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Up-regulated micrornas in blastocoel fluid of human implanted embryos could control circuits of pluripotency and be related to embryo competence

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JOURNAL OF ASSISTED REPRODUCTION AND GENETICS 2025年 1-15页

作者： Battaglia, Rosalia Caponnetto, Angela Ferrara, Carmen Fazzio, Anna Barbagallo, Cristina Stella, Michele Barbagallo, Davide Ragusa, Marco Vento, Maria Elena Borzi, Placido Scollo, Paolo Carli, Luca Feichtinger, Michael Kasapi, Evangelia Tsakos, Elias Palini, Simone Sierka, Wojciech Pecorino, Basilio Campitiello, Maria Rosaria Ronsini, Carlo Purrello, Michele Valerio, Domenico Longobardi, Salvatore D'Hooghe, Thomas Di Pietro, Cinzia Univ Catania Dept Biomed & Biotechnol Sci Sect Biol & Genet G Sichel I-95123 Catania Italy Univ Enna Kore Dept Med & Surg I-94100 Enna Italy Cannizzaro Hosp IVF Unit Catania Italy Wunschbaby Inst Feichtinger Vienna Austria EmbryoClin IVF Thessaloniki Greece Cervesi Hosp IVF Unit Cattolica Italy Gyncentrum Sp Zelazna 1 PL-40851 Katowice Poland ASL Salerno Dept Obstet & Gynecol & Physiopathol Human Reprod Salerno Italy Univ Campania Luigi Vanvitelli Dept Woman Child & Gen & Specialized Surg Naples Italy Inst Genet Res IRG I-80143 Naples Italy Merck Serono SpA Global Clin Dev Rome Italy Merck KGaA Darmstadt Germany KU Leuven Univ Leuven Dept Dev & Regenerat Biomed Sci Grp Leuven Belgium

Purpose The paper aims to investigate the biological role of micrornas secreted by preimplantation embryo into the blastocoel fluid and to detect a distinctive molecular signature for identifying embryos with the highest implantation potential. Methods We carried on a multicenter retrospective study involving five European IVF centers. We collected 112 blastocoel fluid samples from embryos on day 5 post-fertilization, cultured individually, along with data on blastocyst grade and embryo transfer outcomes. Using a custom TLDA Array, we compared the expression levels of 89 miRNAs between 33 fluids from high-quality implanted embryos and 30 fluids from high-quality not-implanted embryos. Expression differences were assessed using SAM and t-test. Additionally, correlation and function enrichment analysis and network construction were conducted to identify the biological roles of deregulated micrornas. Results We identified six up-regulated micrornas in the blastocoel fluid from implanted embryos, significantly and positively correlated across all samples (r >= 0.7;P <= 0.05). They could take part in pluripotency circuits, regulating and being regulated by transcription factors associated with stemness, cell growth, and embryo development. The ROC curve analysis confirmed the potential of these miRNAs as implantation classifiers. Conclusion The six miRNAs up-regulated in blastocoel fluid from implanted embryos may represent a functional molecular signature for evaluating blastocyst quality and identifying the most competent embryos. Their evaluation associated with non-invasive preimplantation genetic testing, integrating epigenetic and genomic analyses, could enhance implantation grade and allow for identification of the euploid embryo not able to implant.

关键词： Blastocoel fluid Embryo development Embryo implantation Human blastocyst micrornas

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Skin regenerative potential of hydrogel matrices incorporated with stem cell-derived extracellular vesicles enriched with micrornas: a systematic review

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MOLECULAR AND CELLULAR BIOCHEMISTRY 2025年 1-33页

作者： Miao, Xiaolei Davoudi, Maryam Sadegh-Nejadi, Sahar Ghahari, Seyed Arsalan Bagherieh, Molood Afrisham, Reza Hubei Univ Sci & Technol Xianning Med Coll Sch Pharm Hubei Key Lab Diabet & Angiopathy Xianning 437100 Hubei Peoples R China Univ Tehran Med Sci Sch Allied Med Sci Dept Med Lab Sci Tehran Iran Univ Tehran Med Sci Sch Med Dept Clin Biochem Tehran Iran Mazandaran Univ Med Sci Ramsar Campus Ramsar Iran

