vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-26-84vavilov-5237Research ArticleБИОИНФОРМАТИКА И СИСТЕМНАЯ БИОЛОГИЯBIOINFORMATICS AND SYSTEMS BIOLOGYВыявление потенциальных генов-мишеней малых некодирующих фрагментов тРНК трематод среди дифференциально экспрессирующихся генов моноцитов человекаIdentification of potential target genes of the trematode transport RNA-derived small RNAs among differentially expressed genes of human monocytesЛишайЕ. А.LishaiE. A.

Новосибирск

Novosibirsk

lishai.ekaterina@gmail.comПахаруковаМ. Ю.PakharukovaM. Y.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian Federation202626082026305830838Copyright © Лишай Е.А., Пахарукова М.Ю., 20262026Лишай Е.А., Пахарукова М.Ю.Lishai E.A., Pakharukova M.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/5237

РНК-интерференция – эволюционно консервативный механизм посттранскрипционной регуляции генов, представленный у всех видов живых организмов, в настоящее время актуален для многих направлений молекулярной медицины, включая диагностику и новые подходы к иммуномодуляции. В последнее время появляется все больше данных об участии внеклеточных везикул и их компонентов в контексте взаимодействия между паразитом и хозяином. Трематода Opisthorchis felineus, паразитирующая в желчных протоках человека, вызывает описторхоз, что сопровождается хроническим воспалением и рядом неблагоприятных последствий.

Длительное выживание паразита, вероятно, связано с иммуномодуляцией хозяина. Однако механизм влияния везикул трематод на моноциты человека неизвестен. Целью настоящей работы было найти потенциальные гены-мишени фрагментов тРНК трематод в геноме человека и проанализировать их представленность среди дифференциально экспрессирующихся генов (ДЭГ) в транскриптоме моноцитов человека линии THP-1. В результате поиска генов-мишеней для восьми наиболее представленных фрагментов тРНК O. felineus было выявлено 1299 потенциальных генов, которые могут быть мишенями в моноцитах человека. Семь кДНК библиотек клеточной культуры моноцитов человека линии THP-1 до и после обработки выделенными везикулами взрослой особи O. felineus были просеквенированы методом парных прочтений 2 × 150 пар оснований (технология DNBseq, BGI, Китай), получено около 43.8 млн прочтений на библиотеку. Среди 1484 ДЭГ в моноцитах было обнаружено 159 генов-мишеней фрагментов тРНК везикул, экспрессия которых значимо менялась при обработке экзосомоподобных везикул (ЭПВ). Выявленные потенциальные гены-мишени относились к путям, связанным с регуляцией клеточного цикла и клеточной гибели (контроль целостности ДНК (M16357), переход из фазы G1 в фазу S (M2074), апоптоз (M15303) и программируемая клеточная гибель (M27436)), иммунного ответа (путь моноцитов (M4956), дифференцировка мононуклеарных макрофагов (M25144), презентация антигена через MHC-1 (M1066), процессинг антигена через протеасому (M1070)). Вероятно, фрагменты тРНК трематоды O. felineus могут вносить вклад в регуляцию этих процессов в моноцитах хозяина.

RNA interference is an evolutionarily conserved mechanism of post-transcriptional gene expression regulation present in all living organisms. It is highly relevant to multiple areas of molecular medicine, including diagnostics and novel immunomodulatory approaches. Recent studies have increasingly highlighted the role of extracellular vesicles and their cargo in parasite-host interactions. The trematode Opisthorchis felineus, which parasitizes the human biliary tract, causes opisthorchiasis, a disease associated with chronic inflammation and other hepatobiliary injuries. The long-term survival of the parasite is likely linked to modulation of host immune response. Nevertheless, the mechanism by which liver fluke vesicles affect human immune cells remains unclear. The aim of this study was to identify potential human gene targets of tRNA-derived small RNAs and to assess their enrichment among differentially expressed genes (DEGs) in the transcriptome of THP-1 human monocytes. Target prediction for eight most abundant O. felineus tRNA fragments identified 1,299 potential target genes in human monocytes. Seven cDNA libraries prepared from THP-1 monocytes  before and after treatment with vesicles from adult O. felineus were sequenced using paired-end 2 × 150 bp sequencing (DNBseq, BGI), yielding 43.8 million reads per library. Among 1484 DEGs, 159 predicted targets of tRNA-derived small RNAs showed significant expression changes upon vesicle treatment. These genes were associated with pathways involved in cell-cycle regulation and cell death, including DNA integrity control (M16357), G1/S transition (M2074), apoptosis (M15303), and programmed cell death (M27436), as well as immune-related pathways, including the monocyte pathway (M4956), mononuclear macrophage differentiation (M25144), MHC-I antigen presentation (M1066), and proteasomemediated antigen processing (M1070). These findings suggests that O. felineus tRNA-derived small RNAs may contribute to the regulation of these processes in human monocytes.

