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Preparation and Vasodilation Mechanism of Angiotensin-I-Converting Enzyme Inhibitory Peptide from Ulva prolifera Protein 从莼菜蛋白中提取血管紧张素-I-转化酶抑制肽的制备方法和血管舒张机制
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-31 DOI: 10.3390/md22090398
Zhiyong Li, Hongyan He, Jiasi Liu, Huiyue Gu, Caiwei Fu, Aurang Zeb, Tuanjie Che, Songdong Shen
{"title":"Preparation and Vasodilation Mechanism of Angiotensin-I-Converting Enzyme Inhibitory Peptide from Ulva prolifera Protein","authors":"Zhiyong Li, Hongyan He, Jiasi Liu, Huiyue Gu, Caiwei Fu, Aurang Zeb, Tuanjie Che, Songdong Shen","doi":"10.3390/md22090398","DOIUrl":"https://doi.org/10.3390/md22090398","url":null,"abstract":"Ulva prolifera, a type of green algae that can be consumed, was utilized in the production of an angiotensin-I converting enzyme (ACE) inhibitory peptide. The protein from the algae was isolated and subsequently hydrolyzed using a neutral protease. The resulting hydrolysate underwent several processes including Sephadex-G100 filtration chromatography, ultrafiltration, HPLC-Q-TOF-MS analysis, ADMET screening, UV spectrum detection test, molecular docking, and molecular dynamic simulation. Then, the ACE inhibitory peptide named KAF (IC50, 0.63 ± 0.26 µM) was identified. The effectiveness of this peptide in inhibiting ACE can be primarily attributed to two conventional hydrogen bonds. Additionally, it could activate endothelial nitric oxide synthase (eNOS) activity to promote the generation of nitric oxide (NO). Additionally, KAF primarily increased the intracellular calcium (Ca2+) level by acting on L-type Ca2+ channel (LTCC) and the ryanodine receptor (RyR) in the endoplasmic reticulum, and completed the activation of eNOS under the mediation of protein kinase B (Akt) signaling pathway. Our study has confirmed that KAF has the potential to be processed into pharmaceutical candidate functions on vasoconstriction.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"12 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and Characterization of a Highly Active Hyaluronan Lyase from Enterobacter asburiae 阿斯布氏肠杆菌高活性透明质酸溶解酶的鉴定和特征描述
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-31 DOI: 10.3390/md22090399
Linjing Zhang, Jiayu Jiang, Wei Liu, Lianlong Wang, Zhiyuan Yao, Heng Li, Jinsong Gong, Chuanli Kang, Lei Liu, Zhenghong Xu, Jinsong Shi
{"title":"Identification and Characterization of a Highly Active Hyaluronan Lyase from Enterobacter asburiae","authors":"Linjing Zhang, Jiayu Jiang, Wei Liu, Lianlong Wang, Zhiyuan Yao, Heng Li, Jinsong Gong, Chuanli Kang, Lei Liu, Zhenghong Xu, Jinsong Shi","doi":"10.3390/md22090399","DOIUrl":"https://doi.org/10.3390/md22090399","url":null,"abstract":"Hyaluronic acid (HA) is a well-known functional marine polysaccharide. The utilization and derivative development of HA are of great interest. Hyaluronan lyase has wide application prospects in the production of HA oligosaccharides and lower molecular weight HA. In this study, a strain of Enterobacter asburiae CGJ001 with high hyaluronan lyase activity was screened from industrial wastewater. This strain exhibited an impressive enzyme activity of 40,576 U/mL after being incubated for 14 h. Whole genome sequencing analysis revealed that E. asburiae CGJ001 contained a cluster of genes involved in HA degradation, transport, and metabolism. A newly identified enzyme responsible for glycosaminoglycan degradation was designated as HylEP0006. A strain of E. coli BL21(DE3)/pET-22b(+)-hylEP0006 was successfully constructed. HylEP0006 exhibited optimal degradation at 40 °C and pH 7.0, showing a high activity of 950,168.3 U/mg. HylEP0006 showed specific activity against HA. The minimum degradation fragment of HylEP0006 was hyaluronan tetrasaccharides, and HylEP0006 could efficiently degrade HA into unsaturated disaccharides (HA2), with HA2 as the final product. These characteristics indicate that HylEP0006 has a potential application prospect for the extraction and utilization of hyaluronic acid.