Molecular Biology Reports最新文献

{"title":"Newly designed amplicons-based method for near-full-length genome (NFLG) sequencing of HIV-1 group M recombinant forms.","authors":"Roy Moscona, Tali Wagner, Miranda Geva, Efrat Bucris, Oran Erster, Neta S Zuckerman, Orna Mor","doi":"10.1007/s11033-025-10470-x","DOIUrl":"https://doi.org/10.1007/s11033-025-10470-x","url":null,"abstract":"<p><strong>Background: </strong>Over the years the spread of HIV-1 across the globe resulted in the creation of multiple subtypes and new recombinant forms (RFs). While the pol gene region of the HIV-1 genome is used for resistance mutations analysis and initial detection of RFs, whole genome sequencing analysis is required to determine recombination events across the viral genome. Here, we present a newly designed robust near-full length genome (NFLG) sequencing approach for the sequencing of HIV-1 genomes, out of clinical whole blood samples. This method has been successfully tested for various HIV-1 subtypes and RFs.</p><p><strong>Methods and results: </strong>The method is based on an in-house developed set of 32 pan-genotypic primer pairs, divided into two pools, each containing 16 primer pairs covering the entire HIV-1 genome. Two parallel multiplex PCR reactions were used to generate 32 overlapping DNA fragments spanning the HIV-1 genome. Nextera XT protocol was used to obtain barcoded DNA libraries, which were sequenced with the Illumina Miseq platform using a V3 kit. A consensus sequence was determined for each sample and was used to define recombination events across the genome. For this aim, a combined analysis of several computational tools including HIV BLAST, phylogenetic analysis, RIP, SimPlot +  + and jpHMM were employed. Overall, plasma samples from 33 patients suspected to carry RFs and 2 different, known pure subtypes controls, were included in this study. Genome coverage varied between RFs, while the gag and pol genes were nearly fully covered, the highly variable env gene region was not. Yet, these NFLG analyses enabled the identification of recombination events genome wide.</p><p><strong>Conclusions: </strong>In summary, we describe a methodology for HIV-1 NFLG sequencing, which is based on partially overlapping, multiple PCR fragments, spanning the HIV-1 genome. Additionally, this newly refined method was compared to HIV-1 NFLG results of PCR-free metagenomic sequencing and proved to obtain greater coverage of the HXB2 reference genome. Yet, further testing and validation on a larger cohort is required. Still, this method enables sequencing of 20 different patient samples in a single MiSeq sequencing run and was used for the characterization of different HIV-1 RFs and pure subtypes circulating in Israel.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"362"},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of alcohol-associated liver disease-ferroptosis and autophagy crosstalk.","authors":"Yangyang Wang, Xin Zhou, Hui Chen, Zhi Li","doi":"10.1007/s11033-025-10443-0","DOIUrl":"https://doi.org/10.1007/s11033-025-10443-0","url":null,"abstract":"<p><p>Alcohol-associated liver disease (ALD) is a chronic liver injury caused by prolonged heavy drinking and its pathogenesis is extremely complex. According to current researches, ethanol metabolism and the generation of some of its related metabolites, including acetaldehyde and reactive oxygen species, are significant contributors to hepatocyte toxicity. These substances-induced lipid metabolism disorders, inflammatory response, mitochondrial damage, and cellular oxidative stress are important factors that lead to liver injury. Ethanol has been shown in numerous studies to exacerbate ALD by disrupting autophagy via a variety of mechanisms. ALD can be somewhat alleviated by activating autophagy, which plays a significant role in the development of ALD by removing accumulated protein polymers, damaged mitochondria, and excess lipid droplets from hepatocytes. Furthermore, persistent alcohol use raises serum iron levels, which in turn causes hepatocytes to absorb more iron. This, in turn, encourages iron loading in the liver's and other organs' parenchymal and nonparenchymal cells, finally resulting in ferroptosis. Both ferroptosis and autophagy are significant types of controlled cell death, and new research has revealed that cellular autophagy and a variety of signaling pathways play a key role in the initiation and progression of ferroptosis. Alcohol and iron both have the ability to cause oxidative stress on their own, thus their combined effects hasten liver damage. Iron loading, on the other hand, accelerates the development of ALD by triggering mitochondrial oxidative stress and activating signaling pathways and proteins linked to Ferritinophagy. Thus, we think that a new approach to treating ALD in the future will involve examining the interaction between ferroptosis and mitochondrial autophagy based on iron overload.