Stem cell-derived extracellular vesicles (SC-EVs) are one huge promise in skin regenerative medicine, similar in advantages to stem cells with low immunerejection and tumor formations. These microvesicles are laden with micrornas, which assist in wound healing via angiogenesis and immune modulation. However, quick degradation and poor cellular uptake limit their regenerative capacity. Thanks to their adjustable characteristics, hydrogels can act as vehicles for transporting and sustainably releasing miRNA-SC-EVs at injury sites. Therefore, a systematic literature review was conducted on miRNA-enriched SC-EVs incorporated into hydrogels in animal skin regeneration models published from 2010 to 2024 (PROSPERO ID: CRD42024588072). Out of the 89 records, 12 met the criteria. Diabetic wounds are characterized by chronic inflammation, oxidative stress, and defective macrophage polarization, resulting in less satisfactory regeneration. The hydrogels tackled these issues by shifting macrophages from a pro-inflammatory M1 phenotype to a healing M2 phenotype, promoting collagen production, enhancing fibroblast movement, and boosting angiogenesis. Burn injuries frequently lead to slow recovery due to hypertrophic scarring, extended inflammation, and infection. Hyaluronic acid (HA)-derived hydrogels, infused with miR-21-5p and surface-treated with polydopamine and cationic antimicrobial peptides, promoted wound healing by lowering scarring and demonstrating anti-inflammatory, anti-apoptotic, and pro-angiogenic characteristics. The cell adhesion of these hydrogels can be enhanced by adding MOFs, chitosan, and extracellular matrix elements. The application of stimulus-responsive or stage-specific hydrogels is another mode of targeted healing. Further research and clinical trials will enhance the wound-healing efficiency of hybrid hydrogels.

关键词： Skin Wound healing Stem cells Extracellular vesicles micrornas Hydrogels

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NIR-II DNA Nanodevice for Spatiotemporal micrornas Imaging Based on "and" Logic-Gate Strategy

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ADVANCED FUNCTIONAL MATERIALS 2025年

作者： Li, Lei Zhang, Baochun Wang, Yifan Han, Hui Chen, Kai Li, Meixing Fan, Quli Zhang, Hui Shen, Qingming Nanjing Univ Posts & Telecommun Inst Adv Mat IAM State Key Lab Flexible Elect LoFE Nanjing 210023 Peoples R China Nanjing Univ Posts & Telecommun Inst Adv Mat IAM Jiangsu Key Lab Biosensors Nanjing 210023 Peoples R China Nanjing Normal Univ Sch Chem & Mat Sci Jiangsu Key Lab New Power Batteries Nanjing 210023 Peoples R China

The precise detection of multiple micrornas (miRNAs) is of great significance to the classification of various cell subtypes. However, miRNA detection is hindered by signal leakage, false-positive signals and low expression of miRNAs. Herein, a DNA nanodevice in the second near infrared region (NIR-II, 1000-1700 nm) (DND-II) is developed for dual miRNAs bioimaging based on "AND" logic-gate signal amplification strategy. The spatiotemporally controlled logic-gate-based DND-II is fabricated by thermosensitive liposomes integrated with the second near-infrared DNA probes. In particular, the "always-on" photoacoustic signal of DNA probes provided an additional imaging tool to monitor the distribution of DND-II in vivo. When both miRNAs are present, the DNA probes generated a "turn on" fluorescent signal through DNA logical analysis and molecular computation, further triggering an entropy-driven dual-cycle fluorescence signal amplification. The spatiotemporal DND-II provides a powerful platform for early diagnosis and photothermal ablation of different subtypes of tumor cells.

关键词： DNA nanodevice logic gate circuit micrornas NIR-II fluorescence imaging spatiotemporal activation

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Identification and differential expression analysis of micrornas in the liver and spleen tissues of Yunnan Zebu and Holstein cattle

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TROPICAL ANIMAL HEALTH AND PRODUCTION 2025年第2期57卷 1-14页

作者： Liu, Rong Liu, Hesong Li, Rong Li, Chunqing Xiao, Heng Chen, Shanyuan Yunnan Univ Sch Ecol & Environm Sci Kunming 650500 Peoples R China Yunnan Univ Sch Life Sci Kunming 650500 Peoples R China Yunnan Normal Univ Coll Life Sci Kunming 650500 Peoples R China

