Danila Zimenkov, Vyacheslav Zhuravlev, Anastasia Ushtanit, Marina Filippova, Uliana Semenova, Natalia Solovieva, Maria Sviridenko, Anastasia Khakhalina, Svetlana Safonova, Marina Makarova, Elizaveta Gordeeva, Elena Guselnikova, Yakov Schwartz, Natalia Stavitskaya, Peter Yablonsky
{"title":"Biochip-Based Identification of Mycobacterial Species in Russia.","authors":"Danila Zimenkov, Vyacheslav Zhuravlev, Anastasia Ushtanit, Marina Filippova, Uliana Semenova, Natalia Solovieva, Maria Sviridenko, Anastasia Khakhalina, Svetlana Safonova, Marina Makarova, Elizaveta Gordeeva, Elena Guselnikova, Yakov Schwartz, Natalia Stavitskaya, Peter Yablonsky","doi":"10.3390/ijms252313200","DOIUrl":"https://doi.org/10.3390/ijms252313200","url":null,"abstract":"<p><p>Infections caused by nontuberculous mycobacteria (NTM) are rising globally throughout the world. The number of species isolated from clinical samples is steadily growing, which demands the implementation of a robust diagnostic method with wide specificity. This study was carried out in in 2022-2024 in three clinical antituberculosis centers in the biggest cities of Russia: Moscow, Saint Petersburg, and Novosibirsk. We developed the DNA hybridization assay 'Myco-biochip' that allows the identification of 79 mycobacterial species and analyzed 3119 samples from 2221 patients. Sixty-eight mycobacterial species were identified in clinics, including the three novel species phylogenetically related to <i>M. duvalii</i>, <i>M. lentiflavum</i>, and <i>M. talmoniae</i>. The identification of a close relative of <i>M. talmoniae</i> adds to the existence of separate clade between <i>M. terrae</i>, <i>M. triviale</i> complexes and other slow-growing <i>Mycobacteria</i>, which supports the thesis against the splitting of <i>Mycobacteria</i> into five separate genera. Adding to the list of potentially pathogenic species, we identified <i>M. adipatum</i> and <i>M. terramassiliense</i>, which were previously described as natural habitats. The diversity of acid-fast bacilli identified in TB-suspected persons was not limited to the <i>Mycobacteria</i> genus and also includes species from genera <i>Nocardia</i>, <i>Gordonia</i>, <i>Corynebacterium</i>, <i>Tsukamurella</i>, and <i>Rhodococcus</i> of the order <i>Mycobacteriales</i>. The revealed bacterial diversity in patients with suspected NTM-diseases requires the implementation of relevant species identification assays as the first step in the laboratory diagnostic pipeline.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pichchapa Linsaenkart, Wipawadee Yooin, Supat Jiranusornkul, Korawan Sringarm, Chaiwat Arjin, Pornchai Rachtanapun, Kittisak Jantanasakulwong, Juan M Castagnini, Warintorn Ruksiriwanich
{"title":"Valorization of Hom Thong Banana Peel (<i>Musa</i> sp., AAA Group) as an Anti-Melanogenic Agent Through Inhibition of Pigmentary Genes and Molecular Docking Study.","authors":"Pichchapa Linsaenkart, Wipawadee Yooin, Supat Jiranusornkul, Korawan Sringarm, Chaiwat Arjin, Pornchai Rachtanapun, Kittisak Jantanasakulwong, Juan M Castagnini, Warintorn Ruksiriwanich","doi":"10.3390/ijms252313202","DOIUrl":"https://doi.org/10.3390/ijms252313202","url":null,"abstract":"<p><p>Prolonged and unprotected exposure to the environment explicitly influences the development of hyperpigmented lesions. The enzyme tyrosinase (TYR) is a key target for regulating melanin synthesis. Several bioactive compounds derived from plant extracts have been found to possess potent anti-melanogenesis properties against TYR. In particular, the potential of banana peels from various varieties has garnered interest due to their application in skin hyperpigmentation treatment. A molecular docking study demonstrated interactions between rosmarinic acid, which is predominantly found in all Hom Thong peel extracts, and the active site of TYR (PDB ID: 2Y9X) at residues HIS263, VAL283, SER282, and MET280, with the lowest binding energy of -5.05 kcal/mol, showing the strongest interaction. Additionally, Hom Thong banana peels are rich in phenolic compounds that could inhibit melanin content and tyrosinase activity in both human and mouse melanoma cells. These effects may be attributed to the suppression of gene expression related to melanogenesis, including the regulator gene <i>MITF</i> and pigmentary genes <i>TYR</i>, <i>TRP-1</i>, and <i>DCT</i>, indicating effects comparable to those of the standard treatment groups with arbutin and kojic acid. Our findings indicated the potential of Hom Thong peel extracts as anti-melanogenic agents.