Journal of Biomedical Science最新文献

{"title":"Correction: Post-translational modifications on the retinoblastoma protein.","authors":"Linbin Zhou, Danny Siu-Chun Ng, Jason C Yam, Li Jia Chen, Clement C Tham, Chi Pui Pang, Wai Kit Chu","doi":"10.1186/s12929-024-01079-6","DOIUrl":"https://doi.org/10.1186/s12929-024-01079-6","url":null,"abstract":"","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"98"},"PeriodicalIF":9.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390889","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}

{"title":"Hijacking host extracellular vesicle machinery by hepatotropic viruses: current understandings and future prospects.","authors":"Yu-De Chu, Mi-Chi Chen, Chau-Ting Yeh, Ming-Wei Lai","doi":"10.1186/s12929-024-01063-0","DOIUrl":"10.1186/s12929-024-01063-0","url":null,"abstract":"<p><p>Recent advances in studies exploring the roles of extracellular vesicles (EVs) in viral transmission and replication have illuminated hepatotropic viruses, such as hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV). While previous investigations have uncovered these viruses' ability to exploit cellular EV pathways for replication and transmission, most have focused on the impacts of exosomal pathways. With an improved understanding of EVs, four main subtypes, including exosomes, microvesicles, large oncosomes, and apoptotic bodies, have been categorized based on size and biogenic pathways. However, there remains a noticeable gap in comprehensive reviews summarizing recent findings and outlining future perspectives for EV studies related to hepatotropic viruses. This review aims to consolidate insights into EV pathways utilized by hepatotropic viruses, offering guidance for the future research direction in this field. By comprehending the diverse range of hepatotropic virus-associated EVs and their role in cellular communication during productive viral infections, this review may offer valuable insights for targeting therapeutics and devising strategies to combat virulent hepatotropic virus infections and the associated incidence of liver cancer.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"97"},"PeriodicalIF":9.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11453063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377854","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}

{"title":"Non-coding RNAs as modulators of radioresponse in triple-negative breast cancer: a systematic review.","authors":"Maria Vitoria Tofolo, Fernanda Costa Brandão Berti, Emanuelle Nunes-Souza, Mayara Oliveira Ruthes, Lucas Freitas Berti, Aline Simoneti Fonseca, Daiane Rosolen, Luciane Regina Cavalli","doi":"10.1186/s12929-024-01081-y","DOIUrl":"10.1186/s12929-024-01081-y","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC), characterized by high invasiveness, is associated with poor prognosis and elevated mortality rates. Despite the development of effective therapeutic targets for TNBC, systemic chemotherapy and radiotherapy (RdT) remain prevalent treatment modalities. One notable challenge of RdT is the acquisition of radioresistance, which poses a significant obstacle in achieving optimal treatment response. Compelling evidence implicates non-coding RNAs (ncRNAs), gene expression regulators, in the development of radioresistance. This systematic review focuses on describing the role, association, and/or involvement of ncRNAs in modulating radioresponse in TNBC. In adhrence to the PRISMA guidelines, an extensive and comprehensive search was conducted across four databases using carefully selected entry terms. Following the evaluation of the studies based on predefined inclusion and exclusion criteria, a refined selection of 37 original research articles published up to October 2023 was obtained. In total, 33 different ncRNAs, including lncRNAs, miRNAs, and circRNAs, were identified to be associated with radiation response impacting diverse molecular mechanisms, primarily the regulation of cell death and DNA damage repair. The findings highlighted in this review demonstrate the critical roles and the intricate network of ncRNAs that significantly modulates TNBC's responsiveness to radiation. The understanding of these underlying mechanisms offers potential for the early identification of non-responders and patients prone to radioresistance during RdT, ultimately improving TNBC survival outcomes.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"93"},"PeriodicalIF":9.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361623","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}

{"title":"Enhancing organoid culture: harnessing the potential of decellularized extracellular matrix hydrogels for mimicking microenvironments.","authors":"Chen Li, Ni An, Qingru Song, Yuelei Hu, Wenzhen Yin, Qi Wang, Yinpeng Le, Wenting Pan, Xinlong Yan, Yunfang Wang, Juan Liu","doi":"10.1186/s12929-024-01086-7","DOIUrl":"https://doi.org/10.1186/s12929-024-01086-7","url":null,"abstract":"<p><p>Over the past decade, organoids have emerged as a prevalent and promising research tool, mirroring the physiological architecture of the human body. However, as the field advances, the traditional use of animal or tumor-derived extracellular matrix (ECM) as scaffolds has become increasingly inadequate. This shift has led to a focus on developing synthetic scaffolds, particularly hydrogels, that more accurately mimic three-dimensional (3D) tissue structures and dynamics in vitro. The ECM-cell interaction is crucial for organoid growth, necessitating hydrogels that meet organoid-specific requirements through modifiable physical and compositional properties. Advanced composite hydrogels have been engineered to more effectively replicate in vivo conditions, offering a more accurate representation of human organs compared to traditional matrices. This review explores the evolution and current uses of decellularized ECM scaffolds, emphasizing the application of decellularized ECM hydrogels in organoid culture. It also explores the fabrication of composite hydrogels and the prospects for their future use in organoid systems.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"96"},"PeriodicalIF":9.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347561","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}