описторхозтРНКэкзосомо-подобные везикулыРНК-интерференциятранскриптомикамоно- циты человекаopisthorchiasistRNAexosome-like vesiclesRNA interferencetranscriptomicshuman monocytesThis work was supported by the Russian Science Foundation (grant No. 24-44-00048). Acknowledgements. Bioinformatic analyses were performed using the computational resources of the Bioinformatics Core Facility at the Institute of Cytology and Genetics SB RAS (project FWNR-2026-0027).ReferencesAraújo M.I., Hoppe B.S., Medeiros M. Jr, Carvalho E.M. Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases. Mem Inst Oswaldo Cruz. 2004;99(5): 27-32. doi 10.1590/s0074-02762004000900005Araújo M.I., Hoppe B.S., Medeiros M. Jr, Carvalho E.M. Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases. Mem Inst Oswaldo Cruz. 2004;99(5): 27-32. doi 10.1590/s0074-02762004000900005Artuyants A., Campos T.L., Rai A.K., Johnson P.J., Dauros-Singorenko P., Phillips A., Simoes-Barbosa A. Extracellular vesicles produced by the protozoan parasite Trichomonas vaginalis contain a preferential cargo of tRNA-derived small RNAs. Int J Parasitol. 2020; 50(14):1145-1155. doi 10.1016/j.ijpara.2020.07.003Artuyants A., Campos T.L., Rai A.K., Johnson P.J., Dauros-Singorenko P., Phillips A., Simoes-Barbosa A. Extracellular vesicles produced by the protozoan parasite Trichomonas vaginalis contain a preferential cargo of tRNA-derived small RNAs. Int J Parasitol. 2020; 50(14):1145-1155. doi 10.1016/j.ijpara.2020.07.003Bhuva D., Smyth G., Garnham A. msigdb: an ExperimentHub package for the Molecular Signatures Database (MSigDB). R package version 1.18.0. 2025. doi 10.18129/B9.bioc.msigdbBhuva D., Smyth G., Garnham A. msigdb: an ExperimentHub package for the Molecular Signatures Database (MSigDB). R package version 1.18.0. 2025. doi 10.18129/B9.bioc.msigdbBosshart H., Heinzelmann M. THP-1 cells as a model for human monocytes. Ann Transl Med. 2016;4(21):438. doi 10.21037/atm.2016. 08.53Bosshart H., Heinzelmann M. THP-1 cells as a model for human monocytes. Ann Transl Med. 2016;4(21):438. doi 10.21037/atm.2016. 08.53Chan P.P., Lin B.Y., Mak A.J., Lowe T.M. tRNAscan-SE 2.0: improved detection and functional classification of transfer RNA genes. Nucleic Acids Res. 2021;49(16):9077-9096. doi 10.1093/nar/gkab688Chan P.P., Lin B.Y., Mak A.J., Lowe T.M. tRNAscan-SE 2.0: improved detection and functional classification of transfer RNA genes. Nucleic Acids Res. 2021;49(16):9077-9096. doi 10.1093/nar/gkab688Chen W., Peng W., Wang R., Bai S., Cao M., Xiong S., Li Y., Yang Y., Liang J., Liu L., Yazdani H.O., Zhao Y., Cheng B. Exosome-derived tRNA fragments tRF-GluCTC-0005 promotes pancreatic cancer liver metastasis by activating hepatic stellate cells. Cell Death Dis. 2024;15(1):102. doi 10.1038/s41419-024-06482-3Chen W., Peng W., Wang R., Bai S., Cao M., Xiong S., Li Y., Yang Y., Liang J., Liu L., Yazdani H.O., Zhao Y., Cheng B. Exosome-derived tRNA fragments tRF-GluCTC-0005 promotes pancreatic cancer liver metastasis by activating hepatic stellate cells. Cell Death Dis. 2024;15(1):102. doi 10.1038/s41419-024-06482-3Dobin A., Davis C.A., Schlesinger F., Drenkow J., Zaleski C., Jha S., Batut P., Chaisson M., Gingeras T.R. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15-21. doi 10.1093/bioinformatics/bts635Dobin A., Davis C.A., Schlesinger F., Drenkow J., Zaleski C., Jha S., Batut P., Chaisson M., Gingeras T.R. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15-21. doi 10.1093/bioinformatics/bts635Figueroa-Santiago O., Espino A.M. Fasciola hepatica fatty acid binding protein induces the alternative activation of human macrophages. Infect Immun. 2014;82(12):5005-5012. doi 10.1128/IAI.02541-14Figueroa-Santiago O., Espino A.M. Fasciola hepatica fatty acid binding protein induces the alternative activation of human macrophages. Infect Immun. 2014;82(12):5005-5012. doi 10.1128/IAI.02541-14Flynn R.J., Irwin J.A., Olivier M., Sekiya M., Dalton J.P., Mulcahy G. Alternative activation of ruminant macrophages by Fasciola hepatica. Vet Immunol Immunopathol. 2007;120(1-2):31-40. doi 10.1016/j.vetimm.2007.07.003Flynn R.J., Irwin J.A., Olivier M., Sekiya M., Dalton J.P., Mulcahy G. Alternative activation of ruminant macrophages by Fasciola hepatica. Vet Immunol Immunopathol. 2007;120(1-2):31-40. doi 10.1016/j.vetimm.2007.07.003Fontenla S., Langleib M., de la Torre-Escudero E., Domínguez M.F., Robinson M.W., Tort J. Role of Fasciola hepatica small RNAs in the interaction with the mammalian host. Front Cell Infect Microbiol. 2022;11:812141. doi 10.3389/fcimb.2021.812141Fontenla S., Langleib M., de la Torre-Escudero E., Domínguez M.F., Robinson M.W., Tort J. Role of Fasciola hepatica small RNAs in the interaction with the mammalian host. Front Cell Infect Microbiol. 2022;11:812141. doi 10.3389/fcimb.2021.812141Hongsrichan N., Intuyod K., Pinlaor P., Khoontawad J., Yongvanit P., Wongkham C., Roytrakul S., Pinlaor S. Cytokine/chemokine secretion and proteomic identification of upregulated annexin A1 from peripheral blood mononuclear cells cocultured with the liver fluke Opisthorchis viverrini. Infect Immun. 2014;82(5):2135-2147. doi 10.1128/IAI.00901-13Hongsrichan N., Intuyod K., Pinlaor P., Khoontawad J., Yongvanit P., Wongkham C., Roytrakul S., Pinlaor S. Cytokine/chemokine secretion and proteomic identification of upregulated annexin A1 from peripheral blood mononuclear cells cocultured with the liver fluke Opisthorchis viverrini. Infect Immun. 2014;82(5):2135-2147. doi 10.1128/IAI.00901-13Jayaram A., Galande S., Sharbati S., Deshpande D., Pawar K. Profile of tRNA-derived short non-coding RNAs during monocyte differentiation and their role in macrophage survival. RNA Biol. 2025;22(1): 1-9. doi 10.1080/15476286.2025.2525886Jayaram A., Galande S., Sharbati S., Deshpande D., Pawar K. Profile of tRNA-derived short non-coding RNAs during monocyte differentiation and their role in macrophage survival. RNA Biol. 2025;22(1): 1-9. doi 10.1080/15476286.2025.2525886Khowawisetsut L., Vimonpatranon S., Lekmanee K., Sawasdipokin H., Srimark N., Chotivanich K., Pattanapanyasat K. Differential effect of extracellular vesicles derived from Plasmodium falciparum-infected red blood cells on monocyte polarization. Int J Mol Sci. 2023;24(3): 2631. doi 10.3390/ijms24032631Khowawisetsut L., Vimonpatranon S., Lekmanee K., Sawasdipokin H., Srimark N., Chotivanich K., Pattanapanyasat K. Differential effect of extracellular vesicles derived from Plasmodium falciparum-infected red blood cells on monocyte polarization. Int J Mol Sci. 2023;24(3): 2631. doi 10.3390/ijms24032631Kim E.M., Kwak Y.S., Yi M.H., Kim J.Y., Sohn W.M., Yong T.S. Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo. PLoS Negl Trop Dis. 2017;11(5):e0005614. doi 10.1371/journal.pntd.0005614Kim E.M., Kwak Y.S., Yi M.H., Kim J.Y., Sohn W.M., Yong T.S. Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo. PLoS Negl Trop Dis. 2017;11(5):e0005614. doi 10.1371/journal.pntd.0005614Kusakisako K., Nakao R., Katakura K. Detection of parasite-derived tRNA and rRNA fragments in the peripheral blood of mice experimentally infected with Leishmania donovani and Leishmania amazonensis using next-generation sequencing analysis. Parasitol Int. 2023;93:102716. doi 10.1016/j.parint.2022.102716Kusakisako K., Nakao R., Katakura K. Detection of parasite-derived tRNA and rRNA fragments in the peripheral blood of mice experimentally infected with Leishmania donovani and Leishmania amazonensis using next-generation sequencing analysis. Parasitol Int. 2023;93:102716. doi 10.1016/j.parint.2022.102716Lertjuthaporn S., Somkird J., Lekmanee K., Atipimonpat A., Sukapirom K., Sawasdipokin H., Tiewcharoen S., Pattanapanyasat K., Khowawisetsut L. Extracellular vesicles from Naegleria fowleri induce IL-8 response in THP-1 macrophage. Pathogens. 2022;11(6): 632. doi 10.3390/pathogens11060632Lertjuthaporn S., Somkird J., Lekmanee K., Atipimonpat A., Sukapirom K., Sawasdipokin H., Tiewcharoen S., Pattanapanyasat K., Khowawisetsut L. Extracellular vesicles from Naegleria fowleri induce IL-8 response in THP-1 macrophage. Pathogens. 2022;11(6): 632. doi 10.3390/pathogens11060632Li N., Yao S., Yu G., Lu L., Wang Z. tRFtarget 2.0: expanding the targetome landscape of transfer RNA-derived fragments. Nucleic Acids Res. 2024;52(5):345-350. doi 10.1093/nar/gkad815Li N., Yao S., Yu G., Lu L., Wang Z. tRFtarget 2.0: expanding the targetome landscape of transfer RNA-derived fragments. Nucleic Acids Res. 2024;52(5):345-350. doi 10.1093/nar/gkad815Li Y., Liu Y., Xiu F., Wang J., Cong H., He S., Shi Y., Wang X., Li X., Zhou H. Characterization of exosomes derived from Toxoplasma gondii and their functions in modulating immune responses. Int J Nanomedicine. 2018;13:467-477. doi 10.2147/IJN.S151110Li Y., Liu Y., Xiu F., Wang J., Cong H., He S., Shi Y., Wang X., Li X., Zhou H. Characterization of exosomes derived from Toxoplasma gondii and their functions in modulating immune responses. Int J Nanomedicine. 2018;13:467-477. doi 10.2147/IJN.S151110Lishai E., Pakharukova M. The liver fluke Opisthorchis felineus exosomal tRNA-derived small RNAs as potential mediators of host manipulation. Biomolecules. 2026;16(2):244. doi 10.3390/biom 16020244Lishai E., Pakharukova M. The liver fluke Opisthorchis felineus exosomal tRNA-derived small RNAs as potential mediators of host manipulation. Biomolecules. 2026;16(2):244. doi 10.3390/biom 16020244Lishai E.A., Zaparina O.G., Kapushchak Y.K., Sripa B., Hong S.J., Cheng G., Pakharukova M.Y. Comparative liver transcriptome analysis in hamsters infected with food-borne trematodes Opisthorchis felineus, Opisthorchis viverrini, or Clonorchis sinensis. PLoS Negl Trop Dis. 2024;18(12):e0012685. doi 10.1371/journal.pntd.0012685Lishai E.A., Zaparina O.G., Kapushchak Y.K., Sripa B., Hong S.J., Cheng G., Pakharukova M.Y. Comparative liver transcriptome analysis in hamsters infected with food-borne trematodes Opisthorchis felineus, Opisthorchis viverrini, or Clonorchis sinensis. PLoS Negl Trop Dis. 2024;18(12):e0012685. doi 10.1371/journal.pntd.0012685Liu J., Zhu L., Wang J., Qiu L., Chen Y., Davis R.E., Cheng G. Schistosoma japonicum extracellular vesicle miRNA cargo regulates host macrophage functions facilitating parasitism. PLoS Pathog. 2019; 15(6):e1007817. doi 10.1371/journal.ppat.1007817Liu J., Zhu L., Wang J., Qiu L., Chen Y., Davis R.E., Cheng G. Schistosoma japonicum extracellular vesicle miRNA cargo regulates host macrophage functions facilitating parasitism. PLoS Pathog. 