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"20 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antiviral Activity of Chlorophyll Extracts from Tetraselmis sp., a Marine Microalga, Against Zika Virus Infection 海洋微藻 Tetraselmis sp.叶绿素提取物对寨卡病毒感染的抗病毒活性
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-31 DOI: 10.3390/md22090397
Nalae Kang, Eun-A Kim, Areumi Park, Seong-Yeong Heo, Jun-Ho Heo, Won-Kyu Lee, Yong-Kyun Ryu, Soo-Jin Heo
{"title":"Antiviral Activity of Chlorophyll Extracts from Tetraselmis sp., a Marine Microalga, Against Zika Virus Infection","authors":"Nalae Kang, Eun-A Kim, Areumi Park, Seong-Yeong Heo, Jun-Ho Heo, Won-Kyu Lee, Yong-Kyun Ryu, Soo-Jin Heo","doi":"10.3390/md22090397","DOIUrl":"https://doi.org/10.3390/md22090397","url":null,"abstract":"Recent advancements in the large-scale cultivation of Tetraselmis sp. in Korea have enabled year-round production of this marine microalgae. This study explores the potential industrial applications of Tetraselmis sp. biomass by investigating the antiviral properties of its extracts and primary components. The antiviral effects of Tetraselmis sp. extracts were evaluated in Zika virus (ZIKV)-infected cells. Following extensive isolation and purification, the main compounds were characterized using liquid chromatography–mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) analyses. Their antiviral activities were confirmed using in vitro and in silico tests. Tetraselmis sp. extracts reduced infectious viral particles and non-structural protein 1 messenger RNA levels in ZIKV-infected cells without inducing cytotoxicity. Additionally, they modulated the interferon-mediated immune system responses. Tetraselmis sp. extracts are composed of four main chlorophylls: chlorophyll a, chlorin e6-131-152-dimethyl-173-phytyl ester, hydroxychlorophyll a, and hydroxypheophytin a. Among them, chlorophyll a, chlorin e6-131-152-dimethyl-173-phytyl ester, and hydroxypheophytin showed the antiviral activities in ZIKV-infected cells and molecular docking simulations predicted interactions between these chlorophylls and ZIKV. Our findings suggest that Tetraselmis sp. chlorophyll extracts exert antiviral effects against ZIKV and could serve as potential therapeutic candidates against ZIKV infection.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"58 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Two C23-Steroids and a New Isocoumarin Metabolite from Mangrove Sediment-Derived Fungus Penicillium sp. SCSIO 41429 红树林沉积物衍生真菌青霉 SCSIO 41429 的两种 C23 类固醇和一种新的异香豆素代谢物
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-30 DOI: 10.3390/md22090393
Lishan Huang, Chunmei Chen, Jian Cai, Yixin Chen, Yongyan Zhu, Bin Yang, Xuefeng Zhou, Yonghong Liu, Huaming Tao
