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The leading form of cancer affecting females globally is breast cancer, characterized by an unregulated growth of cells within the breast. Therefore, examining breast tissue is crucial in accurately identifying and treating this disease. Exosomes are very small enclosures bounded by a layer of cells and produced by a variety of cells present in the cancerous tissue surroundings. They play a crucial role in several biological functions in cancerous tumors. These exosomes carry non-coding RNAs (ncRNAs) and are discharged into the TME, where they are instrumental in the development and advancement of tumors. Additionally, the ncRNAs enclosed in exosomes act as significant mediators of communication within cells. Consequently, there is limited comprehension regarding the precise roles and targets of exosomal RNA in regulation, as research in this area is still in its preliminary phases. This piece provides a comprehensive overview of the latest studies on exosomes, delving into their impact on the behavior of cancer cells and immune cells. Moreover, it presents a compilation of the diverse forms of non-coding RNA molecules found in exosomes released by both cancerous and supportive cells, including circular RNAs, microRNAs, and long non-coding RNAs. Current research has proven the noteworthy influence that non-coding RNA molecules have on the progression, proliferation, drug resistance, and immune responses of breast cancer cells., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Circular RNAs (circRNAs) have been identified to be dysregulated in non-small cell lung cancer (NSCLC) and implicated in the progression of this cancer. Here, this work aimed to investigate the role and mechanism of circ_0082374 on NSCLC progression. Levels of circ_0082374, miR-491-5p, GPX4 (glutathione peroxidase 4) and epithelial-mesenchymal transition (EMT)-related proteins were examined by quantitative real-time PCR or western blotting, respectively. Cell proliferation and metastasis were detected using cell counting kit-8, colony formation, EdU, transwell, and Scratch assays. Cell ferroptosis was evaluated by measuring cell survival after the treatment of different ferroptosis inducers or inhibitors, as well as the accumulation of intracellular reactive oxygen species (ROS), ferrous iron (Fe 2+ ) and malondialdehyde (MDA). The binding between miR-491-5p and circ_0082374 or GPX4 was confirmed using dual-luciferase reporter and RNA pull-down assays. In vivo experiments were conducted using murine xenograft assay and immunohistochemistry. Circ_0082374 was a stable circRNA with high expression in NSCLC tissues and cells. Functionally, circ_0082374 silencing suppressed NSCLC cell proliferation and metastasis. Moreover, its down-regulation enhanced ferroptosis by decreasing iron and lipid peroxidation accumulation. Mechanistically, circ_0082374 could indirectly up-regulate GPX4 expression via miR-491-5p, indicating the circ_0082374/miR-491-5p/GPX4 competitive endogenous RNAs (ceRNA) network. Rescue experiments demonstrated that the miR-491-5p/GPX4 axis mediated the regulatory effects of circ_0082374 exerted on NSCLC cells. Moreover, knockdown of circ_0082374 impeded NSCLC growth and EMT via regulating miR-491-5p and GPX4. Circ_0082374 silencing could suppress NSCLC cell proliferation, metastasis and induce ferroptosis through miR-491-5p/GPX4 axis, suggesting a novel therapeutic approach for NSCLC patients., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest. Ethical Approval and Consent to Participate: Written informed consents were obtained from all participants and this study was permitted by the Ethics Committee of Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College. The animal study has obtained the assent of the Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College Animal Care and Use Committee. Research Involving Human and Animal Rights: Animal studies were performed in compliance with the ARRIVE guidelines and the Basel Declaration. All animals received humane care according to the National Institutes of Health (USA) guidelines. Consent for Publication: Written informed consents were obtained from all participants., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Acute myocardial infarction (AMI) is one of the critical health conditions often caused by the rupture of unstable coronary artery plaque, triggering a series of events, such as platelet activation, thrombus formation, coronary artery blockage, lasted severe ischemia, and hypoxia in cardiomyocytes, and culminating in cell death. Platelet-derived microvesicles (PMVs) act as intermediates for cellular communication. Nevertheless, the role of PMVs in myocardial infarction remains unclear. Initially, AMI-related messenger ribose nucleic acid (mRNA) and micro RNA (miRNA) datasets from the Gene Expression Omnibus (GEO) database were analyzed, specifically focusing on the expressed genes associated with Ferroptosis. Further, a miRNA-mRNA regulatory network specific to AMI was constructed. Then, the effect of PMVs on cardiomyocyte survival was further confirmed through in vitro experiments. High ACSL1 expression was observed in the platelets of AMI patients. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that ACSL1, located in the mitochondria, played a key role in the PPAR signaling pathway. The elevated ACSL1 expression in a co-culture model of PMVs and AC16 cardiomyocytes significantly increased the AC16 cell Ferroptosis. Further, we validated that the platelet ACSL1 expression could be regulated by hsa-miR-449a. Together, these findings suggested that platelet ACSL1 could trigger myocardial cell death via PMV transport. In addition, this research provided a theoretical framework for attenuating myocardial cell Ferroptosis in patients with acute myocardial infarction., Competing Interests: Declarations. Competing interest: The authors declare that they have no conflict of interest. Ethics Approval and Consent to Participate: Written informed consent was obtained from each patient included in the study and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the Ethics Committee of First Hospital of Qinhuangdao. Consent for Publication: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Long noncoding RNA (lncRNA) plays a key role in regulating cancer development. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumor. The work was designed to further investigate the mechanism of action of DGUOK-AS1 in lung squamous cell carcinoma (LUSC). DGUOK-AS1 level in LUSC cells was measured using RT-qPCR. Counting Kit-8 assays and colony forming assays were performed to evaluate LUSC cell viability and proliferation. Transwell assays were performed to detect cell migration and invasion. Luciferase reporter and RNA pulldown assays were used to verify the binding capacity of DGUOK-AS1 and miR-653-5p. RNA immunoprecipitation assays were performed to verify the relationship of DGUOK-AS1, miR-653-5p, and SLC6A15. DGUOK-AS1 was highly expressed in LUSC cells. DGUOK-AS1 knockdown suppressed LUSC cell proliferation, migration, and invasion. SLC6A15 was demonstrated to be targeted by miR-653-5p, and DGUOK-AS1 interacted with miR-653-5p to modulate SLC6A15 level in LUSC cells. Overexpression of SLC6A15 reversed the suppressive effects of DGUOK-AS1 knockdown on LUSC cell processes. In conclusion, DGUOK-AS1 promotes malignant behaviors of LUSC cells by upregulating SLC6A15 level through interaction with miR-653-5p., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In hepatic fibrosis (HF), hepatic stellate cells (HSCs) form the extracellular matrix (ECM), and the pathological accumulation of ECM in the liver leads to inflammation. Our previous research found that miR-324-3p was down-regulated in culture-activated human HSCs. However, the precise effect of miR-324-3p on HF has not been elucidated. In this study, the HF mouse models were induced through directly injecting carbon tetrachloride (CCl 4 ) into mice; the HF cell models were constructed using TGF-β1-treated LX-2 cells. Next, real-time-quantitative polymerase chain reaction (RT-qPCR), western blot (WB) and immunohistochemistry (IHC) were applied to assess the expression levels of miR-324-3p, α-smooth muscle actin (α-SMA), Vimentin or SMAD4; hematoxylin and eosin (H&E), Masson' s trichrome and Sirius red staining to evaluate the liver injury; luciferase reporter assay to verify the targeting relationship between miR-324-3p and SMAD4; enzyme-linked immunosorbent assay (ELISA) to determine the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and cell counting kit-8 (CCK-8) and flow cytometry to evaluate the effects of miR-324-3p on cell proliferation and cycle/apoptosis, respectively. The experimental results showed a reduction in miR-324-3p level in CCl 4 -induced HF mice as well as transforming growth factor (TGF)-β1-activated HSCs. Interestingly, the miR-324-3p level was rescued following the HF recovery process. In HF mice induced by CCl 4 , miR-324-3p overexpression inhibited liver tissue damage, decreased serum ALT and AST levels, and inhibited fibrosis-related biomarkers (α-SMA, Vimentin) expression, thereby inhibiting HF. Similarly, miR-324-3p overexpression up-regulated α-SMA and Vimentin levels in HF cells, while knockdown of miR-324-3p had the opposite effect. Besides, miR-324-3p played an antifibrotic role through inhibiting the proliferation of hepatocytes. Further experiments confirmed that miR-324-3p targeted and down-regulated SMAD4 expression. SMAD4 was highly expressed in HF cells, and silencing SMAD4 significantly decreased the α-SMA and Vimentin levels in HF cells. Collectively, the miR-324-3p may suppress the activation of HSCs and HF by targeting SMAD4. Therefore, miR-324-3p is identified as a potential and novel therapeutic target for HF., Competing Interests: Declarations. Conflict of interests: The authors declare no conflict of interest. Ethical Approval: The Ethics Committee of Anhui Medical University for Animal Experimentation approved the experiments (LISC20190608)., (© 2024. The Author(s).)