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"361"},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of plant-derived extracellular vesicles in ameliorating chronic diseases.","authors":"Ashwani Tiwari, Naveen Soni, Shweta Dongre, Megha Chaudhary, Bhawana Bissa","doi":"10.1007/s11033-025-10466-7","DOIUrl":"https://doi.org/10.1007/s11033-025-10466-7","url":null,"abstract":"<p><p>Plant-derived extracellular vesicles (PDEVs) have been shown to have a promising role in treating chronic illnesses. Plants secrete these vesicles containing bioactive chemicals such as proteins, lipids, nucleic acids, and small metabolites. Because of their unique structure, PDEVs affect many biological processes, which makes them an ideal candidate for treating the complex pathophysiology of chronic diseases. Recent studies have shown that PDEVs have anti-inflammatory and antioxidant properties. Extracellular vesicles (EVs) possess diverse therapeutic potential, including anti-inflammatory, antioxidant, and regenerative properties. By regulating immune responses, scavenging free radicals, and promoting tissue repair, EVs can address various chronic diseases such as cardiovascular disorders, neurological conditions, skin diseases, and inflammatory ailments. In preclinical models, PDEVs have been demonstrated to improve heart function and minimize the size of myocardial infarctions. In neurodegenerative illnesses, they can pass through the blood-brain barrier and deliver neuroprotective medicines to the brain. Furthermore, PDEVs have shown promise in enhancing insulin sensitivity and lowering hyperglycemia in diabetic animals. In this review article, we attempt to explain the diverse therapeutic potential of PDEVs in ameliorating chronic diseases.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"360"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of MT2-MMP and MT5-MMP in ulcerative colitis serves a diagnostic predictor and potential therapeutic targets.","authors":"Shohreh Fakhari, Mohammad Moradzad, Amjad Ahmadi, Melika Hekmatnia, Ali Jalili, Bahram Nikkhoo, Mohammad Reza Rahmani, Farshad Sheikhesmaeili","doi":"10.1007/s11033-025-10449-8","DOIUrl":"10.1007/s11033-025-10449-8","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by persistent inflammation and tissue remodeling. Matrix metalloproteinases (MMPs) play a key role in extracellular matrix degradation, and their dysregulation is implicated in IBD. However, the specific role of membrane-type MMPs (MT-MMPs) in UC remains underexplored. This study investigates the expression of MT-MMPs in UC patients, including new cases and treatment-resistant patients, and evaluates their expression patterns compared to healthy people.</p><p><strong>Methods and results: </strong>Colon biopsy samples were collected from three groups: healthy controls (n = 20), newly diagnosed UC patients (n = 20), and UC patients resistant to standard treatments (n = 20). The mRNA expression levels of MT-MMPs were assessed using quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic utility of these MT-MMPs. Correlation analysis was also conducted to explore the relationship between MT-MMPs and inflammatory markers (CRP, ESR) and vitamin D levels. Out of 6 members of MT-MMPs, MT2-MMP, and MT5-MMP were significantly downregulated in new cases and resistant UC patients compared to controls (P < 0.0001). ROC analysis demonstrated high sensitivity and specificity for MT2-MMP and MT5-MMP in differentiating UC patients from healthy individuals. Additionally, MT2,5-MMP expression was negatively correlated with CRP, ESR, and vitamin D levels, indicating their possible modulation of systematic inflammation.