检索结果-内蒙古大学图书馆

Bile acid- and taurocholate-mediated virulence in AHPND-causing Vibrio parahaemolyticus is independent of the LuxO-OpaR quorum sensing cascade

引用

Aquaculture 2025年 606卷

作者： Kumar, Ramya Lin, Shin-Jen Huang, Chien-Kang Lin, Shih-Shun Wang, Hao-Ching Fagutao, Fernand F. Wang, Han-Ching Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan Taiwan International Center for Scientific Development of Shrimp Aquaculture National Cheng Kung University Tainan Taiwan Department of Engineering Science and Ocean Engineering National Taiwan University Taipei Taiwan Institute of Biotechnology National Taiwan University Taipei Taiwan Graduate Institute of Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan The PhD Program for Translational Medicine College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei Taiwan School of Marine Fisheries and Technology Mindanao State University at Naawan Misamis Oriental Naawan Philippines

Acute hepatopancreatic necrosis disease (AHPND), a prevalent shrimp disease in Southeast Asia, is caused by a specific strain of Vibrio parahaemolyticus (VP) carrying a virulent pVA1 plasmid with PirAB^vp toxin genes. Several host and pathogenic factors affect AHPND pathogenesis. However, quorum sensing (QS), a cell density-based bacterial cell-to-cell communication that regulates virulence factors in Vibrios, mediated mechanisms of AHPND-causing VP are yet to be fully elucidated. Here, we used wild type V. parahaemolyticus, AHPND-causing strain 3HP, along with the 3HP LuxO and/or OpaR QS mutants (ΔopaRΔluxO, ΔopaR, ΔluxO, and luxO^D47E) to investigate the effects of bile acids and taurocholate, dietary supplements given to shrimp to improve growth, on the pathogenicity of AHPND-causing VP. Our results suggest that biofilm formation and PirAB^vp toxin release in AHPND-causing wild type and QS mutants VP strains were induced by bile acids and taurocholate. Furthermore, these dietary supplements affected genes related to flagellar apparatus (MotY, FlhB, FliK, flagellin), bacterial pilus (PilW), biofilm formation (VpsN), bile resistance (OmpT), quorum sensing (LuxR4425, LuxR2865, OpaR, LuxO) and PirAB^vp toxins (PirA, PirB). This suggests that bile acids or taurocholate may affect virulence mechanism of AHPND-causing VP in a LuxO-OpaR QS-independent manner. This study provided insights into host-pathogen interactions and molecular mechanisms of QS in biofilm formation and PirAB^vp toxin production in AHPND-causing VP. © 2025 Elsevier B.V.

关键词： AHPND Bile acids Quorum sensing Taurocholate V. parahaemolyticus

来源：评论

学校读者我要写书评

暂无评论

Potential applications of gene expression profiles obtained from circulating extracellular vesicles in breast cancer

The journal of liquid biopsy

引用

The journal of liquid biopsy 2025年 7卷 100287页

作者： Aritra Gupta Siddharth Bhardwaj Sayan Ghorai Rosina Ahmed Sanjit Agarwal Geetashree Mukherjee Kartiki V Desai Biotechnology Research Innovation Council-National Institute of Biomedical Genomics (BRIC-NIBMG) Kalyani India. Regional Centre for Biotechnology PhD Program India. Tata Medical Centre 14 MAR (DH Block) New Town Rajarhat Kolkata 700160 India.