Pancreatic adenocarcinoma (PAAD) is a fatal disease with poor survival. Increasing evidence show that hypoxia-induced exosomes are associated with cancer progression. Here, we aimed to investigate the function of hsa_circ_0007678 (circR3HCC1L) and hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD progression. Through the exoRBase 2.0 database, we screened for a circular RNA circR3HCC1L related to PAAD. Changes of circR3HCC1L in PAAD samples and cells were analyzed with real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration, invasion were analyzed by colony formation, cell counting, and transwell assays. Measurements of glucose uptake and lactate production were done using corresponding kits. Several protein levels were detected by western blotting. The regulation mechanism of circR3HCC1L was verified by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Exosomes were separated by differential ultracentrifugation. Animal experiments were used to verify the function of hypoxia-derived exosomal circR3HCC1L. CircR3HCC1L was upregulated in PAAD samples and hypoxic PAAD cells. Knockdown of circR3HCC1L decreased hypoxia-driven PAAD cell proliferation, migration, invasion, and glycolysis. Hypoxic PAAD cell-derived exosomes had higher levels of circR3HCC1L, hypoxic PAAD cell-derived exosomal circR3HCC1L promoted normoxic cancer cell malignant transformation and glycolysis in vitro and xenograft tumor growth in mouse models in vivo. Mechanistically, circR3HCC1L regulated pyruvate kinase M2 (PKM2) expression via sponging miR-873-5p. Also, PKM2 overexpression or miR-873-5p silencing offset circR3HCC1L knockdown-mediated effects on hypoxia-challenged PAAD cell malignant transformation and glycolysis. Hypoxic PAAD cell-derived exosomal circR3HCC1L facilitated PAAD progression through the miR-873-5p/PKM2 axis, highlighting the contribution of hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD., Competing Interests: Declarations. Ethics Approval: Written informed consents were obtained from all participants and this study was permitted by the Ethics Committee of Ningbo Medical Center Lihuili Hospital., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study explores the bidirectional relation of esophageal squamous cell carcinoma (ESCC) and oral squamous cell carcinoma (OSCC), examining shared risk factors and underlying molecular mechanisms. By employing random forest (RF) classifier, enhanced with interpretable machine learning (IML) through SHapley Additive exPlanations (SHAP), we analyzed gene expression from two GEO datasets (GSE30784 and GSE44021). The GSE30784 dataset comprises 167 OSCC samples and 45 control group, whereas the GSE44021 dataset encompasses 113 ESCC samples and 113 control group. Our analysis led to identification of 20 key genes, such as XBP1, VGLL1, and RAD1, which are significantly associated with development of ESCC and OSCC. Further investigations were conducted using tools like NetworkAnalyst 3.0, Single Cell Portal, and miRNET 2.0, which highlighted complex interactions between these genes and specific miRNA targets including hsa-mir-124-3p and hsa-mir-1-3p. Our model achieved high precision in identifying genes linked to crucial processes like programmed cell death and cancer pathways, suggesting new avenues for diagnosis and treatment. This study confirms the bidirectional relationship between OSCC and ESCC, laying groundwork for targeted therapeutic approaches. This study helps to identify shared biological pathways and genetic factors of these conditions for designing personalized medicine strategies and to improve disease management., Competing Interests: Declarations. Ethical and informed consent for data used: No ethical data was used. Publicly available data is being extracted from the online repository that is the GEO database. Competing interests: The authors declare no competing interests., (© 2024. International Federation for Medical and Biological Engineering.)

Background: Abnormally expressed circular RNAs (circRNAs) are associated with many diseases and have important biological effects on the regulation of gene expression. However, the circRNA expression profile in incomplete radiofrequency ablation (RFA)-treated liver cancer (LC) patients has not been characterized. This study investigated the potential biological effects of differentially expressed (DE) circRNAs in an incomplete RFA-treated transplantation tumor model of human LC., Material/methods: A circRNA microarray was utilized to analyze changes in the circRNA expression profiles. CircRNA host gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also conducted using computational biology. Quantitative real-time PCR (qPCR) was also performed on the selected DE-circRNAs to verify the reliability of the microarray. The circRNA/miRNA interactions were predicted by Arraystar software and confirmed by a dual-luciferase assay., Results: Following RFA incomplete ablation, 76 DE-circRNAs were detected (|fold change |>1.5, P-value < 0.05), 21 of which were upregulated and 55 of which were downregulated. Computational biological analysis revealed that the T-cell receptor signaling pathway was the most significantly enriched pathway of the genes related to altered expression, as indicated by enrichment of LCK, AKT3 and DLG1. PCR results for the upregulated hsa&#95;circRNA&#95;103595 and downregulated hsa&#95;circRNA&#95;001264 indicated that the circRNA microarray sequencing results were reliable. Double luciferase reporter assays confirmed that hsa-miR-185-3p was the target miRNA of hsa&#95;circRNA&#95;103595., Conclusions: The current study confirmed the changes in the expression profiles of circRNAs in tumor transplantation models after incomplete ablation, these changes may play a crucial role in the pathophysiological process of residual cancer transplantation tumors. These findings could lead to new directions for investigating the molecular biological mechanisms underlying RFA-treated LC as well as new ideas for treating LC by regulating circRNAs., Competing Interests: Declarations. Ethics Approval and Consent to Participate: All animal procedures were approved by the animal care and experiment committee of Guangxi Medical University. All experiments were performed in accordance with the experimental animal care and use guidelines of the USA’s National Institutes of Health. This study complies with ARRIVE guidelines ( https://arriveguidelines.org ). Consent for Publication: Not applicable. Conflict of Interest: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intraventricular hemorrhage results in posthemorrhagic hydrocephalus (PHH). Neonatal hydrocephalus remains a challenging disease due to the high failure rate of all management strategies. We evaluated long noncoding RNA growth arrest-specific 5 (GAS5)-mediated network in neonatal hydrocephalus, providing a new direction for the treatment of hydrocephalus. The PHH model was constructed in neonatal rats after intracerebroventricular injection with GAS5, miR-325-3p, and chaperonin containing T-complex protein 1, subunit 8 (CCT8) plasmids, or oligonucleotides. Next, behavioral tests, measurement of serum inflammation, observation of brain tissue pathology, and calculation of hemoglobin and brain water contents were implemented. GAS5, miR-325-3p, and CCT8 expression, in combination with their interactions, was checked. As the results reported, collagenase infusion induced hydrocephalus, impairing neurological function, enhancing inflammation and neuronal apoptosis, and increasing hemoglobin and brain water contents. GAS5 and CCT8 were up-regulated, while miR-325-3p was down-regulated in hydrocephalic rats. Downregulating GAS5/CCT8 or upregulating miR-325-3p could inhibit inflammatory response and improve neurological function in young hydrocephalic rats. GAS5 promotes CCT8 expression through sponge adsorption of miR-325-3p. GAS5 silencing-mediated protections against hydrocephalus were counteracted by CCT8 overexpression. In summary, GAS5 aggravates neonatal hydrocephalus and inflammatory responses in a way of leasing miR-325-3p-involved regulation of CCT8., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest to declare. Ethical Approval: All animal experiments were complied with the ARRIVE guidelines and performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The experiments were approved by the Institutional Animal Care and Use Committee of Chongqing Medical University (Approval Number: 201706-AC59311)., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Circular RNAs (circRNAs) exert critical functions in colorectal cancer development. In this work, we wanted to elucidate the functional role and regulatory mechanism of circ&#95;0007351 in colorectal cancer. For quantification of circ&#95;0007351, microRNA (miR)-5195-3p and G Protein-coupled receptor class C group 5 member A (GPRC5A), a qRT-PCR, immunoblotting or immunohistochemistry assay was performed. Effects of circ&#95;0007351/miR-5195-3p/GPRC5A cascade were evaluated by determining cell viability, proliferation, colony formation, motility, and invasion. Relationships among variables were assessed by dual-luciferase reporter assay. Animal studies were performed to evaluate circ&#95;0007351's function in the growth of xenograft tumors. Circ&#95;0007351 was markedly up-regulated in colorectal cancer tissues and cells. Down-regulation of circ&#95;0007351 hindered cell growth, migration and invasiveness. Also, circ&#95;0007351 depletion exerted a suppressive function in colorectal cell xenograft growth in vivo. Mechanistically, circ&#95;0007351 sponged miR-5195-3p to sequester miR-5195-3p. Reduction of available miR-5195-3p neutralized the effects of circ&#95;0007351 down-regulation on cell phenotypes. MiR-5195-3p directly targeted and inhibited GPRC5A. Circ&#95;0007351 regulated GPRC5A expression by sponging miR-5195-3p. Moreover, the effects of circ&#95;0007351 down-regulation on cell functional phenotypes were due to in part the reduction of GPRC5A expression. Our findings show that circ&#95;0007351 down-regulation impedes proliferation, motility, and invasiveness in colorectal cancer cells at least in part via the regulation of the miR-5195-3p/GPRC5A cascade, highlighting that circ&#95;0007351 inhibition may have a potential therapeutic value for colorectal cancer., Competing Interests: Declarations. Conflicts of interest: The authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Non-alcoholic fatty liver disease (NAFLD) is a disease with various levels varying from fatty liver steatosis to acute steatosis which is non-alcoholic steatohepatitis (NASH), which can develop into hepatic failure, as well as in some conditions it can develop into hepatocellular carcinoma (HCC). In the NAFLD and NASH context, aberrant microRNA (miRNA) expression has a thorough contribution to the incidence and development of these liver disorders by influencing key biological actions, involving lipid metabolism, inflammation, and fibrosis. Dysregulated miRNAs can disrupt the balance between lipid accumulation and clearance, exacerbate inflammatory responses, and promote fibrogenesis, thus advancing the severeness of the disorder from simple steatosis to more complex NASH. In the current review, the latest development concerned with the activity of complex regulatory networks of miRNA in the incidence as well as the evolution of NAFLD is to be discussed, also conferring about the miRNAs' role in the onset, pathogenesis as well as diagnosis of NAFLD and NASH discussing miRNAs' role as diagnostic biomarkers and their therapeutic effects on NAFLD/NASH., Competing Interests: Declarations. Ethics approval and consent to participate: Not Applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: The author declares they have no conflict of interest. Human and animal ethics: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Key Message: A high-throughput sequencing identified 1283 lncRNAs in anthers at different stages in Arabidopsis and their relationship with protein-coding genes and miRNAs during anther and pollen development were analyzed. Long non-coding RNAs (lncRNAs) are important regulatory molecules involved in various biological processes. However, their roles in male reproductive development and interactions with miRNAs remained elusive. In this study, a high-throughput sequencing of anthers at different developmental stages in Arabidopsis identified 1283 lncRNAs including 524 differentially expressed lncRNAs (DELs). Most of these DELs exhibited positive correlations with the expression patterns of adjacent protein-coding genes. Weighted gene co-expression network analysis (WGCNA) revealed that protein-coding genes targeted by DELs in four modules related to the tetrad stage were associated with functions such as pollen wall formation, pollen germination, or pollen tube growth, respectively. Furthermore, five, 10, and 11 lncRNAs were predicted as miRNAs' endogenous target mimics (eTMs), precursors, and natural antisense transcripts of pri-miRNA, respectively. Remarkably, the lncRNA, host gene of ath-miR167a (ath-miR167aHG), predicted as the precursor of miR167a, was selected for function validation. Its overexpression resulted in the up-regulation of miR167a and the subsequent down-regulation of miR167a's target genes ARF6 and ARF8, demonstrating a functional interaction between ath-miR167aHG and miR167a. The transgenic plants showed delayed flowering, shorter filaments, abnormal anther dehiscence, and undeveloped siliques ultimately, suggesting a role of ath-miR167aHG in male reproductive development. Collectively, our research shed new light on the functions of lncRNAs in male reproductive development and uncovered the unique interactions between lncRNAs and miRNAs., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest associated with this work., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fish disease outbreaks caused by bacterial burdens are responsible for decreasing productivity in aquaculture. Unraveling the molecular mechanisms activated in the gonads after infections is pivotal for enhancing husbandry techniques in fish farms, ensuring disease management, and selecting the most resilience phenotype. The present study, with an important commercial species the European sea bass (Dicentrarchus labrax), an important commercial species in Europe, examined changes in the miRNome and transcriptome 48 h after an intraperitoneal infection with Vibrio anguillarum. The findings indicate that following infection, testes exhibited more pronounced alterations in both the miRNome and transcriptome. Specifically, males showed approximately 26% more differentially expressed genes in testicular genes compared to females (2,624 vs. 101 DEGs). Additionally, four miRNAs (miR-183-5p, miR-191-3p, miR-451-5p, and miR-724-5p) were significantly expressed post-infection in males, while none were identified in females. Interestingly, upon deep analysis of sexual dimorphic gene modules, a larger number of miRNAs were identified in infected females targeting genes related to the immune system compared to infected males. These results suggest that fish ovaries demonstrate greater resilience in response to infections by suppressing genes related to the immune system through a post-transcriptional mechanism performed by miRNAs. In contrast, testes activate genes related to the immune system and repress genes related to cellular processes to cope with the infection. In particular, the crosstalk between the miRNome and transcriptome in infected males revealed a pivotal gene, namely, insulin-like growth factor binding protein (igfbp), acting as a gene network hub in which miR-192-3p was connected. The current study elucidated the need to comprehend the basic immune regulatory responses associated with miRNAs and gene regulation networks that depend on fish sex. The data reveal the importance of considering sex as a factor in interpreting the immune system in fish to generate efficient protocols to prevent outbreaks in fish farms., Competing Interests: Declarations. Ethics approval and consent to participate: European sea bass experiments were performed in well-equipped fish facilities at the Institute of Agrifood Research and Technology (IRTA, la Ràpita, Tarragona, Spain, https://www.irta.cat/es/produccion-animal/acuicultura ). All animal procedures included in this project were conducted in compliance with an experimental research protocol approved by the committee of ethics and animal experimentation of the IRTA and the Catalan Government (project n° 12197, file n° FUE-2023-03496883 and ID SLNBB6432) based on Real Decreto 53/2013 and in accordance with the guidelines of the European Union Council (2010/63/EC) for the use of laboratory animals. IRTA is an authorized biosecurity facility to work with pathogens (NBS2) certified by registers numbers: EA-01/17 and IRTA-SCRT9900002 approved by Animal Protection Section (Catalan Government). Present animal research adheres to the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines. Consent for publication: All author consent the publication of the current article. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