{"title":"Two C23-Steroids and a New Isocoumarin Metabolite from Mangrove Sediment-Derived Fungus Penicillium sp. SCSIO 41429","authors":"Lishan Huang, Chunmei Chen, Jian Cai, Yixin Chen, Yongyan Zhu, Bin Yang, Xuefeng Zhou, Yonghong Liu, Huaming Tao","doi":"10.3390/md22090393","DOIUrl":"https://doi.org/10.3390/md22090393","url":null,"abstract":"Two new C23-steroids derivatives, cyclocitrinoic acid A (1) and cyclocitrinoic acid B (2), and a new isocoumarin metabolite, (3R,4S)-6,8-dihydroxy-3,4,5-trimethyl-7-carboxamidelisocoumarin (10), together with 12 known compounds (3–9, 11–15) were isolated from the mangrove-sediment fungus Penicillium sp. SCSIO 41429. The structures of the new compounds were comprehensively characterized by 1D and 2D NMR, HRESIMS and ECD calculation. All isolates were evaluated for pancreatic lipase (PL) inhibitory and antioxidant activities. The biological evaluation results revealed that compounds 2, 14 and 15 displayed weak or moderate inhibition against PL, with IC50 values of 32.77, 5.15 and 2.42 µM, respectively. In addition, compounds 7, 12 and 13 showed radical scavenging activities against DPPH, with IC50 values of 64.70, 48.13, and 75.54 µM, respectively. In addition, molecular docking results indicated that these compounds had potential for PL inhibitory and antioxidant activities, which provided screening candidates for antioxidants and a reduction in obesity.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"11 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New Meroterpenes from South China Sea Soft Coral Litophyton brassicum 来自南海软珊瑚 Litophyton brassicum 的新 Meroterpenes
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-30 DOI: 10.3390/md22090392
Xiaoyi Chen, Jiahui Zhang, Jiayu Yang, Bing Li, Te Li, Han Ouyang, Wenhan Lin, Hongyu Hu, Xia Yan, Shan He
{"title":"New Meroterpenes from South China Sea Soft Coral Litophyton brassicum","authors":"Xiaoyi Chen, Jiahui Zhang, Jiayu Yang, Bing Li, Te Li, Han Ouyang, Wenhan Lin, Hongyu Hu, Xia Yan, Shan He","doi":"10.3390/md22090392","DOIUrl":"https://doi.org/10.3390/md22090392","url":null,"abstract":"A chemical investigation of the extracts from the soft coral Litophyton brassicum led to the isolation and identification of four new meroterpenes, brassihydroxybenzoquinone A and B (1 and 2) and brassinaphthoquinone A and B (3 and 4), along with two known related meroterpenes (5 and 6). Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR) spectroscopy, and a comparison with the literature data. All compounds were evaluated for antibacterial activity against six pathogenic bacterial strains and for cytotoxic activity against three cancer cell lines. In the cytotoxic assay, all compounds were inactive at 10 μM against the A549, HeLa, and MDA-MB-231 cell lines. In the antibacterial assay, compounds 1 and 2 exhibited moderate inhibitory activity with minimum inhibitory concentrations (MIC) ranging from 8 to 64 μg/mL.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"25 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ameliorative Effect of Chitosan/Spirulina platensis Ethanolic Extract Nanoformulation against Cyclophosphamide-Induced Ovarian Toxicity: Role of PPAR-γ/Nrf-2/HO-1 and NF-kB/TNF-α Signaling Pathways 壳聚糖/刺五加乙醇提取物纳米制剂对环磷酰胺诱导的卵巢毒性的改善作用:PPAR-γ/Nrf-2/HO-1 和 NF-kB/TNF-α 信号通路的作用
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-30 DOI: 10.3390/md22090395
May Almukainzi, Thanaa A. El-Masry, Hanaa A. Ibrahim, Hebatallah M. Saad, Enas I. El Zahaby, Asmaa Saleh, Maysa M. F. El-Nagar
{"title":"Ameliorative Effect of Chitosan/Spirulina platensis Ethanolic Extract Nanoformulation against Cyclophosphamide-Induced Ovarian Toxicity: Role of PPAR-γ/Nrf-2/HO-1 and NF-kB/TNF-α Signaling Pathways","authors":"May Almukainzi, Thanaa A. El-Masry, Hanaa A. Ibrahim, Hebatallah M. Saad, Enas I. El Zahaby, Asmaa Saleh, Maysa M. F. El-Nagar","doi":"10.3390/md22090395","DOIUrl":"https://doi.org/10.3390/md22090395","url":null,"abstract":"Cyclophosphamide (CP) is an anticancer drug that causes infertility disorders. This study was designed