{"title":"CCL5 is essential for axonogenesis and neuronal restoration after brain injury","authors":"Man-Hau Ho, Yih-Jeng Tsai, Chia-Yen Chen, Anastasia Yang, Thierry Burnouf, Yun Wang, Yung-Hsiao Chiang, Barry J. Hoffer, Szu-Yi Chou","doi":"10.1186/s12929-024-01083-w","DOIUrl":"https://doi.org/10.1186/s12929-024-01083-w","url":null,"abstract":"Traumatic brain injury (TBI) causes axon tearing and synapse degradation, resulting in multiple neurological dysfunctions and exacerbation of early neurodegeneration; the repair of axonal and synaptic structures is critical for restoring neuronal function. C-C Motif Chemokine Ligand 5 (CCL5) shows many neuroprotective activities. A close-head weight-drop system was used to induce mild brain trauma in C57BL/6 (wild-type, WT) and CCL5 knockout (CCL5-KO) mice. The mNSS score, rotarod, beam walking, and sticker removal tests were used to assay neurological function after mTBI in different groups of mice. The restoration of motor and sensory functions was impaired in CCL5-KO mice after one month of injury, with swelling of axons and synapses from Golgi staining and reduced synaptic proteins-synaptophysin and PSD95. Administration of recombinant CCL5 (Pre-treatment: 300 pg/g once before injury; or post-treatment: 30 pg/g every 2 days, since 3 days after injury for 1 month) through intranasal delivery into mouse brain improved the motor and sensory neurological dysfunctions in CCL5-KO TBI mice. Proteomic analysis using LC-MS/MS identified that the “Nervous system development and function”-related proteins, including axonogenesis, synaptogenesis, and myelination signaling pathways, were reduced in injured cortex of CCL5-KO mice; both pre-treatment and post-treatment with CCL5 augmented those pathways. Immunostaining and western blot analysis confirmed axonogenesis and synaptogenesis related Semaphorin, Ephrin, p70S6/mTOR signaling, and myelination-related Neuregulin/ErbB and FGF/FAK signaling pathways were up-regulated in the cortical tissue by CCL5 after brain injury. We also noticed cortex redevelopment after long-term administration of CCL5 after brain injury with increased Reelin positive Cajal-Rerzius Cells and CXCR4 expression. CCL5 enhanced the growth of cone filopodia in a primary neuron culture system; blocking CCL5’s receptor CCR5 by Maraviroc reduced the intensity of filopodia in growth cone and also CCL5 mediated mTOR and Rho signalling activation. Inhibiting mTOR and Rho signaling abolished CCL5 induced growth cone formation. CCL5 plays a critical role in starting the intrinsic neuronal regeneration system following TBI, which includes growth cone formation, axonogenesis and synaptogensis, remyelination, and the subsequent proper wiring of cortical circuits. Our study underscores the potential of CCL5 as a robust therapeutic stratagem in treating axonal injury and degeneration during the chronic phase after mild brain injury. ","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"77 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261871","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}

{"title":"Decreased plasma gelsolin fosters a fibrotic tumor microenvironment and promotes chemoradiotherapy resistance in esophageal squamous cell carcinoma","authors":"Chih-Hsiung Hsieh, Pei-Shiuan Ho, Wen-Lun Wang, Fu-Hsuan Shih, Chen-Tai Hong, Pei-Wen Wang, Dar-Bin Shieh, Wei-Lun Chang, Yi-Ching Wang","doi":"10.1186/s12929-024-01078-7","DOIUrl":"https://doi.org/10.1186/s12929-024-01078-7","url":null,"abstract":"Stromal fibrosis is highly associated with therapeutic resistance and poor survival in esophageal squamous cell carcinoma (ESCC) patients. Low expression of plasma gelsolin (pGSN), a serum abundant protein, has been found to correlate with inflammation and fibrosis. Here, we evaluated pGSN expression in patients with different stages of cancer and therapeutic responses, and delineated the molecular mechanisms involved to gain insight into therapeutic strategies for ESCC. Circulating pGSN level in ESCC patients was determined by enzyme-linked immunosorbent assay analysis, and the tissue microarray of tumors was analyzed by immunohistochemistry staining. Cell-based studies were performed to investigate cancer behaviors and molecular mechanisms, and mouse models were used to examine the pGSN-induced tumor suppressive effects in vivo. Circulating pGSN expression is distinctively decreased during ESCC progression, and low pGSN expression correlates with poor therapeutic responses and poor survival. Methylation-specific PCR analysis confirmed that decreased pGSN expression is partly attributed to the hypermethylation of the GSN promoter, the gene encoding pGSN. Importantly, cell-based immunoprecipitation and protein stability assays demonstrated that pGSN competes with oncogenic tenascin-C (TNC) for the binding and degradation of integrin αvβ3, revealing that decreased pGSN expression leads to the promotion of oncogenic signaling transduction in cancer cells and fibroblasts. Furthermore, overexpression of pGSN caused the attenuation of TNC expression and inactivation of cancer-associated fibroblast (CAF), thereby leading to tumor growth inhibition in mice. Our results demonstrated that GSN methylation causes decreased secretion of pGSN, leading to integrin dysregulation, oncogenic TNC activation, and CAF formation. These findings highlight the role of pGSN in therapeutic resistance and the fibrotic tumor microenvironment of ESCC.","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"28 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198700","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}