One of the outstanding features of chronic hepatitis B infection (CHB) is its strong association with liver fibrosis. CHB induced inflammation and injury trigger multiple biochemical and physical changes that include the promotion of a wide range of cytokines, chemokines and growth factors that activate hepatic stellate cells (HSCs) CHB induced activation of hepatic stellate cells (HSCs) is regarded as a central event in fibrogenesis to directly promote the synthesis of myofibroblasts and the expression of a range of materials to repair injured liver tissue. Fibrogenesis is modulated by the mainstream epigenetic machinery, as well as by non-coding RNA (ncRNA) that are often referred to as an ancillary epigenetic response to fine tune gene expression. Although extensive research has explained the regulatory role of ncRNA in liver fibrogenesis, most of this research relates to non-CHB etiologies. This review paper outlines the complex interactive regulatory role of microRNA (miRNA) and their interaction with long non-coding RNA (lncRNA), circular RNA (circRNA) and the mainstream epigenetic machinery in CHB induced liver fibrosis. The paper also illustrates some of the difficulties involved in translating candidate ncRNA into approved drugs or diagnostic tools. In conclusion, the important regulatory role of ncRNA in CHB induced liver fibrosis warrants further investigation to exploit their undoubted potential as diagnostic and therapeutic agents., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Advancements in bioinformatic tools and breakthroughs in high throughput RNA sequencing have unveiled the potential role of non-coding RNAs in influencing the overall expression of disease-responsive genes. Owing to the increasing need to develop resilient crop varieties against environmental constraints, our study explores the functional relationship of various non-coding RNAs in wheat during leaf rust pathogenesis. MicroRNAs (miRNAs) and circular RNAs (circRNAs) were retrieved from SAGE and RNA-Seq libraries, respectively, in the susceptible (HD2329) and resistant (HD2329 + Lr28) wheat Near-Isogenic Lines (NILs). Here we explored the previously published circRNAs for their differential expression and correlated the data with the differentially expressed miRNAs (DEMs) through various in silico methods to acquire the target miRNAs of circRNAs and the downstream target mRNAs of miRNAs. Finally, a competing endogenous RNA (ceRNAs) regulatory network was constructed and validated through RT-qPCR method. We have identified the ceRNA regulatory network of four differentially expressed circRNAs (DECs) and five DEMs to highlight their crucial roles in the robust enhancement of the temporal expression profiles of five defense responsive genes (mRNAs) in wheat NILs against leaf rust infection. The study confirms the synergistic expression of circRNAs and mRNAs with an antagonistic correlation with the expression profile of the corresponding miRNAs. The vital role of leaf rust-resistant gene Lr28 has also been highlighted for driving the efficiency of the circRNAs to upregulate target gene expression. Thus, understanding the circRNA-miRNA-target gene interaction during leaf rust pathogenesis can help to identify stress-specific regulatory biomarkers to enhance defense responses in wheat for improved resilience through multi-omics integration of transcriptomics, proteomics and metabolomics., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sitobion miscanthi is a wheat aphid species that can damage seriously agricultural production. The effective management of wheat aphids has depended on chemical insecticides. However, their wide application led to severe resistance of wheat aphids to some insecticides, and cytochrome P450 as a detoxifying enzyme plays a crucial role in the insecticide resistance. In this study, CYP6CY1, a new P450 gene, was isolated and overexpressed in a S.miscanthi resistant strain to imidacloprid. The increased sensitivity to imidacloprid after silencing of CYP6CY1 indicated that its involvement in imidacloprid resistance. Subsequently, action of miR-3047-3p within the 3' UTR of the CYP6CY1 was confirmed at the posttranscriptional regulatory level, and was shown to be involved in the resistance to imidacloprid. These results provide opportunities for understanding the roles of P450 in insecticide resistance of pests., Competing Interests: Declarations. Conflict of Interest: The authors declare no competing interests., (© 2025. Sociedade Entomológica do Brasil.)

Alzheimer's disease (AD) is a neurodegenerative disease that primarily affects the elderly population and is the leading cause of dementia. Meanwhile, the vascular hypothesis suggests that vascular damage occurs in the early stages of the disease, leading to neurodegeneration and hindered waste clearance, which in turn triggers a series of events including the accumulation of amyloid plaques and Tau protein tangles. Non-coding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), have been found to be involved in the regulation of AD. Furthermore, lncRNAs and circRNAs can act as competitive endogenous RNAs to inhibit miRNAs, and their interactions can form a complex regulatory network. Exosomes, which are extracellular vesicles (EVs), are believed to be able to transfer ncRNAs between cells, thus playing a regulatory role in the brain by crossing the blood-brain barrier (BBB). Exosomes are part of the intercellular carrier system; therefore, utilizing exosomes to deliver drugs to recipient cells might not activate the immune system, making it a potential strategy to treat central nervous system diseases. In this review, we review that AD is a multifactorial neurological disease and that ncRNAs can regulate its multiple pathogenic mechanisms to improve our understanding of the etiology of AD and to simultaneously regulate multiple pathogenic mechanisms of AD through the binding of ncRNAs to exosomes to improve the treatment of AD., Competing Interests: Declarations. Ethics approval: Not applicable. Informed consent: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Imatinib resistance is a major obstacle to the successful treatment of gastrointestinal stromal tumors (GIST). Long non-coding RNAs (LncRNAs) have been identified as important regulatory factors in chemotherapy resistance. This study aimed to identify key lncRNAs involved in imatinib resistance of GISTs. First, MSC-AS1 was found to be upregulated in imatinib-resistant GIST tissues and imatinib-resistant GIST cells. Cellular experiments demonstrated that MSC-AS1 overexpression decreased imatinib sensitivity of GIST cells, evidenced by increased cell survival, colony formation, migration, and invasion. Moreover, suppression of MSC-AS1 improved the imatinib resistance of imatinib-resistant GIST cells. Furthermore, MSC-AS1 upregulated the expression of FNDC1 and Anillin via sponging miR-200b-3p, activated the phosphatidylinositol-3-kinase-AKT signaling pathway, and thereby driving imatinib resistance in vitro and in vivo. Overall, this study elucidates the crucial role and mechanism of MSC-AS1 in the imatinib resistance of GIST, providing the potential therapeutic strategy for overcoming the imatinib resistance of GIST., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All clinical experiments were approved by the Ethics Committee at China-Japan Union Hospital of Jilin University (2023-KYYS-023) and operated following the Declaration of Helsinki. Informed consent: Informed consent was obtained from all participants. Human or animal rights: All animal experiments were conducted in accordance with institutional guidelines and were approved by the Institutional Animal Care and Use Committee of Yishengyuan Gene Technology Co., LTD (No. 20240107)., (© 2025. The Author(s) under exclusive licence to Japan Human Cell Society.)