to evaluate a nanoformulation of chitosan with an ethanolic extract from Spirulina platensis in terms of its protection against cyclophosphamide-induced ovarian toxicity. Nine groups of female Wistar rats were randomly assigned as follows: 1: control vehicle, 2: chitosan polymer, 3: telmisartan, 4: Spirulina platensis extract, 5: nanoformulation of the Spirulina platensis, and 6: single injection of CP; groups 7, 8, and 9 received the same treatments as those used in groups 3, 4, and 5, respectively, with a single dose of CP (200 mg/kg, I.P). The results displayed that the CP treatment decreased estradiol, progesterone, anti-mullerian hormone, and GSH content, and it downregulated PPAR-γ, Nrf-2, and HO-1 gene expression. In addition, the CP treatment caused an increase in the FSH, LH, and MDA levels. In the same manner, the protein expression of caspase-3, NF-kB, and TNF-α was upregulated in response to the CP treatment, while PPAR-γ was downregulated in comparison with the control. The rats treated with SPNPs exhibited a substantial reduction in the detrimental effects of oxidative stress and inflammation of the ovarian tissue. This study’s conclusions showed that SPNPs counteracted the effects of CP, preventing the death of ovarian follicles and restoring the gonadotropin hormone balance and normal ovarian histological appearance.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"28 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stonikacidin A, an Antimicrobial 4-Bromopyrrole Alkaloid Containing L-Idonic Acid Core from the Northwestern Pacific Marine Sponge Lissodendoryx papillosa 来自西北太平洋海洋海绵 Lissodendoryx papillosa 的含 L-Idonic Acid 核心的抗菌 4-溴吡咯烷类生物碱 Stonikacidin A
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-30 DOI: 10.3390/md22090396
Kseniya M. Tabakmakher, Tatyana N. Makarieva, Yuri E. Sabutski, Maxim S. Kokoulin, Alexander S. Menshov, Roman S. Popov, Alla G. Guzii, Larisa K. Shubina, Ekaterina A. Chingizova, Artur R. Chingizov, Ekaterina A. Yurchenko, Sergey N. Fedorov, Boris B. Grebnev, Gunhild von Amsberg, Sergey A. Dyshlovoy, Natalia V. Ivanchina, Pavel S. Dmitrenok
{"title":"Stonikacidin A, an Antimicrobial 4-Bromopyrrole Alkaloid Containing L-Idonic Acid Core from the Northwestern Pacific Marine Sponge Lissodendoryx papillosa","authors":"Kseniya M. Tabakmakher, Tatyana N. Makarieva, Yuri E. Sabutski, Maxim S. Kokoulin, Alexander S. Menshov, Roman S. Popov, Alla G. Guzii, Larisa K. Shubina, Ekaterina A. Chingizova, Artur R. Chingizov, Ekaterina A. Yurchenko, Sergey N. Fedorov, Boris B. Grebnev, Gunhild von Amsberg, Sergey A. Dyshlovoy, Natalia V. Ivanchina, Pavel S. Dmitrenok","doi":"10.3390/md22090396","DOIUrl":"https://doi.org/10.3390/md22090396","url":null,"abstract":"Stonikacidin A (1), the first representative of a new class of 4-bromopyrrole alkaloids containing an aldonic acid core, was isolated from the marine sponge Lissodendoryx papillosa. The compound is named in honor of Prof. Valentin A. Stonik, who is one of the outstanding investigators in the field of marine natural chemistry. The structure of 1 was determined using NMR, MS analysis, and chemical correlations. The L-idonic acid core was established by the comparison of GC, NMR, MS, and optical rotation data of methyl-pentaacetyl-aldonates obtained from the hydrolysis products of 1 and standard hexoses. The L-form of the idonic acid residue in 1 was confirmed by GC analysis of pentaacetate of (S)-2-butyl ester of the hydrolysis product from 1 and compared with corresponding derivatives of L- and D-idonic acids. The biosynthetic pathway for stonikacidin A (1) was proposed. The alkaloid 1 inhibited the growth of Staphylococcus aureus and Escherichia coli test strains, as well as affected the formation of S. aureus and E. coli biofilms. Compound 1 inhibited the activity of sortase A. Molecular docking data showed that stonikacidin A (1) can bind with sortase A due to the interactions between its bromine atoms and some amino acid residues of the enzyme.