Background:Liquid biopsy-based biomarkers offer several advantages since they are minimally invasive, can be useful in longitudinal monitoring of the disease and have higher patient compliance. We describe a protocol using minimal volumes of archival and prospective serum/plasma samples to define the RNA contents of EVs and discuss its benefits and limitations. Methods:RNA-seq analysis of matched tumor biopsy, circulating EVs from breast cancer patients (EV-C, n = 26) and healthy donors (EV-H, n = 4) was performed and differentially expressed genes were validated by RT-PCR in a separate series of samples (EV-C, n = 32 and EV-H, n = 22). A total of 84 samples were studied. Results:RNA-seq data from 500 μl serum samples yielded more than 17000 genes, of which 320 were DEGs (adjusted p value ≤ 0.05) between EV-C and EV-H samples. Pathways for Myc V1, reactive oxygen species, angiogenesis, allograft rejection and Interferon regulated genes were over-represented in EV-C samples. Computational deconvolution algorithms for cell signatures identified immune cells such as Th1 and memory T-cells, endothelial cells, and osteoblasts from the stromal compartment as significant. Top 6 genes were validated by qRT-PCR in all samples (n = 84) and they consistently and correctly classified cancer and healthy groups. An independent set of 374 and 640 DEGs could segregate ER positive/ER negative and non-metastatic versus metastatic samples, respectively. EVs from metastatic samples had higher variability in gene expression patterns whereas those from non-metastatic samples showed a better correlation. Conclusion:By using low serum amounts successfully for EV transcriptomics, we demonstrate that a minimally invasive technique could be converted to a microinvasive format. These data lay the foundation for EV RNA based biomarker discovery for segregating breast cancers.

关键词： Diagnosis Liquid biopsy Transcriptomics

来源：评论

学校读者我要写书评

暂无评论

Potential protective role of ACE-inhibitors and AT1 receptor blockers against levodopa-induced dyskinesias:a retrospective case-control study

引用

Neural Regeneration Research 2021年第12期16卷 2475-2478页

作者： Elena Contaldi Luca Magistrelli Anna VMilner Marco Cosentino Franca Marino Cristoforo Comi Movement Disorders Centre Neurology UnitDepartment of Translational MedicineUniversity of Piemonte OrientaleNovaraItaly PhD Program in Medical Sciences and Biotechnology University of Piemonte OrientaleNovaraItaly PhD Program in Clinical and Experimental Medicine and Medical Humanities University of InsubriaVareseItaly Center of Research in Medical Pharmacology University of InsubriaVareseItaly Center for Research in Neuroscience University of InsubriaVareseItaly

Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as *** each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian *** logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs ***-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian *** mean UPDRS part III score was 18.87±7.6 and the median HY stage was *** the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/***,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between *** controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.

关键词： angiotensin-converting enzyme inhibitors AT1 receptor blockers dyskinesias hypertension levodopa motor complications neuroinflammation Parkinson’s disease renin-angiotensin system

来源：评论

学校读者我要写书评

暂无评论

The role of morphology in diagnosing MDS with Non-clonal cytopenias

引用

Leukemia Research 2025年 153卷 107703-107703页

作者： Trotta, Gentiana Elena Santinelli, Enrico Mariani, Sabrina Paciaroni, Katia Caravita di Toritto, Tommaso Cenfra, Natalia Fenu, Susanna Ricci, Paola Maurillo, Luca Moretti, Federico Fabiani, Emiliano Gurnari, Carmelo Voso, Maria Teresa Department of Biomedicine and Prevention University of Rome Tor Vergata Roma Italy Department of Biomedicine and Prevention PhD program in Immunology Molecular Medicine and Applied Biotechnologies Tor Vergata University Roma Italy Fondazione Policlinico Universitario Campus Bio-Medico Via Alvaro del Portillo Roma Italy Hematology Unit Azienda Ospedaliera Universitaria Sant'Andrea Sapienza University Roma Italy UOSD Ematologia ASL Roma 1 Roma Italy Department of Hematology SM Goretti Hospital University Polo Pontino Latina Italy Haematology Department San Giovanni-Addolorata Hospital Roma Italy Department of Biomedicine and Prevention PhD program in Medical-Surgical Biotechnology and Translational Medicine Tor Vergata University Roma Italy UniCamillus-Saint Camillus International University of Health Sciences Roma 00131 Italy Translational Hematology and Oncology Research Department Taussig Cancer Center Cleveland Clinic Cleveland OH United States