Breast cancer, a prevalent and aggressive malignancy among females worldwide, poses a significant challenge due to resistance to chemotherapy and tyrosine kinase inhibitors. In breast cancer, ABC transporters play a pivotal role by contributing to chemoresistance and drug efflux, a phenomenon observed also in various cancers. This study aims to elucidate the role of oncomiRs miR-15, miR-21, and miR-let-7 in breast cancer etiology and their impact on chemotherapy-resistant oncogenes ABCA1, ABCB1, and ABCC1. Blood samples from female breast cancer patients were analyzed to assess the expression levels of miRNAs and oncogenes by qPCR. Significantly, miR-21 exhibited a positive correlation with ABCA1 in newly diagnosed patients, while miR-15 and miR-let-7 displayed a positive correlation with ABCA1 in the metastasis group. Additionally, miR-let-7 demonstrated a negative correlation with ABCC1 in newly diagnosed patients. This study's findings provide valuable insights into the cancer etiology of these miRNAs and their interactions with ABCA1, ABCB1, and ABCC1. Targeting these interactions holds promise for mitigating drug efflux and chemoresistance in breast cancer, potentially enhancing current treatments and improving patient outcomes., Competing Interests: Declarations. Conflict of interests: The authors state that they do not have any competing interests. Participant Consent and Ethical Approval: All Data were collected under supervision of Co-author Dr. Mohammed A. Suwaid, also the work approved by University of Anbar and Anbar Health office with approval no. MOH-BC-312MA. Publication Consent: The authors have no objection to publishing this work., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Plant and fungus interaction is a complex process involving many molecular factors determining the nature of relationship. The enigmatic methodology by which fungal endophytes are able to colonise a plant harmoniously is still inexplicable. Small RNAs have been identified as major regulatory elements under various biotic interactions. However, their role in endophytic plant-fungal interactions remain to be elucidated. Therefore, transcript expression data available on Gene Expression Omnibus for Arabidopsis thaliana was utilised for miRNAs identification under endophytism. The analysis predicted 15 miRNAs with differential expression of which the ath-miRNA398b modulation was significant. Application of psRNAtarget, C-mii, pmiREN, and TarDB provided a pool of 357 target genes for these miRNAs. Protein-protein interaction analysis identified major hub proteins, including BTB/POZ domain-containing protein, beta-Xylosidase-2 (AtBXL2), and Copper/Zinc Superoxide Dismutase-2 (AtSOD2). The quantitative real-time PCR validated the computational prediction and expression for selected target genes AtSOD2, AtBXL2, and AtRCA along with ath-miRNA398b under endophytism. Overall, results indicate that miRNAs have a significant role in regulating Arabidopsis thaliana-endophytic fungal interaction., Competing Interests: Declarations. Conflict of interest: The authors declare that they do not have conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The newly discovered LINC02532 is abnormally expressed in a variety of cancers and promotes cancer progression. The research proposed to discover the biological and molecular mechanisms of LINC02532 in breast cancer (BCa). In the resected BCa tissue samples and adjacent normal tissues, LINC02532, miR-541-3p, and High Mobility Group A1 (HMGA1) levels were determined. Cell function experiments were carried out on the premise of cell transfection with relevant plasmids. Based on that, the influence of LINC02532, miR-541-3p, and HMGA1 on MCF-7 cell activities (proliferation, migration, invasion, cell cycle, and apoptosis) was determined, as well as on EMT. Additionally, animal experiments were allowed to support cell experimental conclusions on LINC02532. Finally, the mechanistic network of LINC02532, miR-541-3p, and HMGA1 was identified. It was BCa tissues highly expressing LINC02532 and HMGA1, while lowly expressing miR-541-3p. Functionally, LINC02532 depletion repressed the activities and EMT process of MCF-7 cells. Silencing LINC02532 delayed tumor growth in mice. In terms of mechanism, LINC02532 mainly existed in the cytoplasm and could mediate HMGA1 expression by absorbing miR-541-3p. The findings offer new insights into the molecular mechanisms of LINC02532 in BCa and, more importantly, new strategies for the clinical treatment of BCa., Competing Interests: Declarations. Conflict of interests: Authors declared no conflict of interest. Ethical Approval: All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All subjects was approved by Shandong Provincial Hospital Affiliated to Shandong First Medical University. And The animal experiment research protocol was approved by the Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong First Medical University and performed in accordance with the “Guidelines for the care and use of experimental animals.”, (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Osteoarthritis (OA) is the most common joint disease worldwide, with an age-associated increasing in both incidence and prevalence. However, early diagnosis of OA is a challenge due to the lack of effective biomarkers. This study aimed to identify new biomarkers and mechanisms of OA., Methods: Microarray expression data of synovial tissues from osteoarthritic and healthy populations were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified using GEO2R. Functions and enrichment pathways of DEGs were explained by enrichment analysis and construction of protein-protein interaction (PPI) networks, and hub genes were identified., Results: By performing Venn analysis on the DEGs obtained from the two datasets, 28 upregulated and 84 downregulated DEGs were gained. JUN, activating transcription factor 3 (ATF3), and Dual-specificity phosphatase 1 (DUSP1), which play important roles in OA, were screened using PPI network construction. The receiver operating characteristic (ROC) curve of JUN, ATF3, and DUSP1 revealed satisfactory diagnostic value for OA. hsa-mir-26b-5p interacts with JUN, ATF3, and DUSP1., Conclusion: The expression of JUN, ATF3, and DUSP1 was reduced in patients with OA and the three genes mentioned above could be used as potential markers for the diagnosis of OA. hsa-mir-26b-5p may play an important role in the pathogenesis of OA and may be a potential therapeutic target. Key Points • JUN, ATF3, and DUSP1 could be used as potential markers for the diagnosis of OA. • hsa-mir-26b-5p may play an important role in the pathogenesis of OA., Competing Interests: Compliance with ethical standards. Ethics statement: Our study did not require an ethical board approval because it did not contain human or animal trials. Consent for publication: Not applicable. Disclosures: None., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Acute respiratory distress syndrome is a disease triggered by severe pulmonary and systemic inflammation that may lead to fibrosis and the decline of lung function. Lung capillary endothelial-to-mesenchymal transition (EndMT) is one of the primary sources of fibroblasts in pulmonary fibrosis. The role of miRNAs as molecular markers of pulmonary fibrosis, and miRNAs as nucleic acid drugs has attracted increasing attention. To mock EndMT process, Human pulmonary microvascular endothelial cells (HPMECs) were induced with lipopolysaccharide (LPS). Similarly, LPS treatment was used to generate a mouse model of LPS-induced EndMT and pulmonary fibrosis. LPS-induced EndMT in HPMECs resulted in a significant reduction of miR-23b-3p. miR-23b-3p inhibited the interstitial transition of HPMECs, and miR-23b-3p could mediate this process via inhibiting dipeptidyl peptidase-4 (DPP4). Dual-luciferase assays confirmed the regulatory mechanism of miR-23b-3p. In our mouse model of LPS-induced pulmonary fibrosis, miR-23b-3p and a DPP4 inhibitor (sitagliptin) individually alleviated LPS-induced EndMT progression and pulmonary fibrosis, and their combined use achieved the strongest remission effect. To sum up, miR-23b-3p alleviates EndMT in pulmonary fibrosis by inhibiting the expression of DPP4., Competing Interests: Declarations. Competing Interests: The authors declare that they have no competing interests., (© 2023. The Author(s).)