Extensive research has shown that miRNAs play a crucial role in regulating biological processes within organisms. This study analyzed miRNAs differentially expressed and potentially associated with immune function and tissue-specific expression in Yunnan Zebu and Holstein cattle. To achieve this, 20 liver and spleen tissue samples from the two cattle breeds were collected for high-throughput miRNA sequencing, with the liver tissue as a reference. The findings revealed that bta-miR-122 and bta-miR-143 are the most abundantly expressed known miRNAs in the liver and spleen tissues of Yunnan Zebu and Holstein cattle, respectively. Additionally, AC_000181.1_27195 and AC_000168.1_14386 emerged as the most highly expressed novel miRNAs in these tissues, exhibiting significant homology with human hsa-miR-3591-3p and hsa-miR-126-3p, respectively. Six differentially expressed miRNAs were selected for validation using stem-loop RT-qPCR, and the results were largely consistent with the high-throughput sequencing data. Functional enrichment analysis of the target genes of these known miRNAs revealed their association with critical metabolic and immune-related pathways in cattle, such as the insulin pathway, mTOR signaling, IFN-gamma pathway, and signaling mechanisms mediated by IL5 and IL3. These results enriched the miRNA database for liver and spleen tissues of Yunnan Zebu and Holstein cattle.

关键词： Yunnan Zebu Holstein cattle micrornas Immune function Differential expression High-throughput sequencing

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Therapeutic prospects of micrornas derived from mesenchymal stem cell extracellular vesicles in rheumatoid arthritis: a comprehensive overview

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MOLECULAR AND CELLULAR BIOCHEMISTRY 2025年第3期480卷 1275-1286页

作者： Akbarzadeh, Armin Gerami, Mohammad Hadi Farrokhi, Majid Reza Shapoori, Shima Jafarinia, Morteza Shiraz Univ Med Sci Sch Med Dept Orthoped Surg Shiraz Iran Shiraz Univ Med Sci Shiraz Neurosci Res Ctr Shiraz Iran Shiraz Univ Med Sci Dept Neurosurg Shiraz Iran Univ Galway Ctr Res Med Devices CURAM Galway Ireland

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammatory joint damage. Recent studies have focused on the significance of micrornas (miRNAs) in the pathogenesis of RA. Mesenchymal stem cells (MSCs) have emerged as a potential therapeutic option for RA based on their regenerative and immunomodulatory properties. MSCs release extracellular vesicles (EVs) containing miRNAs that can modulate immune and inflammatory responses. This article provides a comprehensive overview of the current evidence on the existence of various MSCs-derived miRNAs involved in the pathophysiology, characterization, and treatment of RA. An overview of the miRNA profiles in MSC-EVs is provided, along with an examination of their impact on various cell types implicated in RA pathogenesis, including synovial fibroblasts, macrophages, and T cells. Furthermore, the therapeutic capability of MSC-EVs for miRNA-based therapies in RA is discussed. In total, this review can present an extensive view of the complex interaction between EVs and MSC-derived miRNAs in RA and thus suggest valuable strategies for developing new therapeutic approaches to target this debilitating disease.

关键词： Mesenchymal stem cells Rheumatoid arthritis micrornas Extracellular vesicles Exosome

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Classification and Prognostication of B-Cell and T-Cell Multicentric Lymphoma in Dogs Using Serum micrornas

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VETERINARY AND COMPARATIVE ONCOLOGY 2025年第0期 2025 Apr 5页

作者： Ludwig, Latasha Treleaven, Heather Moorehead, Roger Foster, Robert A. Wood, R. Darren Ali, R. Ayesha Wood, Geoffrey A. Univ Guelph Dept Pathobiol Guelph ON Canada Cornell Univ Dept Populat Med & Diagnost Sci Ithaca NY USA Univ Guelph Dept Biomed Sci Guelph ON Canada Univ Guelph Dept Math & Stat Guelph ON Canada