{"title":"Current landscape of mRNA technologies and delivery systems for new modality therapeutics","authors":"Ruei-Min Lu, Hsiang-En Hsu, Ser John Lynon P. Perez, Monika Kumari, Guan-Hong Chen, Ming-Hsiang Hong, Yin-Shiou Lin, Ching-Hang Liu, Shih-Han Ko, Christian Angelo P. Concio, Yi-Jen Su, Yi-Han Chang, Wen-Shan Li, Han-Chung Wu","doi":"10.1186/s12929-024-01080-z","DOIUrl":"https://doi.org/10.1186/s12929-024-01080-z","url":null,"abstract":"Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases.","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"17 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198701","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}

{"title":"Neuroprotective effects of intranasal extracellular vesicles from human platelet concentrates supernatants in traumatic brain injury and Parkinson's disease models.","authors":"Liling Delila, Ouada Nebie, Nhi Thao Ngoc Le, Kelly Timmerman, Deng-Yao Lee, Yu-Wen Wu, Ming-Li Chou, Luc Buée, Szu-Yi Chou, David Blum, David Devos, Thierry Burnouf","doi":"10.1186/s12929-024-01072-z","DOIUrl":"10.1186/s12929-024-01072-z","url":null,"abstract":"<p><strong>Background: </strong>The burgeoning field of regenerative medicine has significantly advanced with recent findings on biotherapies using human platelet lysates (HPLs), derived from clinical-grade platelet concentrates (PCs), for treating brain disorders. These developments have opened new translational research avenues to explore the neuroprotective effects of platelet-extracellular vesicles (PEVs). Their potential in managing neurodegenerative conditions like traumatic brain injury (TBI) and Parkinson's disease (PD) warrants further exploration. We aimed here to characterize the composition of a PEV preparation isolated from platelet concentrate (PC) supernatant, and determine its neuroprotective potential and neurorestorative effects in cellular and animal models of TBI and PD.</p><p><strong>Methods: </strong>We isolated PEVs from the supernatant of clinical-grade PC collected from healthy blood donors utilizing high-speed centrifugation. PEVs were characterized by biophysical, biochemical, microscopic, and LC-MS/MS proteomics methods to unveil biological functions. Their functionality was assessed in vitro using SH-SY5Y neuronal cells, LUHMES dopaminergic neurons, and BV-2 microglial cells, and in vivo by intranasal administration in a controlled cortical impact (CCI)-TBI model using 8-weeks-old male C57/BL6 mice, and in a PD model induced by MPTP in 5-month-old male C57/BL6 mice.</p><p><strong>Results: </strong>PEVs varied in size from 50 to 350 nm, predominantly around 200 nm, with concentrations ranging between 10¹⁰ and 10¹¹/mL. They expressed specific platelet membrane markers, exhibited a lipid bilayer by cryo-electron microscopy and, importantly, showed low expression of pro-coagulant phosphatidylserine. LC-MS/MS indicated a rich composition of trophic factors, including neurotrophins, anti-inflammatory agents, neurotransmitters, and antioxidants, unveiling their multifaceted biological functions. PEVs aided in the restoration of neuronal functions in SH-SY5Y cells and demonstrated remarkable neuroprotective capabilities against erastin-induced ferroptosis in dopaminergic neurons. In microglial cells, they promoted anti-inflammatory responses, particularly under inflammatory conditions. In vivo, intranasally delivered PEVs showed strong anti-inflammatory effects in a TBI mouse model and conserved tyrosine hydroxylase expression of dopaminergic neurons of the substantia nigra in a PD model, leading to improved motor function.</p><p><strong>Conclusions: </strong>The potential of PEV-based therapies in neuroprotection opens new therapeutic avenues for neurodegenerative disorders. The study advocates for clinical trials to establish the efficacy of PEV-based biotherapies in neuroregenerative medicine.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"87"},"PeriodicalIF":9.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140253","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}