Neonatal hypoxic-ischemic encephalopathy (HIE) is a critical condition resulting from impaired oxygen and blood flow to the brain during birth, leading to neuroinflammation, neuronal apoptosis, and long-term neurological deficits. Despite the use of therapeutic hypothermia, current treatments remain inadequate in fully preventing brain damage. Recent advances in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer a novel, cell-free therapeutic approach, as these EVs can cross the blood-brain barrier (BBB) and deliver functional microRNAs (miRNAs) to modulate key pathways involved in inflammation and neuroprotection. This review examines how specific miRNAs encapsulated in MSC-EVs-including miR-21, miR-124, miR-146, and the miR-17-92 cluster-target the complex inflammatory responses that drive HIE pathology. By modulating pathways such as NF-κB, STAT3, and PI3K/Akt, these miRNAs influence neuroinflammatory processes, reduce neuronal apoptosis, and promote tissue repair. The aim is to assess the therapeutic potential of miRNA-loaded MSC-EVs in mitigating inflammation and neuronal damage, thus addressing the limitations of current therapies like therapeutic hypothermia., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable. Competing Interests: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diffuse large B-cell lymphoma (DLBCL) is the leading cause of mortality from invasive hematological malignancies worldwide. MicroRNA-7-5p (miR-7-5p) has been shown to be a tumor suppressor in several types of tumors. However, its role in DLBCL is not fully understood. This study explored the role of miR-7-5p in the progression of DLBCL and pursued the underlying mechanism. Quantitative real-time PCR and transfection of miRNA mimic and inhibitors were used to assess the effects of miR-7-5p on autophagy and apoptosis in SU-DHL-4 and SU-DHL-10 cells. Dual-luciferase reporter assay was used to identify target genes of miR-7-5p. Immunofluorescence, flow cytometry, and western blotting (WB) were performed to explore the underlying mechanism and downstream pathways of miR-7-5p and AMBRA1 in DLBCL cells. MiR-7-5p was upregulated in DLBCL cells. Luciferase reporter assays implicated AMBRA1 as a downstream target of miR-7-5p in DLBCL. WB and flow cytometry showed that an increase in miR-7-5p level and a decrease in AMBRA1 expression led to a decrease in autophagy and apoptosis-related protein expression. Furthermore, miR-7-5p prevented c-MYC dephosphorylation through AMBRA1 downregulation. On the contrary, c-MYC increased the expression of miR-7-5p, thereby establishing positive feedback on miR-7-5p transcription. The addition of hydroxychloroquine, an autophagy inhibitor, reduced autophagy and increased apoptosis in DLBCL cells. In vivo experiments further proved that the increase of miR-7-5p played a regulatory role in the expression of downstream AMBRA1 and c-MYC. These results demonstrate that c-MYC-dependent MiR-7-5p suppressed autophagy and apoptosis by targeting AMBRA1 in DLBCL cells. MiR-7-5p also suppressed autophagy and apoptosis by targeting AMBRA1 in DLBCL cells. Therefore, these data suggest that targeting miR-7-5p may be a promising strategy in DLBCL therapy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: All animal experimental protocols were reviewed and verified by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The Experimental Animal Ethics Committee of The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine reviewed and verified all animal experimental protocols in accordance with the Guidelines for Ethical Review of Experimental Animals of Guangzhou University of Traditional Chinese Medicine. (No. TCMF1-2021017). Consent for publication: All authors consent to the publication of this article., (© 2024. The Author(s).)

Recurrent spontaneous abortions (RSA) is defined as a loss of two or more consecutive clinically recognized pregnancies before the 20th week of gestation. In RSA, several causative maternal factors are known, but still, 50% of the cases remain unexplained. Evidence suggests that paternal factors are also equally important. Epigenetic phenomenon such as genomic imprinting and regulation of gene expression by miRNAs plays an important role in embryonic and placental development. Two large miRNA clusters, C14MC (Chromosome 14 microRNA cluster) and C19MC (Chromosome 19 microRNA cluster) are imprinted and expressed in the placenta during pregnancy and are known to regulate functionally important processes such as the trophoblast proliferation, adhesion, and migration. Hence, we studied the DNA methylation at the Differentially Methylated Regions (DMRs) of these clusters in spermatozoa and chorionic villi by pyrosequencing. In Spermatozoa, few Cytosine followed by Guanosine (CpG) sites at DMRs of C14MC and C19MC showed significant hypermethylation. In Chorionic villi, CpG sites showed significant hypomethylation in the RSA group as compared to control group. Semen parameters like sperm concentration, sperm motility, morphology, and chromatin compaction were comparable in control and RSA groups. The study suggests aberrant DNA methylation in spermatozoa and chorionic villi at DMRs of both miRNA coding clusters to be associated with RSA., Competing Interests: Declarations. Ethical Approval: The study was approved by the Institutional Ethics Committee for Clinical Studies (National Institute for Research in Reproductive and Child Health); 332/2018. Conflict Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

More and more articles have shown that non-coding RNAs (ncRNAs) play a significant role in the pathogenesis and prognosis of ischemic stroke. However, the bibliometric analysis in ncRNAs and ischemic stroke is still lacking. This study retrieved the Web of Science Core Collection for relevant articles from January 1, 2010 to April 6, 2023. Bibliometrix R, VOSviewer, and CiteSpace were used to perform the bibliometric analysis. A total of 1058 articles were eligible for this review. The number of publications showed a fluctuating upward trend. The total citations were 28,698 times, and the average number of citations per article was 27.12 times. Our findings indicated ncRNAs has been increasingly investigated for its critical role in apoptosis, autophagy, angiogenesis, inflammation, oxidative stress, and blood-brain barrier after ischemic stroke by regulating target mRNAs, extracellular secretion, target proteins, and others. The microRNAs, circular RNAs, and long ncRNAs may be hotspots, and ferroptosis, METTL3, and exosome might be frontier in this field. Besides, ncRNAs have a promising future as diagnostic and prognostic biomarkers, molecular drug targets, and other targeted therapies for ischemic stroke. However, it still faces many challenges to be successfully applied in the clinical practice., Competing Interests: Declarations. Conflict of Interests: The authors declare no conflict of interest. Ethics Approval and Consent to Participate: Not applicable., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

MicroRNAs (miRNAs) are typically non-coding RNAs of 18-26 nucleotides (nts) that are produced endogenously and regulated post-transcriptionally through degradation or translational repression. Since miRNAs are evolutionarily conserved, their preservation is essential for important regulatory functions in plant development, growth, and responses to environmental stress. Sorghum bicolor (sbi) is a valuable food and fodder crop which is grown worldwide. A range of sbi miRNAs were identified so far as being connected to plant development and stress responses. Herein, we employed a variety of bioinformatics tools for miRNA profiling in sbi and a PCR-based platform for the validation of these miRNAs. In total, 74 new conserved sbi miRNAs from 52 miRNA families have been predicted. Using the psRNA Target method, 10613 different protein targets of these predicted miRNAs have been attained. These targets include 54 GO-terms which have substantial targets in the biological, molecular, and cellular processes. We particularly found that the sbi-miR1861c and sbi-miR5050 are involved to regulate sulphur compound biosynthetic process, while the significant spliceosomal complex is regulated by sbi-miR815b and sbi-miR7768b. Also, we report that the pre-ribosome, electron transport chain, cell communication, cellular respiration, protein localization, and photosynthesis are controlled by sbi-miR2907b, sbi-miR530, sbi-miR7749, sbi-miR1858a, sbi-mi7729a, and sbi-miR417, respectively. The identification and validation of these novel sbi miRNAs shall contribute a lot in improving the crop yield and ensure sustainable agriculture., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Ethical approval: Not Applicable., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sorafenib (SOR) is the first-line chemotherapeutic therapy for hepatocellular carcinoma (HCC) treatment, but SOR resistance is a key factor affecting the therapeutic effect. Emerging studies have suggested that circular RNAs (circRNAs) play an important role in the development of drug resistance in HCC cells. This paper aimed to elucidate the potential role and molecular mechanism of circRNA Scm polycomb group protein homolog 1 (circSCMH1) in SOR-resistant HCC cells. CircSCMH1, microRNA-485-5p (miR-485-5p), and hematological and neurological expressed 1 (HN1) contents were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8) assay was adopted to detect the SOR sensitivity of cells. Cell proliferation, migration, invasion, and apoptosis were assessed using colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), transwell, and flow cytometry assays. Glucose metabolism was analyzed using commercial kits. HN1, B cell lymphoma-2 (Bcl-2), and Bcl-2-associated X (Bax) protein levels were assessed using western blot. Binding between miR-485-5p and circSCMH1 or HN1 was verified using a dual-luciferase reporter. Xenograft tumor model was used to explore the function of circSCMH1 in vivo. CircSCMH1 expression and HN1 abundances were increased, but the miR-485-5p level was reduced in SOR-resistant HCC tissues and cells. Deficiency of circSCMH1 enhanced SOR sensitivity by suppressing cell proliferation, migration, invasion, and glucose metabolism and inducing cell apoptosis in SOR-resistant HCC cell lines (Huh7/SOR and Hep3B/SOR). Mechanistically, circSCMH1 sponged miR-485-5p to positively regulate HN1 expression. Importantly, circSCMH1 depletion inhibited tumor growth and increased SOR sensitivity in vivo. CircSCMH1 promoted SOR resistance in HCC cells at least partly through upregulating HN1 expression by sponging miR-485-5p. These findings elucidated a new regulatory pathway of chemo-resistance in SOR-resistant HCC cells and provided a possible circRNA-targeted therapy for HCC., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval: The present study was approved by the ethical review committee of The First Affiliated Hospital of Shenzhen University Health Science Center. Written informed consent was obtained from all enrolled patients. Consent for publication: Patients agree to participate in this work., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Triple-negative breast cancer (TNBC) is the most lethal subtype of BC, with unfavorable treatment outcomes. Evidence suggests the engagement of lncRNA MCM3AP-AS1 in BC development. This study investigated the action of MCM3AP-AS1 in chemoresistance of TNBC cells. Drug-resistant TNBC cell lines SUM159PT R and MDA-MB-231 R were constructed by exposure to increasing concentrations of doxorubicin/docetaxel (DOX/DXL). MCM3AP-AS1 and miR-524-5p expression levels were determined by RT-qPCR. RNA binding motif 39 (RBM39) level was measured using Western blot. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The targeted binding of miR-524-5p with MCM3AP-AS1 or RBM39 was predicted by ECORI database and validated by dual-luciferase assays. The gain-and-loss of function assays were conducted in cells to investigate the interactions among MCM3AP-AS1, miR-524-5p, and RBM39. TNBC xenograft mouse models were established through subcutaneous injection of MCM3AP-AS1-silencing MDA-MB-231 R cells and intraperitoneally administrated with DOX/DXL to verify the role of MCM3AP-AS1 in vivo. MCM3AP-AS1 was upregulated in drug-resistant TNBC cells, and MCM3AP-AS1 silencing could sensitize drug-resistant TNBC cells to chemotherapeutic drugs by promoting apoptosis. MCM3AP-AS1 targeted miR-524-5p. After DOX/DXL treatment, miR-524-5p inhibition partially reversed the effect of MCM3AP-AS1 silencing on inhibiting chemoresistance and promoting apoptosis of drug-resistant TNBC cells. miR-524-5p targeted RBM39. Silencing MCM3AP-AS1 promoted apoptosis via the miR-524-5p/RBM39 axis, thereby enhancing chemosensitivity of drug-resistant TNBC cells. MCM3AP-AS1 knockdown upregulated miR-524-5p, downregulated RBM39, and restrained tumor development in vivo. MCM3AP-AS1 silencing potentiates apoptosis of drug-resistant TNBC cells by upregulating miR-524-5p and downregulating RBM39, thereby suppressing chemoresistance in TNBC., Competing Interests: Declarations. Competing interest: All authors declare that there is no conflict of interests in this study. Ethical approval: All animal experimental procedures were ratified by the Research Ethics Committee of Anhui Medical University and conducted in strict accordance with the National Guide for Laboratory Animals(Approval number: LLSC20220982). Considerable efforts were made to minimize the animal amount and their suffering. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