2019; 15(6):e1007817. doi 10.1371/journal.ppat.1007817Liu Y., Li H., Czajkowsky D.M., Shao Z. Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes. Hereditas. 2021;158(1):43. doi 10.1186/s41065-021-00205-wLiu Y., Li H., Czajkowsky D.M., Shao Z. Monocytic THP-1 cells diverge significantly from their primary counterparts: a comparative examination of the chromosomal conformations and transcriptomes. Hereditas. 2021;158(1):43. doi 10.1186/s41065-021-00205-wLove M.I., Huber W., Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550. doi 10.1186/s13059-014-0550-8Love M.I., Huber W., Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550. doi 10.1186/s13059-014-0550-8Lu S., Wei X., Tao L., Dong D., Hu W., Zhang Q., Tao Y., Yu C., Sun D., Cheng H. A novel tRNA-derived fragment tRF-3022b modulates cell apoptosis and M2 macrophage polarization via binding to cytokines in colorectal cancer. J Hematol Oncol. 2022;15(1):176. doi 10.1186/s13045-022-01388-zLu S., Wei X., Tao L., Dong D., Hu W., Zhang Q., Tao Y., Yu C., Sun D., Cheng H. A novel tRNA-derived fragment tRF-3022b modulates cell apoptosis and M2 macrophage polarization via binding to cytokines in colorectal cancer. J Hematol Oncol. 2022;15(1):176. doi 10.1186/s13045-022-01388-zMann M., Wright P.R., Backofen R. IntaRNA 2.0: enhanced and customizable prediction of RNA-RNA interactions. Nucleic Acids Res. 2017;45(1):435-439. doi 10.1093/nar/gkx279Mann M., Wright P.R., Backofen R. IntaRNA 2.0: enhanced and customizable prediction of RNA-RNA interactions. Nucleic Acids Res. 2017;45(1):435-439. doi 10.1093/nar/gkx279Mordvinov V.A., Minkova G.A., Kovner A.V., Ponomarev D.V., Lvova M.N., Zaparina O., Romanenko S.A., Shilov A.G., Pakharukova M.Y. A tumorigenic cell line derived from a hamster cholangiocarcinoma associated with Opisthorchis felineus liver fluke infection. Life Sci. 2021;277:119494. doi 10.1016/j.lfs.2021.119494Mordvinov V.A., Minkova G.A., Kovner A.V., Ponomarev D.V., Lvova M.N., Zaparina O., Romanenko S.A., Shilov A.G., Pakharukova M.Y. A tumorigenic cell line derived from a hamster cholangiocarcinoma associated with Opisthorchis felineus liver fluke infection. Life Sci. 2021;277:119494. doi 10.1016/j.lfs.2021.119494Natali L., Luna Pizarro G., Moyano S., de la Cruz-Thea B., Musso J., Rópolo A.S., Eichner N., Meister G., Musri M.M., Feliziani C., Touz M.C. The exosome-like vesicles of Giardia assemblages A, B, and E are involved in the delivering of distinct small RNA from parasite to parasite. Int J Mol Sci. 2023;24(11):9559. doi 10.3390/ijms24119559Natali L., Luna Pizarro G., Moyano S., de la Cruz-Thea B., Musso J., Rópolo A.S., Eichner N., Meister G., Musri M.M., Feliziani C., Touz M.C. The exosome-like vesicles of Giardia assemblages A, B, and E are involved in the delivering of distinct small RNA from parasite to parasite. Int J Mol Sci. 2023;24(11):9559. doi 10.3390/ijms24119559Norouzi M., Pirestani M., Arefian E., Dalimi A., Sadraei J., Mirjalali H. Exosomes secreted by Blastocystis subtypes affect the expression of proinflammatory and anti-inflammatory cytokines (TNFα, IL-6, IL-10, IL-4). Front Med. 2022;9:940332. doi 10.3389/fmed.2022.940332Norouzi M., Pirestani M., Arefian E., Dalimi A., Sadraei J., Mirjalali H. Exosomes secreted by Blastocystis subtypes affect the expression of proinflammatory and anti-inflammatory cytokines (TNFα, IL-6, IL-10, IL-4). Front Med. 2022;9:940332. doi 10.3389/fmed.2022.940332Pakharukova M.Y., Pakharukov Y.V., Mordvinov V.A. Effects of