Myelodysplastic syndromes/neoplasms (MDS) are a heterogeneous group of blood disorders characterized by distinctive biological and clinical features. Diagnosis typically relies on bone marrow examination and cytogenetic/molecular analysis. However, a small subset of patients lacks detectable cytogenetic or genetic abnormalities, making diagnosis challenging and reliant solely on marrow dysplasia and cytopenia. Here, we conducted a multicenter retrospective study investigating the clinical and hematological features of patients with MDS lacking detectable cytogenetic or molecular alterations. From a cohort of 329 MDS patients who underwent genetic testing at our laboratory of “Diagnostica Avanzata Oncoematologica”, we selected 62 patients presenting with unexplained cytopenia, suspected MDS, and a non-informative cytogenomic profile. Of these, 26 were ultimately diagnosed with alternative conditions such as aplastic anemia, drug/radiation toxicity, multiple myeloma, and others. The patients with non-informative genetic profile had a median age of 60 years and a female predominance (67 %). Autoimmune diseases (AD) were the most frequently observed comorbidities (26 %), and neutropenia was the most common type of cytopenia (56 %), followed by thrombocytopenia (22 %), and anemia (19 %). Most patients had bi-lineage or tri-lineage dysplasia, and had low-risk disease according to IPSS-R and IPSS-M. Only one patient progressed to AML at a median follow-up of 12 months (IQR for the test cohort: 2–25). MDS lacking classical myeloid clonal alteration represent a unique clinical-biological subtype whereby marrow assessment along with a thorough clinical workup is crucial. © 2025 The Authors

关键词： Cytogenetic alterations Cytopenias Dysplasia Myelodysplastic neoplasms Next generation sequencing

来源：评论

学校读者我要写书评

暂无评论

Fate and state transitions during human blood vessel organoid development

引用

Cell 2025年

作者： Nikolova, Marina T. He, Zhisong Seimiya, Makiko Jonsson, Gustav Cao, Wuji Okuda, Ryo Wimmer, Reiner A. Okamoto, Ryoko Penninger, Josef M. Camp, J. Gray Treutlein, Barbara Department of Biosystems Science and Engineering ETH Zurich Basel Switzerland Institute of Molecular Biotechnology of the Austrian Academy of Sciences Vienna Austria Vienna BioCenter PhD Program Doctoral School of the University of Vienna and Medical University of Vienna Vienna 1030 Austria Roche Pharma Research and Early Development Roche Innovation Center Basel Switzerland Department of Medical Genetics Life Science Institute University of British Columbia Vancouver V6T 1Z3 BC Canada Department of Laboratory Medicine Medical University of Vienna Vienna Austria Helmholtz Centre for Infection Research Braunschweig Germany Institute of Human Biology Roche Pharma Research and Early Development Roche Innovation Center Basel Basel Switzerland Biozentrum University of Basel Basel Switzerland

Human blood vessel organoids (hBVOs) have emerged as a system to model human vascular development and disease. Here, we use single-cell multi-omics together with genetic and signaling pathway perturbations to reconstruct hBVO development. Mesodermal progenitors bifurcate into endothelial and mural fates in vitro, and xenografted BVOs acquire definitive arteriovenous endothelial cell specification. We infer a gene regulatory network and use single-cell genetic perturbations to identify transcription factors (TFs) and receptors involved in cell fate specification, including a role for MECOM in endothelial and mural specification. We assess the potential of BVOs to generate organotypic states, identify TFs lacking expression in hBVOs, and find that induced LEF1 overexpression increases brain vasculature specificity. Finally, we map vascular disease-associated genes to hBVO cell states and analyze an hBVO model of diabetes. Altogether, we provide a comprehensive cell state atlas of hBVO development and illuminate the power and limitation of hBVOs for translational research. © 2025 The Authors

关键词： arteriovenous specification human blood vessel organoid human development organoid cell atlas single-cell genomics single-cell perturbation screen

来源：评论

学校读者我要写书评

暂无评论

Discovery of Novel Zoanthamine-Type Alkaloids Derived from Cultured Zoanthus Kuroshio with Prominent Therapeutic Potential Against Osteoporosis