MicroRNAs (miRNAs) play a crucial role in gene regulation and the development of keloid. This research aimed to identify and verify miRNAs associated with keloids by microarray analysis and in vitro experiments, shedding light on seeking for potential therapeutic molecular targets. In this study, the weighted gene co-expression network analysis was performed based on the GSE113620. The key miRNA module most relevant to the keloid was further screened to identify hub miRNAs, and then hub miRNAs was verified by the microarray analysis and qRT-PCR experiments. Additionally, targeted genes of hub miRNAs were predicted and verified. Gene ontology (GO) analysis and KEGG enrichment analysis were also conducted. Five miRNA modules were divided, and the blue module exhibited the highest correlation with keloids. Then, hsa-miR-127-3p, hsa-miR-214-3p, hsa-miR-155-5p, hsa-miR-409-5p, and hsa-miR-542-5p were identified as the hub miRNAs. Subsequently, the microarray analysis and qRT-PCR results demonstrated that the expression of five miRNAs were upregulated in keloid tissues. The GO analysis revealed that the target genes of these miRNAs were mainly enriched in biological processes including gene transcription, protein phosphorylation and the MAPK (mitogen-activated protein kinase) cascade, and the KEGG pathway enrichment analysis showed that the PI3K-AKT signaling pathway were significantly enriched. In conclusion, these five miRNAs (hsa-miR-127-3p, hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-409-5p, and hsa-miR-542-5p) play vital roles in the pathogenesis of keloid and might be potential therapeutic targets. These miRNAs might regulate genes enriched in gene transcription, protein phosphorylation, the MAPK cascade, and the PI3K-Akt signaling pathway., Competing Interests: Declarations. Competing interest: None. Ethical Approval: The written informed consent was obtained from all the patients and the study protocol was approved by the Bioethical Committee of Peking Union Medical College Hospital (ZS-2222). Consent for Publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Lung cancer is one of the leading causes of death worldwide. Recent studies have shown that circular RNAs are dysregulated in a variety of cancers, but the mechanism in lung cancer is still indistinct. In our work, we explored the action mechanism of circLDLRAD3 in lung cancer., Methods: The abundance of circLDLRAD3, microRNA-497-5p (miR-497-5p) and platelet-type PFK (PFKP) was measured by real-time quantitative polymerase chain reaction (RT-qPCR) in lung cancer. Meanwhile, the level of PFKP was quantified by western blot. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, wound healing assay, flow cytometry, western blot, immunohistochemical (IHC) assay and glycolysis metabolism analysis were performed for functional analyses. Furthermore, the interplay between miR-497-5p and circLDLRAD3 or FKPF was detected by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Eventually, the in vivo experiments were applied to measure the role of circLDLRAD3., Result: The levels of circLDLRAD3 and PFKP were increased. Silencing circLDLRAD3 inhibited cell viability, proliferation, migration, invasion and glycolysis metabolism and promoted cell apoptosis in lung cancer cells. In mechanism, circLDLRAD3 regulated PFKP level as a miR-497-5p sponge. MiR-497-5p suppressed the progression of lung cancer by inhibiting PFKP. In addition, circLDLRAD3 knockdown also inhibited tumor growth in vivo., Conclusion: CircLDLRAD3 promoted the development of lung cancer through increasing PFKP expression by regulating miR-497-5p, which also provided a potential targeted therapy for lung cancer treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: Maternal western-style diets that are high in glucose and fat have well-known cardiovascular effects on offspring, yet the combined influence of such diets during pregnancy is relatively less comprehended. This study investigates the impact of maternal high glucose and fat diet (HGF) on vascular constriction in offspring and the underlying mechanisms., Methods and Results: Pregnant Sprague-Dawley rats were provided with either HGF or control diets. The assessment of fetal and postnatal vascular function disclosed an enhanced sensitivity to angiotensin II-induced vascular constriction in the offspring exposed to HGF. This was ascribed to increased oxidative stress via upregulated NOX2 expression, which was due to downregulated SHIP2 expression that was influenced by upregulated miR-325-3p. The maternal HGF diet elevated miR-325-3p, suppressed SHIP2 and enhanced NOX2 expression in fetal vascular tissues, thereby resulting in vascular dysfunction. These alterations persist into adulthood, heightening the risk of vascular diseases., Conclusion: The present study is the first to demonstrate that maternal HGF diet impairs vascular constriction function in offspring through the miR-325-3p/SHIP2/NOX2 pathway. These novel findings indicate that the detrimental effects of maternal HGF diet on fetal vascular function can persist into adulthood, advancing our knowledge on the impact of maternal diet on offspring vascular health and the early stages of fetal-origin vascular diseases., Competing Interests: Declarations. Conflict of interests: The authors report there are no competing interests to declare. Ethical approval: Animal experiments are approved and supervised by the Experimental Animal Ethics Committee of Suzhou University. All experiments conformed to international guidelines on the ethical use of animals. Consent to participate: Not applicable. Consent for publication: All authors consent to the publication of the article., (© 2024. The Author(s).)

This study aimed to investigate the mechanism of Xuanhong Dingchuan Tang (XHDCT) in delaying bronchial asthma inflammation via the microRNA (miR)-107-3p/prostaglandin endoperoxide synthase 2 (PTGS2)/mitogen-activated protein kinase (MAPK) axis. Based on the network pharmacological analysis, XHDCT chemical constituents and targets of each chemical constituent were screened through the TCMSP database, and differential-expressed genes of bronchial asthma were obtained from the GEO database, which were intersected to get XHDCT potential anti-inflammatory targets. The key anti-inflammatory targets of XHDCT were acquired by protein-protein interaction (PPI) analysis of the candidate targets. Bronchial asthma mouse models were established and the pathological changes of lung tissues were observed. Serum IgE levels were tested. Total cells and eosinophils in bronchoalveolar lavage fluid (BALF) were counted. The expression of Th2-associated cytokines (interleukin (IL)-4, IL-5, and IL-13) and chemokines (monocyte chemoattractant protein-1 (MCP-1) and eotaxin) in BALF were measured. The targeting relationship between miR-107-3p and PTGS2 was tested. XHDCT delayed bronchial asthma inflammation in in-vivo asthma mouse models. A total of 155 active ingredients and their 341 targets were intersected with bronchial asthma-relevant genes, obtaining 20 potential targets of XHDCT for bronchial asthma treatment. Based on the PPI and "drug-component-target" network diagram, PTGS2 was found to be in a central position. PTGS2 was downregulated and miR-107-3p was upregulated in bronchial asthma mice after XHDCT treatment. PTGS2 overexpression activated the MAPK signaling pathway to promote inflammation in bronchial asthma mice, whereas inflammatory symptoms were reduced and the MAPK signaling pathway was inhibited after XHDCT treatment. miR-107-3p was an upstream regulatory miRNA for PTGS2. After miR-107-3p interference, the activation of the PTGS2/MAPK axis promoted inflammation in bronchial asthma mice, whereas the inflammatory symptoms were reduced after XHDCT treatment. XHDCT promotes anti-inflammatory effects in bronchial asthma via the miR-107-3p/PTGS2/MAPK axis., Competing Interests: Declarations. Ethics approval and consent to participate: The animal care procedures and animal experiments in the research were conducted under the ratification of the Animal Ethics Committee of The First Hospital Affiliated Yunnan University of Chinese Medicine (approval number: 20211107). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Asthma is a chronic inflammatory respiratory disease characterized by recurrent breathing difficulties caused by airway obstruction and hypersensitivity. Although there is diversity in their specific mechanisms, microRNAs (miRNAs) have a significant impact on the development of asthma. Currently, the contribution of miR-130b-3p to asthma remains elusive. The goal of this study was to examine whether miR-130b-3p attenuates house dust mite (HDM)-induced asthma through High-mobility group box protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/mitochondrial fission protein (DRP1) signaling pathway. We elucidate that miR-130b-3p can bind to the HMGB1 3'UTR, attenuating HMGB1 mRNA and protein levels, and nucleo-cytoplasmic translocation of HMGB1. We observed that miR-130b-3p agomir or HMGB1 CKO attenuated HDM-induced airway inflammation and hyperresponsiveness, and decreased Th2-type cytokines in bronchoalveolar lavage fluid (BALF) and mediastinal lymph nodes. Further, HMGB1 CKO contributes to alleviating Th2 inflammation in AT-II cells (CD45.2 - /CD31 - /Epcam -+ /proSP-C + /MHC-II + ) from lung single cell suspensions of asthmatic mice by flow cytometry. Our findings identified miR-130b-3p as a potent regulator in asthma that exerts its anti-inflammatory effects by targeting HMGB1 and the subsequent HMGB1/TLR4/DRP1axis, presenting a prospective novel therapeutic avenue for asthma management., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval: This study did not involve human subjects. The animal experimental were approved by the Animal Experimental Center of Yanbian University ([JI] 2020-00093)., (© 2024. The Author(s).)