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"13 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bioactive Glial-Derived Neurotrophic Factor from a Safe Injectable Collagen–Alginate Composite Gel Rescues Retinal Photoreceptors from Retinal Degeneration in Rabbits 安全注射型胶原-藻酸盐复合凝胶中的生物活性胶质细胞神经营养因子能拯救兔子视网膜光感受器,使其免于视网膜退化
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-30 DOI: 10.3390/md22090394
Tingyu Hu, Ting Zhou, Rajesh Kumar Goit, Ka Cheung Tam, Yau Kei Chan, Wai-Ching Lam, Amy Cheuk Yin Lo
{"title":"Bioactive Glial-Derived Neurotrophic Factor from a Safe Injectable Collagen–Alginate Composite Gel Rescues Retinal Photoreceptors from Retinal Degeneration in Rabbits","authors":"Tingyu Hu, Ting Zhou, Rajesh Kumar Goit, Ka Cheung Tam, Yau Kei Chan, Wai-Ching Lam, Amy Cheuk Yin Lo","doi":"10.3390/md22090394","DOIUrl":"https://doi.org/10.3390/md22090394","url":null,"abstract":"The management of vision-threatening retinal diseases remains challenging due to the lack of an effective drug delivery system. Encapsulated cell therapy (ECT) offers a promising approach for the continuous delivery of therapeutic agents without the need for immunosuppressants. In this context, an injectable and terminable collagen–alginate composite (CAC) ECT gel, designed with a Tet-on pro-caspase-8 system, was developed as a safe intraocular drug delivery platform for the sustained release of glial-cell-line-derived neurotrophic factor (GDNF) to treat retinal degenerative diseases. This study examined the potential clinical application of the CAC ECT gel, focusing on its safety, performance, and termination through doxycycline (Dox) administration in the eyes of healthy New Zealand White rabbits, as well as its therapeutic efficacy in rabbits with sodium-iodate (SI)-induced retinal degeneration. The findings indicated that the CAC ECT gel can be safely implanted without harming the retina or lens, displaying resistance to degradation, facilitating cell attachment, and secreting bioactive GDNF. Furthermore, the GDNF levels could be modulated by the number of implants. Moreover, Dox administration was effective in terminating gel function without causing retinal damage. Notably, rabbits with retinal degeneration treated with the gels exhibited significant functional recovery in both a-wave and b-wave amplitudes and showed remarkable efficacy in reducing photoreceptor apoptosis. Given its biocompatibility, mechanical stability, controlled drug release, terminability, and therapeutic effectiveness, our CAC ECT gel presents a promising therapeutic strategy for various retinal diseases in a clinical setting, eliminating the need for immunosuppressants.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"61 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chrysomycin A Reshapes Metabolism and Increases Oxidative Stress to Hinder Glioblastoma Progression 金霉素 A 重塑新陈代谢并增加氧化应激,从而阻碍胶质母细胞瘤的进展
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-29 DOI: 10.3390/md22090391
Dong-Ni Liu, Wen-Fang Zhang, Wan-Di Feng, Shuang Xu, Dan-Hong Feng, Fu-Hang Song, Hua-Wei Zhang, Lian-Hua Fang, Guan-Hua Du, Yue-Hua Wang