</p><p><strong>Conclusion: </strong>MT2-MMP and MT5-MMP are downregulated in UC and may serve as diagnostic biomarkers for disease severity. The findings highlight the need for further investigation into their therapeutic potential in modulating inflammation and tissue remodeling in UC.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"359"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmission dynamics and localization of tomato leaf curl New Delhi virus in cucurbits via sweet potato whitefly, Bemisia tabaci (Gennadius).","authors":"Kathiresan Sivagnanapazham, Gandhi Karthikeyan, Shanmugasundram Pavithran, Sankarasubramanian Harish, Marimuthu Murugan, T K S Latha, Harinarayanan Usha Nandhini Devi","doi":"10.1007/s11033-025-10467-6","DOIUrl":"10.1007/s11033-025-10467-6","url":null,"abstract":"<p><strong>Background: </strong>Bitter gourd (Momordica charantia), ridge gourd (Luffa acutangula), and pumpkin (Cucurbita pepo) are major vegetables of the Cucurbitaceae family cultivated extensively in India. However, their production is severely affected by begomoviruses, which inflict significant global damage to cucurbits. Among these, tomato leaf curl New Delhi virus (ToLCNDV), a whitefly-transmitted, persistent, circulative, and non-propagative begomovirus, seriously threatens cucurbit cultivation, often leading to substantial yield losses.</p><p><strong>Methods and results: </strong>Understanding the interactions between vectors and viruses is therefore critical. This study explored the transmission dynamics, localization, and titre of ToLCNDV in bitter gourd, ridge gourd, and pumpkin. A maximum transmission rate of 80% was achieved when 15 whiteflies (Asia I cryptic species) were given an acquisition access period (AAP) and an inoculation access period (IAP) of 24 h. However, transmission was observed even after 1 h of AAP and IAP respectively. Immunofluorescent assays showed that ToLCNDV accumulated as vesicle-like structures in the midgut and salivary glands of B. tabaci. Using conventional PCR, ToLCNDV yielded an expected amplicon size of 1500 bp in the midgut and salivary gland DNAs of B. tabaci. The maximum viral titre of 7.2 × 10⁷, 3.4 × 10⁶ and 1.3 × 10⁶ copies per µl at 24 h of IAP were observed in 20-day post-inoculation symptomatic leaves of bitter gourd, ridge gourd and pumpkin, respectively.</p><p><strong>Conclusions: </strong>Bemisia tabaci (Asia I) efficiently transmitted ToLCNDV in bitter gourd, ridge gourd, and pumpkin. Localization studies confirmed the presence of virus particles in the midgut and salivary glands of viruliferous whiteflies. qPCR assays quantified viral titres in infected cucurbit crops. These findings enhance the understanding of virus-vector interactions and provide valuable insights for developing effective management strategies to combat leaf curl disease in cucurbits.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"358"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic diversity and antibiogram of ESBL-producing Escherichia coli isolated from apparently healthy birds sold at two selected live bird markets in Nigeria.","authors":"Adetolase A Bakre, Abimbola O Adekanmbi, Ibatullah Ajani, Pelumi Festus","doi":"10.1007/s11033-025-10445-y","DOIUrl":"https://doi.org/10.1007/s11033-025-10445-y","url":null,"abstract":"<p><strong>Background: </strong>Live bird markets (LBMs) play a crucial role in the poultry value chain. However, there is a significant threat of antibiotic resistance development via this chain. This study aimed to characterise ESBL-producing Escherichia coli (E. coli) from cloacal samples of apparently healthy ducks and pigeons, determine their antibiotic resistance profile and carriage of ESBL genes.</p><p><strong>Methods and results: </strong>Sasa and Molete LBMs were selected for this study. Three hundred and forty cloacal swabs (170 each from ducks and pigeons) were sampled and isolation of E. coli was done using the streak plate method. Resistance to a panel of 10 antibiotics was determined using the disc diffusion method and phenotypic ESBL production was carried out using the double disc synergy test (DDST). Detection of ESBL genes in the isolates was done using PCR amplification method. Out of 340 samples, 22.9% (n = 78) tested positive for E. coli. Among these, 38.5% (n = 30) were positive for ESBL production. The thirty ESBL-producing isolates showed varying level of resistance to the tested antibiotics, with the highest level of resistance observed to imipenem in both ducks and pigeons. Twenty of the ESBL producers showed multidrug-resistant phenotypes. bla_CTX-M which was detected in 19 isolates (63.3%) was the most predominant ESBL gene among the isolates, while 15/30 (50.0%) carried bla_SHV and 6/30 (20.0%) carried bla_TEM. Thirteen (43.3%) and two (6.6%) isolates co-harboured two and all the three target ESBL genes, respectively.