Chemotherapy is essential for treating malignant tumors, but it can cause premature ovarian insufficiency (POI). Recent studies suggest that exosomes enriched with miR-21 (miR-21-Exo) may help mitigate POI, though the underlying mechanisms remain largely unexplored. This research investigates how miR-21-Exo influences chemotherapy-induced POI using an experimental model where KGN cells are exposed to cisplatin. We assessed the impact of miR-21 on cellular activity and generated miR-21 overexpressing bone marrow mesenchymal stem cells (miR-21-BMSC) via lentiviral modification. Isolated miR-21-Exo was analyzed for its effects on cellular function. Bioinformatics identified Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT1) as a target of miR-21. We confirmed that miR-21-Exo regulates MALT1 and the NF-κB signaling pathway to prevent cell pyroptosis. Further studies in a rat model demonstrated the therapeutic potential and safety of miR-21-Exo. Overall, our findings highlight a novel strategy for addressing chemotherapy-induced POI by modulating MALT1 and the NF-κB pathway, offering significant therapeutic implications., Competing Interests: Declarations. Ethics approval and informed consent: All animal experiments conducted was compliant with the Ethics Committee of Southern Medical University Zhujiang Hospital (Nọ: LAEC-2022–208). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Central nervous system diseases include central nervous system injury diseases, neurodegenerative diseases, and other conditions. MicroRNAs (miRNAs) are important regulators of gene expression, with therapeutic potential in modulating genes, pathways, and cells associated with central nervous system injury diseases. This article comprehensively reviews the therapeutic role of exosomal miRNAs in various central nervous system injury diseases, including traumatic brain injury, ischemic stroke, intracerebral hemorrhage, optic nerve injury, and spinal cord injury. This review covers the pathophysiology, animal models, miRNA transfection, administration methods, behavioral tests for evaluating treatment efficacy, and the mechanisms of action of miRNA-based therapies. Finally, this article discusses the future directions of miRNA therapy for central nervous system injury diseases., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

The neuroendocrine-immune (NEI) network is fundamental for maintaining body's homeostasis and health. While the roles of microRNAs (miRNAs) and transcription factors (TFs) in disease processes are well-established, their synergistic regulation within the NEI network has yet to be elucidated. In this study, we constructed a background NEI-related miRNA-TF regulatory network (NEI-miRTF-N) by integrating NEI signaling molecules (including miRNAs, genes, and TFs) and identifying miRNA-TF feed-forward loops. Our analysis reveals that the number of immune signaling molecules is the highest and suggests potential directions for signal transduction, primarily from the nervous system to both the endocrine and immune systems, as well as from the endocrine system to the immune system. Furthermore, disease-specific NEI-miRTF-Ns for depression, Alzheimer's disease (AD) and dilated cardiomyopathy (DCM) were constructed based on the known disease molecules and significantly differentially expressed (SDE) molecules. Additionally, we proposed a novel method using depth-first-search algorithm for identifying significantly dysregulated NEI-related miRNA-TF regulatory pathways (NEI-miRTF-Ps) and verified their reliability from multiple perspectives. Our study provides an effective approach for identifying disease-specific NEI-miRTF-Ps and offers new insights into the synergistic regulation of miRNAs and TFs within the NEI network. Our findings provide information for new therapeutic strategies targeting these regulatory pathways., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) affect millions of people worldwide. Curative treatment for these neurodegenerative disorders is still lacking and therefore a further understanding of their cause and progression is urgently needed. Extracellular vesicles (EVs) are nanosized vesicles loaded with cargo, such as proteins and miRNAs, that are released by cells and play an important role in intercellular communication. Intercellular communication through EVs can contribute to the spread of pathological proteins, such as amyloid-beta and tau, or cause pathogenesis through other mechanisms. In addition, EVs may serve as potential biomarkers for diagnosis and for monitoring disease progression. In this review, we summarize and discuss recent advances in our understanding of the role of EVs in AD, ALS an PD with an emphasis on dysregulated cargo in each disease. We highlight shared dysregulated cargo between these diseases, discuss underlying pathways, and outline future implications for therapeutic strategies., Competing Interests: Declarations. Conflict of interest: R.J.P. reports to have sponsored research agreements with Amylyx., (© 2024. The Author(s).)

We studied the expression levels of microRNAs (miR-21, miR-27a, miR-221, and miR-429) in the thymus of female Wistar rats after surgical treatment of breast cancer (BC) and after photodynamic therapy for BC followed by tumor resection. In the group without treatment, the levels of pro-oncogenic miR-21, miR-27a, and miR-221 in the thymus were reduced in comparison with those in the group of intact control. After surgical treatment of BC, the levels of miR-21 and miR-27a in the thymus increased in comparison with those in BC without treatment. Surgical removal of the tumor followed by photodynamic therapy led to an even greater increase in the levels of miR-21 and miR-27a in the thymus in comparison with those in the group of surgical treatment alone. Expression of the tumor-suppressive miR-429 in the thymus significantly exceeds the levels in the BC without treatment and BC+surgery groups., (© 2025. Springer Science+Business Media, LLC, part of Springer Nature.)

Non-small cell lung cancer (NSCLC) is the most prevalent histology type of lung cancer worldwide, accounting for 18% of total cancer-related deaths estimated by GLOBOCAN in 2020. CircRNAs have emerged as potent regulators of NSCLC development. CircRANGAP1 (hsa&#95;circ&#95;0001235/hsa&#95;circ&#95;0063526) is a potential biomarker for NSCLC identified by microarray dataset analysis. Here, we investigated the biological functions of circRANGAP1 in NSCLC development and elucidated the associated competing endogenous RNA (ceRNA) mechanisms. We found that circRANGAP1 expression was upregulated in NSCLC tissues and cells, which was inversely correlated with carcinogenesis and poor clinical outcome of NSCLC patients. CircRANGAP1 knockdown inhibited NSCLC migration by regulating miR-512-5p/SOD2 axis. In conclusion, circRANGAP1 facilitated NSCLC tumorigenesis and development by sponging miR-512-5p to upregulate SOD2 expression. Suppression of circRANGAP1 expression by si-circRANGAP1 treatment could be a strategy to inhibit NSCLC development and metastasis., Competing Interests: Declarations Conflict of interest The authors declare that there is no conflict of interest. Ethical Approval All experimental protocols were approved by the Ethics Committee of Traditional Chinese Medicine Hospital of Jiashan and written informed consent was obtained from all participants. Consent for Publication All patients in this study provided their consent for publication., (© 2023. The Author(s).)

Disorders of glucose and lipid metabolism are an important cause of type 2 diabetes mellitus (T2DM). Identifying the molecular mechanism of metabolic disorders is key to the treatment of T2DM. The study was to investigate the effect of circRNA PIP5K1A (circPIP5K1A) on glucose and lipid metabolism and inflammation in T2DM rats. A T2DM rat model was established, and then the T2DM rats were injected with lentiviral vectors that interfere with circPIP5K1A, miR-552-3p, or ENO1 expression. Fasting blood glucose (FBG) and fasting insulin (FINS) levels of rats were detected by an automatic analyzer and insulin detection kit, and HOMA-IR was calculated. Lipid metabolism was assessed by measuring serum levels of TG, TC, LDL-C, leptin, and resistin. Serum levels of inflammatory factors (TNF-α and IL-6) were detected by ELISA. The pathological conditions of pancreatic tissue were observed by HE staining. circPIP5K1A, miR-552-3p and ENO1 levels were recorded. The experimental results showed that circPIP5K1A and ENO1 were up-regulated, and miR-552-3p was down-regulated in T2DM rats. Down-regulating circPIP5K1A or up-regulating miR-552-3p reduced blood glucose and lipid levels, inhibited inflammation, and improved pancreatic histopathological changes in T2DM rats. In addition, up-regulating ENO1 rescued the ameliorating effects of down-regulated circPIP5K1A on T2DM rats. In general, downregulating circPIP5K1A improves insulin resistance and lipid metabolism disorders and inhibits inflammation by targeting miR-552-3p to mediate ENO1 expression., Competing Interests: Declarations Conflict of Interests Authors declared no conflict of interest. Ethical Statement All animal experiments were complied with the ARRIVE guidelines and performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The experiments were approved by the Institutional Animal Care and Use Committee of Changshu Hospital Affiliated to Soochow University., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa&#95;circ&#95;0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development. The study enrolled 165 normal pregnancies and 165 pregnancies with gestational hypertension. The significance of hsa&#95;circ&#95;0088196 in discriminating gestational hypertension, predicting PE, and predicting adverse pregnancy outcomes was evaluated based on its serum expression. The effect and mechanism of hsa&#95;circ&#95;0088196 in HUVEC injury were assessed by CCK8, Transwell, ELISA, and western blotting. Significant downregulation of hsa&#95;circ&#95;0088196 could distinguish gestational hypertension pregnancies and predict the risk of PE. Gestational hypertension pregnancies developed PE showed a lower serum hsa&#95;circ&#95;0088196 level, which also discriminated PE patients, predicted severe conditions and adverse pregnancy outcomes. Overexpressing hsa&#95;circ&#95;0088196 alleviated the enhanced proliferation, migration, inflammation, and angiogenesis by hypoxia/reoxygenation (H/R), which was reversed by miR-145-5p. Silencing miR-145-5p showed similar effects on H/R-induced endothelial cell injury, which was reversed by FLT1. Moreover, FLT1 was positively regulated by hsa&#95;circ&#95;0088196, indicating its involvement in the regulation of HUVEC injury by hsa&#95;circ&#95;0088196. Reduced serum hsa&#95;circ&#95;0088196 served as a biomarker for the diagnosis of gestational hypertension, risk evaluation of PE, and the prediction of adverse pregnancy outcomes. hsa&#95;circ&#95;0088196 suppressed endothelial cell injury induced by H/R through modulating the miR-145-5p/FLT1 axis., Competing Interests: Declarations. Competing Interests: The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