{"title":"Chrysomycin A Reshapes Metabolism and Increases Oxidative Stress to Hinder Glioblastoma Progression","authors":"Dong-Ni Liu, Wen-Fang Zhang, Wan-Di Feng, Shuang Xu, Dan-Hong Feng, Fu-Hang Song, Hua-Wei Zhang, Lian-Hua Fang, Guan-Hua Du, Yue-Hua Wang","doi":"10.3390/md22090391","DOIUrl":"https://doi.org/10.3390/md22090391","url":null,"abstract":"Glioblastoma represents the predominant and a highly aggressive primary neoplasm of the central nervous system that has an abnormal metabolism. Our previous study showed that chrysomycin A (Chr-A) curbed glioblastoma progression in vitro and in vivo. However, whether Chr-A could inhibit orthotopic glioblastoma and how it reshapes metabolism are still unclear. In this study, Chr-A markedly suppressed the development of intracranial U87 gliomas. The results from airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) indicated that Chr-A improved the abnormal metabolism of mice with glioblastoma. Key enzymes including glutaminase (GLS), glutamate dehydrogenases 1 (GDH1), hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD) were regulated by Chr-A. Chr-A further altered the level of nicotinamide adenine dinucleotide phosphate (NADPH), thus causing oxidative stress with the downregulation of Nrf-2 to inhibit glioblastoma. Our study offers a novel perspective for comprehending the anti-glioma mechanism of Chr-A, highlighting its potential as a promising chemotherapeutic agent for glioblastoma.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"6 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single Amino Acid Substitution in Loop1 Switches the Selectivity of α-Conotoxin RegIIA towards the α7 Nicotinic Acetylcholine Receptor 环路1中的单个氨基酸取代可改变α-芋螺毒素RegIIA对α7烟碱乙酰胆碱受体的选择性
IF 5.4 2区 医学
Marine Drugs Pub Date : 2024-08-29 DOI: 10.3390/md22090390
Jinpeng Yu, Junjie Xie, Yuting Ma, Pengcheng Wei, Panpan Zhang, Zepei Tang, Xiaopeng Zhu, Dongting Zhangsun, Sulan Luo
{"title":"Single Amino Acid Substitution in Loop1 Switches the Selectivity of α-Conotoxin RegIIA towards the α7 Nicotinic Acetylcholine Receptor","authors":"Jinpeng Yu, Junjie Xie, Yuting Ma, Pengcheng Wei, Panpan Zhang, Zepei Tang, Xiaopeng Zhu, Dongting Zhangsun, Sulan Luo","doi":"10.3390/md22090390","DOIUrl":"https://doi.org/10.3390/md22090390","url":null,"abstract":"α-Conotoxins are disulfide-rich peptides obtained from the venom of cone snails, which are considered potential molecular probes and drug leads for nAChR-related disorders. However, low specificity towards different nAChR subtypes restricts the further application of many α-conotoxins. In this work, a series of loop1 amino acid-substituted mutants of α-conotoxin RegIIA were synthesized, whose potency and selectivity were evaluated by an electrophysiological approach. The results showed that loop1 alanine scanning mutants [H5A]RegIIA and [P6A]RegIIA blocked rα7 nAChR with IC50s of 446 nM and 459 nM, respectively, while their inhibition against rα3β2 and rα3β4 subtypes was negligible, indicating the importance of the fifth and sixth amino acid residues for RegIIA’s potency and selectivity. Then, second-generation mutants were designed and synthesized, among which the analogues [H5V]RegIIA and [H5S]RegIIA showed significantly improved selectivity and comparable potency towards rα7 nAChR compared with the native RegIIA. Overall, these findings provide deep insights into the structure–activity relationship of RegIIA, as well as revealing a unique perspective for the further modification and optimization of α-conotoxins and other active peptides.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"112 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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