SSRN

引用

SSRN 2025年

作者： Pham, Ngoc-Thac Peng, Bo-Rong Le, Huong-Giang Chen, Yun-Shiuan Huynh, Thanh Hao Chen, Lo-Yun Nguyen, Le Anh Tuan Nguyen, Dang T. Su, Jui-Hsin El-Shazly, Mohamed Lee, Mei-Hsien Lai, Kuei-Hung PhD Program in Clinical Drug Development of Herbal Medicine College of Pharmacy Taipei Medical University Taipei110301 Taiwan Graduate Institute of Pharmacognosy College of Pharmacy Taipei Medical University Taipei110301 Taiwan Graduate Institute of Healthy Industry Technology Research Center for Chinese Herbal Medicine College of Human Ecology Chang Gung University of Science and Technology Taoyuan333324 Taiwan Faculty of Pharmacy Lac Hong University Dongnai Bien Hoa Viet Nam Faculty of Applied Sciences Ton Duc Thang University Ho Chi Minh City Viet Nam National Museum of Marine Biology and Aquarium Pingtung944401 Taiwan Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung804201 Taiwan Department of Pharmacognosy Faculty of Pharmacy Ain-Shams University Organization of African Unity Street Abassia Cairo11566 Egypt Center for Reproductive Medicine and Sciences Taipei Medical University Hospital Taipei110301 Taiwan Traditional Herbal Medicine Research Center Taipei Medical University Hospital Taipei110301 Taiwan

Marine invertebrates are well-established as prolific sources of secondary metabolites, renowned for their remarkable chemical diversity and extensive spectrum of biological activities. Among these, Zoanthus Kuroshio (ZK) has gained significant attention due to its abundant chemical constituents, particularly alkaloids, which exhibit promising bioactivities against osteoporosis. To investigate its therapeutic potential, the extracts of cultured ZK exhibited significant anti-osteoporotic activity in vitro with MG-63 cells, leading to the integration of Global Natural Products Social Molecular Networking (GNPS) to identify fractions containing the highest amounts of alkaloids. Subsequent isolation efforts resulted in the discovery of five novel zoanthamine-type alkaloids: norzoabenzaldehyde (1), norzoazepanol (2), 11-keto-3-acetoxynorzoanthamine (3), 11-hydroxynorzoanthamide B (4), and 11-hydroxyzoanthamide B (5), alongside four previously identified compounds, including norzoanthaminone (6), 3-acetoxynorzoanthamine (7), 3-acetoxyzoanthamine (8), and 3-hydroxynorzoanthamine (9). Structural elucidation of compounds 1, 3, 4, and 5 was achieved using comprehensive spectroscopic analyses, whereas compound 2 required advanced techniques, including time-dependent density functional theory nuclear magnetic resonance (TDDFT-NMR) calculations and comparative analysis of theoretical and experimental electronic circular dichroism (ECD) data, to ascertain its absolute configuration. Bioassays evaluating alkaline phosphatase activity and mineralization demonstrated that compound 9 exhibited significant activity, with an IC50 value of 20 µM. The mechanism by which this compound operates was elucidated through network pharmacology, molecular docking and dynamics simulations, further confirming the stability of interactions between compound 9 and key protein targets, thereby emphasizing its potential as a promising lead compound for osteoporosis therapeutics. © 2025, The Authors. All

关键词： Spectroscopic analysis

来源：评论

学校读者我要写书评

暂无评论

Caffeic acid phenethyl ester suppresses the expression of androgen receptor variant 7 via inhibition of CDK1 and AKT

引用

Cancer Gene Therapy 2024年第6期31卷 807-815页

作者： Kuo, Ying-Yu Huo, Chieh Li, Chia-Yang Chuu, Chih-Pin Institute of Cellular and System Medicine National Health Research Institutes Miaoli County Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Medical Research Kaohsiung Medical University Kaohsiung Taiwan PhD Program for Aging and Graduate Institute of Basic Medical Science China Medical University Taichung City Taiwan Biotechnology Center National Chung Hsing University Taichung City Taiwan Department of Life Sciences National Central University Taoyuan City Taiwan