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dopamine: A New Player in the Pathogenesis of Diabetic Retinopathy?","authors":"Marianthi Ntikoudi, Theofano Myrto Farmaki, Konstantinos Tziomalos","doi":"10.3390/ijms252313196","DOIUrl":"https://doi.org/10.3390/ijms252313196","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is a leading cause of blindness. The pathogenesis of diabetic retinopathy is multifactorial and incompletely understood. Accordingly, treatment options are limited. Recent data suggest that dopamine might play a role in the development and progression of DR. In the present review, we discuss these data and comment on the potential role of dopamine modulation in the management of this devastating microvascular complication of diabetes mellitus.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Ágnes Molnár, Kristóf Birgés, Adrienn Surman, Béla Merkely
{"title":"The Complex Connection Between Myocardial Dysfunction and Cancer Beyond Cardiotoxicity: Shared Risk Factors and Common Molecular Pathways.","authors":"Andrea Ágnes Molnár, Kristóf Birgés, Adrienn Surman, Béla Merkely","doi":"10.3390/ijms252313185","DOIUrl":"https://doi.org/10.3390/ijms252313185","url":null,"abstract":"<p><p>Cardiovascular diseases and cancer represent the largest disease burden worldwide. Previously, these two conditions were considered independent, except in terms of cardiotoxicity, which links cancer treatment to subsequent cardiovascular issues. However, recent studies suggest that there are further connections between cancer and heart disease beyond cardiotoxicity. It has been revealed that myocardial dysfunction may promote carcinogenesis, indicating that additional common pathophysiological mechanisms might be involved in the relationship between cardiology and oncology, rather than simply a connection through cardiotoxic effects. These mechanisms may include shared risk factors and common molecular pathways, such as persistent inflammation and neurohormonal activation. This review explores the connection between myocardial dysfunction and cancer, emphasizing their shared risk factors, similar biological mechanisms, and causative factors like cardiotoxicity, along with their clinical implications.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Souvik Patra, Chantal J McMillan, Elisabeth R Snead, Amy L Warren, Kevin Cosford, Prasanth K Chelikani
{"title":"Feline Diabetes Is Associated with Deficits in Markers of Insulin Signaling in Peripheral Tissues.","authors":"Souvik Patra, Chantal J McMillan, Elisabeth R Snead, Amy L Warren, Kevin Cosford, Prasanth K Chelikani","doi":"10.3390/ijms252313195","DOIUrl":"https://doi.org/10.3390/ijms252313195","url":null,"abstract":"<p><p>Like humans, cats have a strong relationship between decreasing insulin sensitivity and the development of diabetes with obesity. However, the underlying molecular mechanisms of impaired insulin secretion and signaling in cats remain largely unknown. A total of 54 client-owned nondiabetic lean (<i>n</i> = 15), overweight (<i>n</i> = 15), and diabetic (<i>n</i> = 24) cats were included in the study. The pancreas, liver, and skeletal muscle were quantified for mRNA and protein abundances of insulin and incretin signaling markers. Diabetic cats showed increased liver and muscle adiposity. The pancreas of diabetic cats had decreased transcript abundances of insulin, insulin receptor, insulin-receptor substrate (IRS)-1, glucose transporters (GLUT), and protein abundance of mitogen-activated