Canine multicentric lymphoma is a common malignancy in dogs. It often responds well to initial chemotherapy but frequently relapses and has a poor response to subsequent treatment. B-cell (BCL) and T-cell (TCL) lymphomas differ in both their prognoses and chemotherapeutic treatment protocols. Currently, immunophenotyping can be costly and can only be performed on specific high-quality samples. micrornas (miRNAs) are small molecules present in blood and tissues and are dysregulated in both human and canine lymphoma. We investigated 59 miRNAs by RT-qPCR to establish a serum miRNA profile in dogs with B-cell and T-cell multicentric lymphoma. Multiple miRNA pruned decision tree models were used to classify BCL and TCL cases from each other and controls, and to predict prognosis in BCL cases receiving standard CHOP chemotherapy. Six individual miRNAs were differentially expressed in serum between BCL and controls, and three were differentially expressed between BCL and TCL. A three-miRNA model (miR-155-5p, miR-1 and miR-181b) could differentiate between BCL, TCL and control samples with an accuracy of 83.02%. A three-miRNA model (miR-125b-5p, miR-350 and let-7b-5p) in BCL samples separated the cases into four groups with hazard ratios ranging from 0.44 to 3.5 for overall survival. This study established a serum miRNA profile for both BCL and TCL and demonstrated the utility of multiple serum miRNA models to assist in the diagnosis of lymphoma and BCL prognostication.

关键词： dog lymphoma micrornas serum

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Physiological and cellular mechanisms of ischemic preconditioning micrornas-mediated in underlying of ischemia/reperfusion injury in different organs

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MOLECULAR AND CELLULAR BIOCHEMISTRY 2025年第2期480卷 855-868页

作者： Gheitasi, Izadpanah Akbari, Ghaidafeh Savari, Feryal Yasuj Univ Med Sci Fac Med Dept Physiol Yasuj Iran Shoushtar Fac Med Sci Dept Med Basic Sci Shoushtar Iran

Ischemia-reperfusion (I/R) injury, as a pathological phenomenon, takes place when blood supply to an organ is disrupted and then aggravated during restoration of blood flow. Ischemic preconditioning (IPC) is a potent method for attenuating subsequent events of IR damage in numerous organs. IPC protocol is determined by a brief and sequential time periods of I/R before the main ischemia. micrornas are endogenous non-coding RNAs that regulate post-transcriptionally target mRNA translation via degrading it and/or suppressing protein synthesis. This review introduces the physiological and cellular mechanisms of ischemic preconditioning micrornas-mediated after I/R insult in different organs such as the liver, kidney, heart, brain, and intestine. Data of this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2023. Based on these literature studies, IPC/IR intervention can affect cellular mechanisms including oxidative stress, apoptosis, angiogenesis, and inflammation through up-regulation or down-regulation of multiple micrornas and their target genes.

关键词： Ischemia/reperfusion injury Ischemic preconditioning micrornas

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Regulation of Apoptotic Pathways by micrornas: A Therapeutic Strategy for Alzheimer's Disease

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MOLECULAR NEUROBIOLOGY 2025年 1-37页

作者： Saadh, Mohamed J. Muhammad, Faris Anad Alazzawi, Tuqa S. Fahdil, Ali A. Athab, Zainab H. Tuxtayev, Jamshid Alsaikhan, Fahad Farhood, Bagher Middle East Univ Fac Pharm Amman 11831 Jordan Al Noor Univ Coll Dept Pharm Nineveh Iraq Natl Univ Sci & Technol Coll Dentist Dhi Qar Iraq Al Farahidi Univ Med Tech Coll Baghdad Iraq Al Zahrawi Univ Coll Dept Pharm Karbala Iraq Samarkand State Med Inst Fac Pediat Dept Surg Dis Samarkand Uzbekistan Prince Sattam Bin Abdulaziz Univ Coll Pharm Alkharj Saudi Arabia Ibn Sina Natl Coll Med Studies Sch Pharm Jeddah Saudi Arabia Kashan Univ Med Sci Fac Paramed Sci Dept Med Phys & Radiol Kashan Iran

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder marked by a gradual decline in memory and cognitive functions. It is characterized by the presence of senile plaques, neurofibrillary tangles, and neuronal degeneration, affecting a significant portion of the human population. A key feature of various nervous system disorders, including AD, is extensive cellular death caused by apoptosis, which affects not only neurons but also glial cells. While apoptosis plays a vital role in eliminating certain cells and supporting normal development, alterations or disruptions in apoptotic pathways can lead to harmful neurodegenerative conditions such as AD. Thus, targeting apoptosis presents a promising therapeutic approach for these diseases. micrornas (miRNAs), a class of non-coding RNA, play diverse roles in cellular functions, including proliferation, gene expression regulation, programmed cell death, intercellular communication, and angiogenesis. By modulating regulatory genes, miRNAs can influence apoptosis, either promoting or inhibiting it. Aberrant expression of miRNAs can impact multiple apoptotic pathways, potentially driving the progression of AD and related health issues. This review summarizes recent research on miRNAs and their dual role in exacerbating or protecting against neural cell damage in AD by altering apoptotic pathways. The regulation of apoptosis by miRNAs offers a prospective therapeutic strategy for Alzheimer's disease.