</p><p><strong>Conclusions: </strong>This study has shown that LBMs in Ibadan are a repository of multidrug-resistant and ESBL-producing E. coli, hence urgent measures need to be taken to monitor and control the use of antibiotics in LBMs to mitigate this risk.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"357"},"PeriodicalIF":2.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-526b enhances glucose metabolism in breast cancer cells, an effect reversed by targeting the COX-2/EP4 pathway.","authors":"Braydon D Nault, Mousumi Majumder","doi":"10.1007/s11033-025-10430-5","DOIUrl":"10.1007/s11033-025-10430-5","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer cells reprogram metabolic pathways to meet energy demands and sustain rapid growth, a hallmark of malignancy. Identifying molecular signatures underlying these changes can aid in early detection and inform targeted therapies. miR-526b has been shown to promote migration, invasion, angiogenesis, and metastasis, yet its role in dysregulated glucose metabolism remains underexplored.</p><p><strong>Methods: </strong>We used MCF7 (Luminal A) and SKBR3 (HER2-Enriched) breast cancer cell lines, which exhibit distinct metabolic characteristics, to study miR-526b's impact on metabolic marker expression, ATP production, oxygen consumption rate, and extracellular acidification. Cells were treated with glycolysis inhibitor 2 Deoxy-D-Glucose (2DG) or ox-phos inhibitor Oligomycin (OM) to measure dependence on glycolysis or oxidative phosphorylation. Stable transfection was used to overexpress miR-526b in MCF7 and SKBR3 cell lines, and miRNA inhibitors were used to inhibit miR-526b in MCF7-COX2 cells, comparing its effects across subtypes. Targeted inhibition of EP4 with a specific antagonist (EP4A) RQ-15986 (CJ-042794) was done in aggressive MCF7-COX2 cells to test the involvement of COX-2/EP4.</p><p><strong>Results: </strong>SKBR3 exhibits an enhanced glycolytic phenotype, while MCF7 demonstrates increased ox-phos metabolism. Overexpression of miR-526b amplified these inherent metabolic properties, increasing ATP production and proliferation in both cell lines. miR-526b enhanced ox-phos activity in MCF7, reducing sensitivity to glycolysis inhibition, whereas it amplified glycolytic metabolism in SKBR3, reducing sensitivity to ox-phos inhibition. Overexpression of COX-2 in MCF7 replicated the metabolic effects of miR-526b. Inhibition of miR-526b in MCF7-COX2 cells enhances HK2 and GLUT1 expression, but did not significantly alter cell proliferation or cell viability. Targeting the COX-2/EP4 axis with a selective EP4A reversed the transcriptomic changes induced by miR-526b, but did not reduce the increased proliferation observed in MCF7-COX2.</p><p><strong>Conclusion: </strong>miR-526b enhances inherent metabolic characteristics of breast cancer cell lines, increasing ATP production, proliferation, and resistance to metabolic inhibitors. Targeting the COX-2/EP4 axis mitigated some of the effects induced by miR-526b, but it did not normalize cell behavior, highlights the complex regulation of glucose metabolism in breast cancer and underscores the need for combination therapy strategies.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"351"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective mechanisms of microglia in ischemic stroke: a review focused on mitochondria.","authors":"Jiale Gan, Xinyi Yang, Jianan Wu, Peian Liu, Zhaoyao Chen, Yue Hu, Wenlei Li, Yuan Zhu, Minghua Wu","doi":"10.1007/s11033-025-10469-4","DOIUrl":"https://doi.org/10.1007/s11033-025-10469-4","url":null,"abstract":"<p><p>Stroke encompasses a range of cerebrovascular disorders characterized by high morbidity, disability, and mortality, with ischemic stroke being the predominant type. This condition imposes significant socio-economic and healthcare burdens, and therapeutic options are currently limited. Microglia, the brain's resident immune cells, are rapidly activated following stroke-induced injury and play a pivotal role in the pathogenesis of neuroinflammation and ischemic tissues. Mitochondria participates in and influences the pathological processes of ischemic stroke, including oxidative stress, modulation of microglia phenotype, and axonal regenerative function, and is an essential and often overlooked target in the clinical management of stroke. This paper reviews recent advancements in research on microglia in ischemic stroke, specifically focusing on the contribution of the mitochondria, providing a reference for selecting therapeutic targets and guiding future research directions.