miconazole/clotrimazole and praziquantel combinations against the liver fluke Opisthorchis felineus in vivo and in vitro. Parasitol Res. 2018;117(7):2327-2331. doi 10.1007/s00436-018-5895-6Pakharukova M.Y., Pakharukov Y.V., Mordvinov V.A. Effects of miconazole/clotrimazole and praziquantel combinations against the liver fluke Opisthorchis felineus in vivo and in vitro. Parasitol Res. 2018;117(7):2327-2331. doi 10.1007/s00436-018-5895-6Pakharukova M.Y., Samsonov V.A., Serbina E.A., Mordvinov V.A. A study of tribendimidine effects in vitro and in vivo on the liver fluke Opisthorchis felineus. Parasit Vectors. 2019;12(1):23. doi 10.1186/s13071-019-3288-zPakharukova M.Y., Samsonov V.A., Serbina E.A., Mordvinov V.A. A study of tribendimidine effects in vitro and in vivo on the liver fluke Opisthorchis felineus. Parasit Vectors. 2019;12(1):23. doi 10.1186/s13071-019-3288-zPakharukova M.Y., Savina E., Ponomarev D.V., Gubanova N.V., Zaparina O., Zakirova E.G., Cheng G., Tikhonova O.V., Mordvinov V.A. Proteomic characterization of Opisthorchis felineus exosome-like vesicles and their uptake by human cholangiocytes. J Proteomics. 2023;283-284:104927. doi 10.1016/j.jprot.2023.104927Pakharukova M.Y., Savina E., Ponomarev D.V., Gubanova N.V., Zaparina O., Zakirova E.G., Cheng G., Tikhonova O.V., Mordvinov V.A. Proteomic characterization of Opisthorchis felineus exosome-like vesicles and their uptake by human cholangiocytes. J Proteomics. 2023;283-284:104927. doi 10.1016/j.jprot.2023.104927Passos L.S., Gazzinelli-Guimarães P.H., Oliveira Mendes T.A., Guimarães A.C., Silveira Lemos D.D., Ricci N.D., Gonçalves R., Bartholomeu D.C., Fujiwara R.T., Bueno L.L. Regulatory monocytes in helminth infections: insights from the modulation during human hookworm infection. BMC Infect Dis. 2017;17(1):253. doi 10.1186/s12879-017-2366-0Passos L.S., Gazzinelli-Guimarães P.H., Oliveira Mendes T.A., Guimarães A.C., Silveira Lemos D.D., Ricci N.D., Gonçalves R., Bartholomeu D.C., Fujiwara R.T., Bueno L.L. Regulatory monocytes in helminth infections: insights from the modulation during human hookworm infection. BMC Infect Dis. 2017;17(1):253. doi 10.1186/s12879-017-2366-0Prehn J.H.M., Jirström E. Angiogenin and tRNA fragments in Parkinson’s disease and neurodegeneration. Acta Pharmacol Sin. 2020; 41(4):442-446. doi 10.1038/s41401-020-0375-9Prehn J.H.M., Jirström E. Angiogenin and tRNA fragments in Parkinson’s disease and neurodegeneration. Acta Pharmacol Sin. 2020; 41(4):442-446. doi 10.1038/s41401-020-0375-9Rehmsmeier M., Steffen P., Hochsmann M., Giegerich R. Fast and effective prediction of microRNA/target duplexes. RNA. 2004;10(10): 1507-1517. doi 10.1261/rna.5248604Rehmsmeier M., Steffen P., Hochsmann M., Giegerich R. Fast and effective prediction of microRNA/target duplexes. RNA. 2004;10(10): 1507-1517. doi 10.1261/rna.5248604Saltykova I.V., Ogorodova L.M., Bragina E.Y., Puzyrev V.P., Freidin M.B. Opisthorchis felineus liver fluke invasion is an environmental factor modifying genetic risk of atopic bronchial asthma. Acta Trop. 2014;139:53-56. doi 10.1016/j.actatropica.2014.07.004Saltykova I.V., Ogorodova L.M., Bragina E.Y., Puzyrev V.P., Freidin M.B. Opisthorchis felineus liver fluke invasion is an environmental factor modifying genetic risk of atopic bronchial asthma. Acta Trop. 2014;139:53-56. doi 10.1016/j.actatropica.2014.07.004Sánchez-López C.M., González-Arce A., Soler C., Ramírez-Toledo V., Trelis M., Bernal D., Marcilla A. Extracellular vesicles from the trematodes Fasciola hepatica and Dicrocoelium dendriticum trigger different responses in human THP-1 macrophages. J Extracell Vesicles. 