protein kinase. In treated diabetics, protein abundance of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide receptors, total and phosphorylated Akt, and GLUT-1 were increased in the pancreas, whereas untreated diabetics had downregulation of markers of insulin and incretin signaling. In the muscle and liver, diabetic cats had reduced mRNA abundances of insulin receptor, IRS-1/2, and phosphatidylinositol-3-kinase, and reduced protein abundances of GLUT-4 and phosphatidylinositol-3-kinase-p85α in muscle. We demonstrate that feline diabetes is associated with ectopic lipid deposition in the liver and skeletal muscle, deficits in insulin synthesis and incretin signaling in the pancreas, and impaired insulin signaling in the muscle and liver. These findings have implications for understanding the pathophysiological mechanisms of obesity and diabetes in humans and pets.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hewei Jiang, Jin Xie, Lei Wang, Hong Chen, Yunxiao Zheng, Xuening Wang, Shujuan Guo, Tao Wang, Jing Bi, Xuelian Zhang, Jianfeng Pei, Shengce Tao
{"title":"Structure-Based Screening and Optimization of PafA Inhibitors with Potent Anti-Tuberculosis Activity.","authors":"Hewei Jiang, Jin Xie, Lei Wang, Hong Chen, Yunxiao Zheng, Xuening Wang, Shujuan Guo, Tao Wang, Jing Bi, Xuelian Zhang, Jianfeng Pei, Shengce Tao","doi":"10.3390/ijms252313189","DOIUrl":"https://doi.org/10.3390/ijms252313189","url":null,"abstract":"<p><p>Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), remains a major global health challenge, primarily due to the increasing prevalence of drug resistance. Consequently, the development of drugs with novel modes of action (MOAs) is urgently required. In this study, we discovered and characterized two potent inhibitors, Pi-1-58 and Pi-2-26, targeting the prokaryotic ubiquitin-like protein (Pup) ligase PafA of <i>Mtb</i>. Pi-1-58 was identified through computer-aided drug screening. The binding mode of Pi-1-58 and PafA was investigated through molecular docking, followed by experimental validations. Based on the core structure of Pi-1-58, we developed a more potent inhibitor, Pi-2-26, through structure-guided drug design. Both Pi-1-58 and Pi-2-26 exhibited selective and specific inhibition of PafA according to biochemical and cell-based assays. Importantly, the inhibitors demonstrated significant inhibition on <i>Mtb</i> survival in the presence of nitric oxide, mimicking the in vivo nitrogen limited environment that <i>Mtb</i> encountered in macrophage. Our findings provide a comprehensive understanding of the structural and functional aspects of these PafA inhibitors and establish a solid foundation for the development of novel therapeutics against tuberculosis.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling the Role of β-Glucosidase Genes in <i>Bletilla striata</i>'s Secondary Metabolism: A Genome-Wide Analysis.","authors":"Mengwei Xu, Hongwei Li, Hongyuan Luo, Jingyi Liu, Kunqian Li, Qingqing Li, Ning Yang, Delin Xu","doi":"10.3390/ijms252313191","DOIUrl":"https://doi.org/10.3390/ijms252313191","url":null,"abstract":"<p><p>β-glucosidases (BGLUs) are abundant enzymes in plants that play pivotal roles in cell wall modification, hormone signal transduction, secondary metabolism, defense against herbivores, and volatile compound release. <i>Bletilla striata</i>, a perennial herb revered for its therapeutic properties, lacks a comprehensive analysis of its <i>BGLU</i> gene family despite the critical role these genes play in plant secondary metabolism. This study aims to perform a genome-wide analysis of the <i>BGLU</i> gene family in <i>B. striata</i> (<i>BsBGLU</i>) to elucidate their functions and regulatory mechanisms in secondary metabolite biosynthesis. We conducted a genome-wide screening to identify <i>BsBGLU</i>, followed by phylogenetic analysis to classify these genes into groups. Sequence characteristics were analyzed to predict functional roles. Simple sequence repeat (SSR) markers were examined to assess conservation