenerative signaling. Additionally, DOCDA increased the expression of genes related to focal adhesion and cytoskeletal regulation (ITGB1, ITGA4, FAK, SRC, RHOA, CDC42, RAC1, and paxillin), supporting enhanced cellular motility and remodeling. Notably, DOCDA promoted stem-like properties in HaCaT cells, as shown by increased spheroid formation and elevated levels of the stemness markers ALDH1 and CD44. Target prediction and molecular docking identified the glucocorticoid receptor (GR) as the primary target of DOCDA, with a docking score of -7.7 kcal/mol. Network and pathway enrichment analysis revealed that GR-linked pathways were significantly associated with wound healing, including steroid hormone signaling, inflammation, immune responses, and cell migration. In vivo, the topical application of DOCDA led to over 70% wound closure in mice by day 5. These findings suggest that DOCDA is a steroid-like compound that accelerates wound healing and may serve as a potential agent in regenerative therapy.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12299624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative Quantitative Proteomic Analysis of High and Low Toxin-Producing Karenia brevis Strains Reveals Differences in Polyketide Synthase Abundance and Redox Status of the Proteome. 高产和低产毒短弧菌的蛋白质组学比较定量分析揭示了蛋白质组中聚酮合成酶丰度和氧化还原状态的差异。

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-17 DOI: 10.3390/md23070291

Kathleen S Rein, Ricardo Colon, Carlos R Romagosa, Nicholas R Ohnikian, Kirstie T Francis, Samuel R Rein

{"title":"Comparative Quantitative Proteomic Analysis of High and Low Toxin-Producing Karenia brevis Strains Reveals Differences in Polyketide Synthase Abundance and Redox Status of the Proteome.","authors":"Kathleen S Rein, Ricardo Colon, Carlos R Romagosa, Nicholas R Ohnikian, Kirstie T Francis, Samuel R Rein","doi":"10.3390/md23070291","DOIUrl":"10.3390/md23070291","url":null,"abstract":"To identify differentially abundant polyketide synthases (PKSs) and to characterize the biochemical consequences of brevetoxin biosynthesis, bottom-up, TMT-based quantitative proteomics and redox proteomics were conducted to compare two strains of the Florida red tide dinoflagellate Karenia brevis, which differ significantly in their brevetoxin content. Forty-eight PKS enzymes potentially linked to brevetoxin production were identified, with thirty-eight showing up to 16-fold higher abundance in the high-toxin strain. A pronounced shift toward a more oxidized redox state was observed in this strain's proteome. Notably, 25 antioxidant-related proteins were significantly elevated, including alternative oxidase (AOX), which increased by 17-fold. These results elucidate the cellular consequences of toxin biosynthesis in K. brevis, offer new leads for the study of brevetoxin biosynthesis, and suggest a novel red tide mitigation approach targeting high toxin-producing strains.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12300183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Novel Diketopiperazine Derivative, Compound 5-3, Selectively Inhibited the Proliferation of FLT3-ITD Mutant Acute Myeloid Leukemia (AML) Cells. 新型二酮哌嗪衍生物化合物5-3选择性抑制FLT3-ITD突变型急性髓系白血病（AML）细胞的增殖。

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-16 DOI: 10.3390/md23070289

Shijie Bi, Yating Cao, Shiyuan Fang, Yanyan Chu, Zixuan Zhang, Meng Li, Rilei Yu, Jinbo Yang, Yu Tang, Peiju Qiu

{"title":"The Novel Diketopiperazine Derivative, Compound 5-3, Selectively Inhibited the Proliferation of FLT3-ITD Mutant Acute Myeloid Leukemia (AML) Cells.","authors":"Shijie Bi, Yating Cao, Shiyuan Fang, Yanyan Chu, Zixuan Zhang, Meng Li, Rilei Yu, Jinbo Yang, Yu Tang, Peiju Qiu","doi":"10.3390/md23070289","DOIUrl":"10.3390/md23070289","url":null,"abstract":"The internal tandem duplication mutation of FMS-like tyrosine kinase 3 (FLT3-ITD) is associated with high recurrence and mortality rates in acute myeloid leukemia (AML), making it a critical target for anti-AML therapies. Plinabulin is a diketopiperazines derivative that exhibits extensive anti-cancer potency by targeting β-tubulin. We designed and synthesized a novel FLT3 inhibitor, namely 5-3, based on the structure of plinabulin and evaluated its effect on FLT3-ITD mutant AML cells. The results indicated that 5-3 potently and selectively inhibits the growth of mutant FLT3-expressingleukemia cells, and had no effect on FLT3 wide-type cancer cells, suggesting the antiproliferative activity of 5-3 depends highly on FLT3-ITD expression. Mechanically, 5-3 significantly suppressed the phosphorylation of FLT3 signaling pathway, including STAT5, Erk and Akt. Moreover, the efficiency of compound 5-3 is not associated with Plinabulin's typical target, β-tubulin. In conclusion, the study identified diketopiperazine derivative as a novel FLT3-ITD selective inhibitor. These results demonstrated that 5-3 might be a drug candidate for the treatment of FLT3-ITD-positive AML.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12299508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chlorella pyrenoidosa Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways. 小球藻核核多糖CPP-3a通过TLR4/2-MyD88-NF-κB/p38 MAPK信号通路促进巨噬细胞M1极化

IF 5.4 2区医学

Marine Drugs Pub Date : 2025-07-16 DOI: 10.3390/md23070290

Yihua Pi, Qingxia Yuan, Shaoting Qin, Chundie Lan, Qingdong Nong, Chenxia Yun, Haibo Tang, Jing Leng, Jian Xiao, Longyan Zhao, Lifeng Zhang

{"title":"Chlorella pyrenoidosa Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways.","authors":"Yihua Pi, Qingxia Yuan, Shaoting Qin, Chundie Lan, Qingdong Nong, Chenxia Yun, Haibo Tang, Jing Leng, Jian Xiao, Longyan Zhao, Lifeng Zhang","doi":"10.3390/md23070290","DOIUrl":"10.3390/md23070290","url":null,"abstract":"The immunomodulatory polysaccharide CPP-3a, purified from Chlorella pyrenoidosa, was investigated for its effects on RAW264.7 macrophages and underlying mechanisms, revealing that CPP-3a significantly enhanced phagocytic capacity and nitric oxide production while upregulating pro-inflammatory cytokines TNF-α and IL-6 and elevating the co-stimulatory molecule CD86, collectively driving robust M1 polarization. Mechanistically, TLR4-, TLR2-specific inhibitors, and TLR4-knockout cells confirmed TLR4 as the primary receptor for CPP-3a, with TLR2 playing a secondary role in cytokine modulation. CPP-3a activated NF-κB and p38 MAPK signaling pathways via the MyD88-dependent pathway, evidenced by phosphorylation of NF-κB/p65 with its nuclear translocation and increased phosphorylation of p38 MAPK, with these signaling activations further validated by specific pathway inhibitors that abolished M1 polarization phenotypes. Collectively, CPP-3a emerges as a potent TLR4-targeted immunomodulator with adjuvant potential for inflammatory and infectious diseases.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12299851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0