{"title":"Tudor-SN exacerbates pathological vascular remodeling by promoting the polyubiquitination of PTEN via NEDD4-1.","authors":"Yichen Wu, Zilong Chen, Zhe Zheng, Xiaoguang Li, Jiangcheng Shu, Ruiqi Mao, Jie An, Siyuan Fan, Ruijie Luo, Yi Guo, Wenjing Xu, Minglu Liang, Kai Huang, Cheng Wang","doi":"10.1186/s12929-024-01076-9","DOIUrl":"10.1186/s12929-024-01076-9","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of vascular homeostasis can induce cardiovascular diseases and increase global mortality rates. Although lineage tracing studies have confirmed the pivotal role of modulated vascular smooth muscle cells (VSMCs) in the progression of pathological vascular remodeling, the underlying mechanisms are still unclear.</p><p><strong>Methods: </strong>The expression of Tudor-SN was determined in VSMCs of artery stenosis, PDGF-BB-treated VSMCs and atherosclerotic plaque. Loss- and gain-of-function approaches were used to explore the role of Tudor-SN in the modulation of VSMCs phenotype both in vivo and in vitro.</p><p><strong>Results: </strong>In this study, we demonstrate that Tudor-SN expression is significantly elevated in injury-induced arteries, atherosclerotic plaques, and PDGF-BB-stimulated VSMCs. Tudor-SN deficiency attenuates, but overexpression aggravates the synthetic phenotypic switching of VSMCs and pathological vascular remodeling. Loss of Tudor-SN also reduces atherosclerotic plaque formation and increases plaque stability. Mechanistically, PTEN, the major regulator of the MAPK and PI3K-AKT signaling pathways, plays a vital role in Tudor-SN-mediated regulation on proliferation and migration of VSMCs. Tudor-SN facilitates the polyubiquitination and degradation of PTEN via NEDD4-1, thus exacerbating vascular remodeling under pathological conditions. BpV (HOpic), a specific inhibitor of PTEN, not only counteracts the protective effect of Tudor-SN deficiency on proliferation and migration of VSMCs, but also abrogates the negative effect of carotid artery injury-induced vascular remodeling in mice.</p><p><strong>Conclusions: </strong>Our findings reveal that Tudor-SN deficiency significantly ameliorated pathological vascular remodeling by reducing NEDD4-1-dependent PTEN polyubiquitination, suggesting that Tudor-SN may be a novel target for preventing vascular diseases.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"88"},"PeriodicalIF":9.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140254","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}

{"title":"Dengue NS1 interaction with lipids alters its pathogenic effects on monocyte derived macrophages.","authors":"Shashika Dayarathna, Bhagya Senadheera, Chandima Jeewandara, Madushika Dissanayake, Farha Bary, Graham S Ogg, Gathsaurie Neelika Malavige","doi":"10.1186/s12929-024-01077-8","DOIUrl":"10.1186/s12929-024-01077-8","url":null,"abstract":"<p><strong>Background: </strong>While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there has been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity.</p><p><strong>Methods: </strong>Primary human monocyte derived macrophages (MDMs) were co-cultured with NS1 alone or with HDL, LDL, LPS and/or platelet activating factor (PAF) from individuals with a history of past dengue fever (DF = 8) or dengue haemorrhagic fever (DHF = 8). IL-1β levels were measured in culture supernatants, and gene expression analysis carried out in MDMs. Monocyte subpopulations were assessed by flow cytometry. Hierarchical cluster analysis with Euclidean distance calculations were used to differentiate clusters. Differentially expressed variables were extracted and a classifier model was developed to differentiate between past DF and DHF.</p><p><strong>Results: </strong>Significantly higher levels of IL-1β were seen in culture supernatants when NS1 was co-cultured with LDL (p = 0.01, median = 45.69 pg/ml), but lower levels when NS1 was co-cultured with HDL (p = 0.05, median = 4.617 pg/ml). MDMs of those with past DHF produced higher levels of IL-1β when NS1 was co-cultured with PAF (p = 0.02). MDMs of individuals with past DHF, were significantly more likely to down-regulate RPLP2 gene expression when macrophages were co-cultured with either PAF alone, or NS1 combined with PAF, or NS1 combined with LDL. When NS1 was co-cultured with PAF, HDL or LDL two clusters were detected based on IL10 expression, but these did not differentiate those with past DF or DHF.</p><p><strong>Conclusions: </strong>As RPLP2 is important in DENV replication, regulating cellular stress responses and immune responses and IL-10 is associated with severe disease, it would be important to further explore how differential expression of RPLP2 and IL-10 could lead to disease pathogenesis based on NS1 and lipid interactions.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"86"},"PeriodicalIF":9.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132861","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}