and polymorphism among different landraces. Expression profiles of <i>BsBGLUs</i> were evaluated under sodium acetate and salicylic acid elicitor treatments and across different tissues. The accumulation of phylogenetic metabolites in different treatments and tissues was also analyzed by HPLC and LCMS detection to explore the correlation between gene expression and metabolite accumulation. A total of 23 <i>BsBGLU</i> genes were identified and classified into eight distinct groups. Sequence analysis suggested diverse functions related to hormone responses, secondary metabolism, and stress resistance. <i>BsBGLUs</i> with SSR sequences were conserved yet showed polymorphism among different <i>B. striata</i> landraces. Under elicitor treatments, expression profiling revealed that <i>BsBGLUs</i> significantly modulate the synthesis of secondary metabolites such as dactylorhin A and militarine. Tissue-specific expression analysis indicated that <i>BsBGLU15</i> and <i>BsBGLU28</i> were highly expressed in tubers compared to other tissues, suggesting their central role and a potential negative regulatory effect in metabolite accumulation. The elicitor NaAc can regulate metabolite synthesis by modulating the expression of <i>BsBGLUs</i>. The <i>BsBGLU</i> gene family in <i>B. striata</i> is integral to the modulation of secondary metabolite biosynthesis and accumulation and can respond to elicitors to promote the synthesis of militarine. These findings provide a theoretical foundation for the further exploration of <i>BsBGLU</i> gene functions and their regulatory mechanisms, advancing the production of medicinally active compounds in <i>B. striata.</i></p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Wheat WW Domain-Containing Protein TaCFL1 Negatively Regulates Cuticular Wax Biosynthesis.","authors":"Wanzhen Chen, Lang Liu, Xiaoyu Wang, Haoyu Li, Jiao Liu, Pengfei Zhi, Cheng Chang","doi":"10.3390/ijms252313187","DOIUrl":"https://doi.org/10.3390/ijms252313187","url":null,"abstract":"<p><p>Waxy cuticle covers plant aerial organs and protects plants against environmental challenges. Although improved cuticle-associated traits are aimed at the wheat breeding programs, the mechanism governing wheat cuticular wax biosynthesis remains to be elucidated. Herein, wheat WW domain-containing protein TaCFL1 is characterized as a negative regulator of wax biosynthesis. The knockdown of <i>TaCFL1</i> expression results in a 15% increase in wax accumulation and decreased leaf cuticle permeability in bread wheat. Furthermore, wheat class IV homeodomain transcription factors TaHDG1.1 and TaHDG1.2 are identified as partially redundant activators of wax biosynthesis. The silencing of <i>TaHDG1.1</i> or <i>TaHDG1.2</i> expression leads to an 11% reduction in epidermal wax accumulation and an increase in leaf cuticle permeability wax, while the co-silencing of <i>TaHDG1.1</i> and <i>TaHDG1.2</i> results in a 31% reduction in epidermal wax accumulation and a further increase in wax in the leaf cuticle permeability. Moreover, wheat 3-Ketoacyl-CoA synthase TaKCS10 is isolated as an essential component of the wax biosynthetic machinery. The silencing of <i>TaKCS10</i> expression results in a 22% reduction in wax accumulation and increased leaf cuticle permeability. In addition, we demonstrated that the <i>TaKCS10</i> expression is activated by TaHDG1.1 and TaHDG1.2, and that TaCFL1 attenuates the TaHDG1-mediated transcriptional activation of <i>TaKCS10</i>. This evidence supports that the WW domain-containing protein TaCFL1 negatively regulates wax biosynthesis via attenuating the transcriptional activation of the <i>TaKCS10</i> gene mediated by HD-ZIP IV transcription factor TaHDG1.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia Wrońska, Aleksandra Felczak, Katarzyna Niedziałkowska, Marta Kędzierska, Maria Bryszewska, Mohamed Amine Benzaouia, Abdelkrim El Kadib, Katarzyna Miłowska, Katarzyna Lisowska