2023;12(4):e12317. doi 10.1002/jev2.12317Sánchez-López C.M., González-Arce A., Soler C., Ramírez-Toledo V., Trelis M., Bernal D., Marcilla A. Extracellular vesicles from the trematodes Fasciola hepatica and Dicrocoelium dendriticum trigger different responses in human THP-1 macrophages. J Extracell Vesicles. 2023;12(4):e12317. doi 10.1002/jev2.12317Silverman J.M., Clos J., Horakova E., Wang A.Y., Wiesgigl M., Kelly I., Lynn M.A., McMaster W.R., Foster L.J., Levings M.K., Reiner N.E. Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. J Immunol. 2010;185(9):5011-5022. doi 10.4049/jimmunol.1000541Silverman J.M., Clos J., Horakova E., Wang A.Y., Wiesgigl M., Kelly I., Lynn M.A., McMaster W.R., Foster L.J., Levings M.K., Reiner N.E. Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. J Immunol. 2010;185(9):5011-5022. doi 10.4049/jimmunol.1000541Strømme O., Heck K.A., Brede G., Lindholm H.T., Otterlei M., Arum C.J. tRNA-derived fragments as biomarkers in bladder cancer. Cancers. 2024;16(8):1588. doi 10.3390/cancers16081588Strømme O., Heck K.A., Brede G., Lindholm H.T., Otterlei M., Arum C.J. tRNA-derived fragments as biomarkers in bladder cancer. Cancers. 2024;16(8):1588. doi 10.3390/cancers16081588Twu O., de Miguel N., Lustig G., Stevens G.C., Vashisht A.A., Wohlschlegel J.A., Johnson P.J. Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host:parasite interactions. PLoS Pathog. 2013;9(7):e1003482. doi 10.1371/journal.ppat.1003482Twu O., de Miguel N., Lustig G., Stevens G.C., Vashisht A.A., Wohlschlegel J.A., Johnson P.J. Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host:parasite interactions. PLoS Pathog. 2013;9(7):e1003482. doi 10.1371/journal.ppat.1003482Valinezhad Orang A., Safaralizadeh R., Kazemzadeh-Bavili M. Mechanisms of miRNA-mediated gene regulation from common downregulation to mRNA-specific upregulation. Int J Genomics. 2014;2014: 970607. doi 10.1155/2014/970607Valinezhad Orang A., Safaralizadeh R., Kazemzadeh-Bavili M. Mechanisms of miRNA-mediated gene regulation from common downregulation to mRNA-specific upregulation. Int J Genomics. 2014;2014: 970607. doi 10.1155/2014/970607Xia J., Jiang S.C., Peng H.J. Association between liver fluke infection and hepatobiliary pathological changes: a systematic review and meta-analysis. PloS One. 2015;10(7):e0132673. doi 10.1371/journal.pone.0132673Xia J., Jiang S.C., Peng H.J. Association between liver fluke infection and hepatobiliary pathological changes: a systematic review and meta-analysis. PloS One. 2015;10(7):e0132673. doi 10.1371/journal.pone.0132673Yu G., Wang L.G., Han Y., He Q.Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-287. doi 10.1089/omi.2011.0118Yu G., Wang L.G., Han Y., He Q.Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-287. doi 10.1089/omi.2011.0118Zhang X., Duan S., Li X., Ding J., Zuo L., Sun B., Zhang X., Jiang X., Gao Y., Hu X., Han S. Differences in the secretory exosomes of Clonorchis sinensis adults at different incubation times. Acta Trop. 2022; 234:106604. doi 10.1016/j.actatropica.2022.106604Zhang X., Duan S., Li X., Ding J., Zuo L., Sun B., Zhang X., Jiang X., Gao Y., Hu X., Han S. Differences in the secretory exosomes of Clonorchis sinensis adults at different incubation times. Acta Trop. 2022; 234:106604. doi 10.1016/j.actatropica.2022.106604

The authors declare that there are no conflicts of interest present.