Androgen receptor (AR) splice variant 7 (AR-V7) is capable to enter nucleus and activate downstream signaling without ligand. AR-V7 assists the tumor growth, cancer metastasis, cancer stemness, and the evolvement of therapy-resistant prostate cancer (PCa). We discovered that caffeic acid phenethyl ester (CAPE) can repress the expression and downstream signaling of AR-V7 in PCa cells. CAPE blocked the gene transcription, nuclear localization, and protein abundance of AR-V7. CAPE inhibited the expression of U2AF65, SF2 and hnRNPF, which were splicing factors for AR-V7 intron. Additionally, CAPE decreased protein stability of AR-V7 and enhanced the proteosome-degradation of AR-V7. We observed that CDK1 and AKT regulated the expression and stability of AR-V7 via phosphorylation of Ser81 and Ser213, respectively. CAPE decreased the expression of CDK1 and AKT. Overexpression of CDK1 restored the abundance of AR-V7 in CAPE-treated PCa cells. Overexpression of AR-V7, AKT or CDK1 rescued the proliferation of PCa cells under CAPE treatment. Intraperitoneal injection of 10 mg/kg CAPE retarded the growth of 22Rv1 xenografts in nude mice and suppressed the protein levels of AR-V7, CDK1 and AKT in 22Rv1 xenografts. Our study provided the rationale of applying CAPE for inhibition of AR-V7 in prostate tumors. (Figure presented.). © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

关键词： Drug development Prostate cancer

来源：评论

学校读者我要写书评

暂无评论

Enhanced IGF-IIRα Expression Exacerbates Lipopolysaccharide-Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation

引用

Environmental Toxicology 2024年第11期39卷 5173-5186页

作者： Boonha, Khwanchit Kuo, Wei-Wen Tsai, Bruce Chi-Kang Hsieh, Dennis Jine-Yuan Lin, Kuan-Ho Lu, Shang-Yeh Kuo, Chia-Hua Yang, Liang-Yo Huang, Chih-Yang Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Faculty of Tropical Medicine Mahidol University Bangkok Thailand Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan PhD Program for Biotechnology Industry China Medical University Taichung Taiwan School of Pharmacy China Medical University Taichung Taiwan Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan Department of Emergency Medicine China Medical University Hospital Taichung Taiwan College of Medicine China Medical University Taichung Taiwan Division of Cardiovascular Medicine Department of Internal Medicine China Medical University Hospital Taichung Taiwan Laboratory of Exercise Biochemistry University of Taipei Taipei Taiwan Institute of Sports Sciences University of Taipei Taipei Taiwan Department of Kinesiology and Health Science College of William and Mary WilliamsburgVA United States School of Physical Education and Sports Science Soochow University Suzhou China Department of Physiology School of Medicine College of Medicine China Medical University Taichung Taiwan Laboratory for Neural Repair China Medical University Hospital Taichung Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan Center of General Education Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology Hualien Taiwan

Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function. © 2024 Wiley Periodicals LLC.

关键词： Heart

来源：评论

学校读者我要写书评

暂无评论

Demethoxymurrapanine, an indole-naphthoquinone alkaloid, inhibits the proliferation of oral cancer cells without major side effects on normal cells