{"title":"Antifungal Chitosan Nanocomposites-A New Perspective for Extending Food Storage.","authors":"Natalia Wrońska, Aleksandra Felczak, Katarzyna Niedziałkowska, Marta Kędzierska, Maria Bryszewska, Mohamed Amine Benzaouia, Abdelkrim El Kadib, Katarzyna Miłowska, Katarzyna Lisowska","doi":"10.3390/ijms252313186","DOIUrl":"https://doi.org/10.3390/ijms252313186","url":null,"abstract":"<p><p>Chitosan, a biopolymer derived from chitin, exhibits significant antifungal properties, making it a valuable compound for various applications in agriculture food preservation, and biomedicine. The present study aimed to assess the antifungal properties of chitosan-modified films using sol-gel derivatives (CS:ZnO) or graphene-filled chitosan, (CS:GO and CS:rGO) against two strains of fungi that are the most common cause of food spoilage: <i>Aspergillus flavus</i> ATCC 9643 and <i>Penicillium expansum</i> DSM 1282. The results indicate important differences in the antifungal activity of native chitosan films and zinc oxide-modified chitosan films. CS:ZnO nanocomposites (2:1 and 5:1) completely inhibited spore germination of the two tested fungal strains. Furthermore, a decrease in spore viability was observed after exposure to CS:Zn films. Significant differences in the permeability of cell envelopes were observed in the <i>A. flavus</i>. Moreover, the genotoxicity of the materials against two cell lines, human BJ fibroblasts and human KERTr keratinocytes, was investigated. Our studies showed that the tested nanocomposites did not exhibit genotoxicity towards human skin fibroblasts, and significant damage in the DNA of keratinocytes treated with CS:ZnO composites. Nanocomposites based on chitosan may help reduce synthetic fungicides and contribute to sustainable food production and food preservation practices.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nader Kameli, Heike E F Becker, Daisy M Jonkers, John Penders, Paul Savelkoul, Frank Stassen
{"title":"Investigating the Immunomodulatory Impact of Fecal Bacterial Membrane Vesicles and Their IgA Coating Patterns in Crohn's Disease Patients.","authors":"Nader Kameli, Heike E F Becker, Daisy M Jonkers, John Penders, Paul Savelkoul, Frank Stassen","doi":"10.3390/ijms252313194","DOIUrl":"https://doi.org/10.3390/ijms252313194","url":null,"abstract":"<p><p>The human intestinal tract contains trillions of bacteria that coexist in a symbiotic relationship with human cells. Imbalances in this interaction can lead to disorders such as Crohn's disease (CD). Bacteria membrane vesicles (MVs), which are released by almost all bacteria, have been demonstrated to play a crucial role in bacteria-host interactions. In this study, we assessed the physical characterizations, immunomodulatory effects, and IgA interactions of MVs derived from fecal samples of CD patients and healthy controls (HCs). MVs were isolated from the frozen fecal samples using a combination of ultrafiltration and size-exclusion chromatography. Using nanoparticle tracking analysis, we found that the MVs of the CD patients showed a significantly lower concentration compared to those of the HCs. Cryo-transmission electron microscopy revealed the larger size of the MVs in active CD (Ac-CD) compared to the MVs of remission CD (Re-CD) and HCs. Differentiated monocyte THP-1 cells released more TNF-a when exposed to MVs from the HCs compared to the CD patients. On the other hand, the MVs from the HCs and Re-CD patients but not the Ac-CD patients induced more anti-inflammatory IL-10. Intriguingly, bead-based flow cytometry analysis showed that the MVs of the HCs and Re-CD patients were more coated with IgA compared to those of the Ac-CD patients. These results suggest the potential role of MVs in the immunomodulatory impact on the pathophysiology of CD. Moreover, IgA seems to regulate these effects by direct binding, which was not the case for the Ac-CD patients. Finally, the IgA coating patterns of the MVs could be used as an additional disease biomarker, as they can clearly identify the exacerbation status of CD.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}