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"355"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aquaporin 3 inhibition attenuates imiquimod-induced psoriatic symptoms in a murine model.","authors":"Ryosuke Okubo, Manami Tanaka, Akiharu Kubo, Masato Yasui, Mariko Hara-Chikuma","doi":"10.1007/s11033-025-10444-z","DOIUrl":"https://doi.org/10.1007/s11033-025-10444-z","url":null,"abstract":"<p><strong>Background: </strong>Aquaporin 3 (AQP3) is highly expressed in both keratinocytes and T cells within psoriatic skin. Previous studies have demonstrated that AQP3 knockout mice show reduced development of psoriatic symptoms in murine models. This study aims to evaluate the effect of AQP3 inhibition on psoriasis progression.</p><p><strong>Methods and results: </strong>AQP3 conditional knockout mice were generated to assess the role of AQP3 expression in keratinocytes and T cells in psoriasis pathogenesis. In an imiquimod (IMQ)-induced psoriasis model, psoriatic symptoms were significantly reduced in mice with keratinocyte-specific AQP3 deletion. Additionally, AQP3 inhibition by administration of anti-AQP3 monoclonal antibody (mAb) effectively alleviated IMQ-induced psoriasis symptoms in wild-type mice.</p><p><strong>Conclusions: </strong>AQP3 inhibition presents a promising approach for the treatment of psoriasis.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"354"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing exosome-mediated angiotensin-converting enzyme 2 expression modulation: activation of human Wharton's jelly mesenchymal stem cells derived exosomes through curcumin and quinine.","authors":"Marselina Irasonia Tan, Nayla Majeda Alfarafisa, Alfina Gracia Feronytha, Arif Ibrahim Ardisasmita, Anggraini Barlian, Popi Septiani","doi":"10.1007/s11033-025-10454-x","DOIUrl":"https://doi.org/10.1007/s11033-025-10454-x","url":null,"abstract":"<p><strong>Background: </strong>Cell-free therapy utilizes components such as secretomes and exosomes whose properties depend on the cellular environment. This study investigates how altering the microenvironment of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) with curcumin and quinine affects exosome content, potentially influencing ACE2 expression in Vero and Caco-2 cells.</p><p><strong>Methods and results: </strong>hWJ-MSCs were divided into groups treated with curcumin, quinine, DMSO or culture medium only. Secretomes and exosomes were isolated and analyzed, with exosomes characterized by CD63 marker, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Exosome uptake by Vero and Caco-2 cells was monitored over time, and ACE2 expression was assessed by immunocytochemistry (ICC) and Western blotting. The results of this study demonstrated that exosomes averaged 114.3 nm in size and contained 88 miRNAs, with significant miRNA reductions in exosomes treated with curcumin and quinine. Vero and Caco-2 cells internalized these exosomes within 2.5 h and showed a significant decrease in ACE2 expression when treated with curcumin- or quinine-treated exosomes. This effect was associated with changes in miRNA, including miR-125b-5p in treated exosomes. Exosomes modified with curcumin or quinine significantly downregulated ACE2 expression, suggesting that these compounds may affect miRNA expression or loading, thereby affecting ACE2 protein expression.</p><p><strong>Conclusion: </strong>This study highlights the therapeutic potential of bioactive compounds in modulating ACE2 through exosome-carried biomolecules. These findings suggest a potential therapeutic strategy for condition associated with ACE2 dysregulation and warrant further investigation into molecular mechanism involved.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"352"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}