关键词： Apoptosis Alzheimer's disease micrornas Non-coding RNAs

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micrornas unveiled:Nobel recognition of a revolutionary gene regulation mechanism

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hLife 2025年第1期3卷 1-4页

作者： Junchao Xue Gangming Zhang Enzhi Shen Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province School of Life SciencesWestlake UniversityZhejiangChina Westlake Laboratory of Life Sciences and Biomedicine ZhejiangChina Institute of Biology Westlake Institute for Advanced StudyZhejiangChina RNA Therapeutics Institute University of Massachusetts Medical SchoolMassachusettsUSA

A NOBEL FOR MICRORNA The 2024 Nobel Prize in physiology or medicine honors Victor Ambros and Gary Ruvkun for their groundbreaking discovery of micrornas(miRNAs),a unique class of small RNA molecules that play a critical role in gene regulation across multicellular *** discovery unveiled a novel mechanism in gene expression control,which is now understood as fundamental to the functioning and development of diverse species,including humans.

关键词： Nobel mechanism micrornas

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Estimate of circRNAs and micrornas synergies on clinical advance of psoriasis

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Journal of Immunoassay and Immunochemistry 2025年第2期46卷 147-168页

作者： Saleh, Amany A. Tayel, Safaa I. Shehata, Wafaa A. El-Masry, Eman A. Abd-Elhafiz, Huda I. Elhelbawy, Mohammed G. EL-Naidany, Sherin S. Medical Biochemistry and Molecular Biology Department Faculty of Medicine Menoufia University Al Minufiyah Egypt Medical Surgical Nursing Department College of Nursing Taibah University KSA Medina Saudi Arabia Medical Biochemistry Unit College of Medicine Albaha University Albaha Saudi Arabia Dermatology and Andrology & STDs Department Faculty of Medicine Menoufia University Al Minufiyah Egypt Department of Medical Microbiology and Immunology Faculty of Medicine Menoufia University Al Minufiya Egypt Microbiology and Immunology Unit Department of Pathology College of Medicine Jouf University Sakaka Saudi Arabia Clinical Pharmacology Department Faculty of Medicine Menoufia University Al Minufiyah Egypt Clinical Pathology Department Faculty of Medicine Menoufia University Al Minufiyah Egypt

Background: Noncoding RNAs have recently proven their contributing role in the pathogenesis of numerous diseases. The etiology of psoriasis is still not well defined, and genetic and environmental factors are blamed. We meant to explore the association of circRNAs/micrornas in psoriasis and inspect their correlation with the clinical features of the disease. Design and Methods: This study included 166 subjects: 83 cases with plaque psoriasis and 83 age- and sex-matched healthy persons as the control group. The expression levels of circRNA000102, circRNA0045272, circRNA0084764, and micrornas -93,181, 16a, and 21 were estimated by quantitative real-time PCR. Results: CircRNA0045272 was ten-fold up-regulated, whereas circRNA0084764 and circRNA000102 were about two-fold downregulated in patients vs. control. micrornas −93 and 181 were significantly downregulated in patients vs. control, whereas microRNA −16a and 21 were up-regulated in patients vs. control. CircRNA0045272 was positively correlated with microRNA 181, and circRNA0084764 was positively correlated with microRNA 93 and microRNA 181. CircRNA0045272 had the highest sensitivity (98.8%) and specificity (93.98%), and microRNA-16a had sensitivity (98.80%) with specificity (93.98%). Conclusion: We assume that circRNAs can predict psoriasis occurrence and progression by sponging a set of micrornas and can modulate several genes that disturb immune cell balance and inflammatory elements in psoriasis. © 2024 Taylor & Francis Group, LLC.

关键词： CircRNAs immune micrornas PCR psoriasis

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