引用

Environmental Toxicology 2024年第3期39卷 1221-1234页

作者： Chuang, Ya-Ting Yen, Ching-Yu Shiau, Jun-Ping Chang, Fang-Rong Duh, Chang-Yih Sung, Ping-Jyun Chen, Kuan-Liang Tsai, Yi-Hong Tang, Jen-Yang Jeng, Jiiang-Huei Sheu, Jyh-Horng Chang, Hsueh-Wei Department of Biomedical Science and Environmental Biology PhD Program in Life Sciences College of Life Science Kaohsiung Medical University Kaohsiung Taiwan School of Dentistry Taipei Medical University Taipei Taiwan Department of Oral and Maxillofacial Surgery Chi-Mei Medical Center Tainan Taiwan Division of Breast Oncology and Surgery Department of Surgery Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung Taiwan Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung Taiwan National Museum of Marine Biology and Aquarium Pingtung Taiwan Department of Pharmacy and Master Program College of Pharmacy and Health Care Tajen University Pingtung Taiwan School of Post-Baccalaureate Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Radiation Oncology Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan School of Dentistry College of Dental Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Dentistry Kaohsiung Medical University Hospital Kaohsiung Taiwan Department of Dentistry National Taiwan University Hospital Taipei Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Taiwan Center for Cancer Research Kaohsiung Medical University Kaohsiung Taiwan

Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in-depth investigation was necessary. This study evaluated the proliferation-modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 μg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9-22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S-G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N-acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer than in normal cells. N-acetylcysteine attenuated all these DEMU-induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells. © 2023 Wiley Periodicals LLC.

关键词： Oxidative stress

来源：评论

学校读者我要写书评

暂无评论

Targeting protein-protein interaction interfaces with antiviral N protein inhibitor in SARS-CoV-2

引用

Biophysical Journal 2024年第4期123卷 478-488页

作者： Hong, Jhen-Yi Lin, Shih-Chao Kehn-Hall, Kylene Zhang, Kai-Min Luo, Shun-Yuan Wu, Hung-Yi Chang, Sui-Yuan Hou, Ming-Hon Institute of Genomics and Bioinformatics and Department of Life Sciences National Chung Hsing University Taichung Taiwan Bachelor Degree Program in Marine Biotechnology College of Life Sciences National Taiwan Ocean University Keelung Taiwan Department of Biomedical Sciences and Pathobiology Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg VA United States Center for Emerging Zoonotic and Arthropod-borne Pathogens Virginia Polytechnic Institute and State University Blacksburg VA United States Department of Chemistry National Chung Hsing University Taichung Taiwan Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University. Taichung Taiwan Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine National Taiwan University Taipei Taiwan PhD Program in Medical Biotechnology National Chung Hsing University Taichung Taiwan Biotechnology Center National Chung Hsing University Taichung Taiwan

Coronaviruses not only pose significant global public health threats but also cause extensive damage to livestock-based industries. Previous studies have shown that 5-benzyloxygramine (P3) targets the Middle East respiratory syndrome coronavirus (MERS-CoV) nucleocapsid (N) protein N-terminal domain (N-NTD), inducing non-native protein-protein interactions (PPIs) that impair N protein function. Moreover, P3 exhibits broad-spectrum antiviral activity against CoVs. The sequence similarity of N proteins is relatively low among CoVs, further exhibiting notable variations in the hydrophobic residue responsible for non-native PPIs in the N-NTD. Therefore, to ascertain the mechanism by which P3 demonstrates broad-spectrum anti-CoV activity, we determined the crystal structure of the SARS-CoV-2 N-NTD:P3 complex. We found that P3 was positioned in the dimeric N-NTD via hydrophobic contacts. Compared with the interfaces in MERS-CoV N-NTD, P3 had a reversed orientation in SARS-CoV-2 N-NTD. The Phe residue in the MERS-CoV N-NTD:P3 complex stabilized both P3 moieties. However, in the SARS-CoV-2 N-NTD:P3 complex, the Ile residue formed only one interaction with the P3 benzene ring. Moreover, the pocket in the SARS-CoV-2 N-NTD:P3 complex was more hydrophobic, favoring the insertion of the P3 benzene ring into the complex. Nevertheless, hydrophobic interactions remained the primary stabilizing force in both complexes. These findings suggested that despite the differences in the sequence, P3 can accommodate a hydrophobic pocket in N-NTD to mediate a non-native PPI, enabling its effectiveness against various CoVs. © 2024 Biophysical Society

关键词：

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：