This study leveraged microarray datasets to investigate differentially expressed genes (DEGs) in cumulus cells and their relevance in predicting the successful implantation of embryos in human in-vitro fertilization procedures. The microarray data were obtained from the GEO database, encompassing samples of cumulus cells during in vitro culture and different passages. To ensure data consistency, inter-batch normalization was performed, and Principal Component Analysis (PCA) was applied to assess the impact of normalization on sample group clustering. The integrated dataset included samples from cumulus cells during in vitro culture, comprising 17,662 genes. Utilizing the "limma" software package, 1906 DEGs were identified, with 437 genes downregulated and 589 genes upregulated in the cumulus cells of infertility cases, while 748 genes were upregulated, and 1317 genes were downregulated in cumulus cells of successful implantation cases. Functional enrichment analysis utilized Gene Ontology, Metascape, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment tools. Biological processes and molecular functions were enriched, including protein targeting, mRNA processing, and molecular binding among the identified DEGs. Furthermore, target prediction and functional enrichment analysis of microRNAs (miRNAs) revealed 25 key genes and 13 relevant miRNAs were identified. Notably, hsa-miR-149, hsa-miR23b, hsa-miR-877, hsa-miR593, hsa-miR-18a, hsa-miR25, hsa-miR185, mmu-miR-207, hsa-miR425, hsa-miR214, hsa-miR-129, hsa-miR-629, and hsa-miR-194 emerged as the most prominent miRNAs with potential regulatory roles in successful embryo implantation. This comprehensive analysis provides valuable insights into the molecular mechanisms underlying embryo implantation, offering potential targets for further research and therapeutic interventions in assisted reproductive technologies., Competing Interests: Declarations. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflicts of interest/Competing Interests: The authors declare no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

The current study aims to evaluate the levels of miR-34a, RASSF1A, and E-cadherin in relation to the levels of isoform B of progesterone receptor (PRB) in endometrioid carcinoma (EC) and atypical hyperplasia (AEH) and their association with clinicopathological parameters. 105 cases (35 EC, 35 AEH, and 35 control) were involved in this study. Cases of AEH received treatment, and other samples were obtained after 6 months to assess the response. E-cadherin and PRB were assessed by immunohistochemistry (IHC), RASSFA methylation by MSP-PCR, and its serum level by ELISA and miR-34a via quantitative PCR. The expressions of miR-34a, RASSF1A, E-cadherin, and PRB differ among the studied groups; all were higher in normal compared with AEH and EC, with a statistically significant difference. The higher PRB expression and decreased miR-34a and RASSF1A expression were associated with resistance to hormonal therapy in AEH. High PRB in EC is associated with lower RASSFA1, E-cadherin, and miR-34a. Decreased expressions of RASSF1A, miR-34a, and E-cadherin had a significant connection to advanced stages. Expression of PRB and miR-34a and serum levels of RASSF1A predict response to treatment in cases of AEH. High PRB and low E-cadherin expression are associated with progressive disease in EC., (© 2024. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

microRNAs (miRNAs) have a serious and dynamic function in spermatogenesis. These molecules have been recognized as crucial parts of the control of gene activity, and their involvement in the regulation of target genes has been extensively studied. This research aimed to determine the expression of CRISP3 and miR-493-5p, miR-204-5p, and miR-182-5p in the seminal plasma fluid and spermatozoa and to examine the relationship between CRISP3 and the mentioned miRNAs in 57 infertile men with Asthenozoospermia (AZ) (n = 19), Teratoasthenozoospermia (TAZ) (n = 19), and Normozoospermia (NZ) (n = 19). The selection of these three miRNAs, miR-493-5p, miR-204-5p, and miR-182-5p, was conducted using computational prediction algorithms. These miRNAs were nominated as CRISP3-associated miRNAs that can target CRISP3. We performed the quantitative real-time polymerase chain reaction (qRT-PCR) method to determine the levels of the studied miRNA expression. In the following stage, the expression of two protein isoforms of CRISP3, targeted by these miRNAs, was quantified using western blotting. The results demonstrate significant differences in the levels of miR-182-5p, miR-204-5p, miR-493-5p, and CRISP3 isoforms among the patient groups. In TAZ individuals, miR-182-5p and miR-204-5p expression decreased, while miR-493-5p expression increased compared to the control samples. Additionally, significant differences were observed in the expression levels of unglycosylated and glycosylated CRISP3 isoforms between the AZ and NZ groups. Correlation analysis revealed associations between miRNA expression and the expression of CRISP3 isoforms in the patient groups. Additionally, there were correlations between the expression of CRISP3 isoforms and sperm motility and morphology. These results offer valuable insights into the underlying molecular processes associated with male infertility., Competing Interests: Declarations. IRB Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the ethics committee of Shahrekord University of Medical Sciences (ethics code: IR.SKUMS.REC.1397.172). Competing Interest: All authors declare no potential competing interest., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Gastric cancer (GC) is a malignant tumor with the highest incidence among all kinds of malignant tumors in China. Long noncoding RNAs (LncRNAs) have been reported to act as microRNA (miRNAs) sponges and thus play key roles in biological processes and pathogenesis. Thus, this study aimed to investigate the functional effects and the regulatory mechanism of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in gastric cancer cells. The expression of OIP5-AS1, miR-140-5p, Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were assessed using Cell-Counting Kit-8 (CCK-8), Flow cytometry, and Transwell assays. UBR5 protein level was detected by Western blot. Binding between miR-140-5p and OIP5-AS1 or UBR5 was predicted by Starbasev2.0 and TargetScan, and verified using Dual-luciferase reporter assays and RNA pull-down assay. A xenograft mice model was used to evaluate the effects of OIP5-AS1 on tumor growth in vivo. OIP5-AS1 was upregulated in GC cancer and cells. OIP5-AS1 knockdown inhibited cell proliferation, migration, invasion, but induced cell apoptosis in GC. In mechanism, OIP5-AS1 might serve as a sponge for miR-140-5p to enhance UBR5 expression. Moreover, overexpression of miR-140-5p or UBR5 partly reversed the effects of OIP5-AS1 depletion on the progression of GC cells. Furthermore, OIP5-AS1 depletion also suppressed tumor growth in vivo. OIP5-AS1 silencing might suppress proliferation, migration, invasion, and induced apoptosis in GC cells by regulating the miR-140-5p/UBR5 axis., Competing Interests: Declarations Conflict of interest The authors declare that they have no competing interest., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To investigate the impacts of circ&#95;0069094 on acute coronary syndrome. Real-time polymerase chain reaction was used to detect the expression levels of circ&#95;0069094, and its diagnostic performance was evaluated using ROC curve. Spearman's method was performed for correlation analysis. The levels of SOD, MDA, vWF in ACS rat models were assessed by commercial kits. The activities of H/R cell models were detected by CCK-8, Transwell, flow cytometry. The GO and KEGG were performed to analyze the function of targeted genes of miR-484. The concentration of circ&#95;0069094 was decreased in patients with ACS, ACS rat models and H/R HUVEC models. The dysfunction of SOD, MDA, vWF, LVIDs, LVDD, and LVEF in the ACS models was regulated by the increase of circ&#95;0069094. The viability, migration, apoptosis of the H/R models were regulated by circ&#95;0069094. MiR-484 was a ceRNA of circ&#95;0069094 and mediated the function of circ&#95;0069094., Competing Interests: Declarations. Conflict of interest: None. Human subjects/informed consent statement: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study was to investigate the mechanism of Changma Xifeng tablet, a traditional Chinese medicine in the treatment of Tourette syndrome. Network pharmacology was utilized to pinpoint blood-entering constituents of Changma Xifeng and explore their potential targets. Additionally, differential microRNA expression analysis was conducted to predict Tourette syndrome-associated targets, complemented by molecular docking and dynamics simulations to support the interactions of the active compounds with these targets. The study identified 98 common targets between Changma Xifeng and Tourette syndrome, which may be involved in the treatment process. A protein-protein interaction network and a drug-active ingredient-disease target network highlighted the formulation's multi-component, multi-target therapeutic approach. Eight pivotal targets-AR, GRM5, MET, RORA, HTR2A, CNR1, PDE4B, and TOP1-were identified at the intersection of microRNA and drug targets. Molecular docking revealed 12 complexes with favorable binding energies below - 7 kcal/mol, specifically: AR with Alfacalcidol, TOP1 with Albiflorin, GRM5 with Arachidic Acid, GRM5 with Palmitic Acid, AR with Arachidic Acid, AR with 2-Hydroxyoctadecanoic Acid, RORA with Pinellic Acid, RORA with Palmitic Acid, AR with Acoronene, AR with Epiacoronene, AR with 4,4'-Methylenediphenol, and HTR2A with Calycosin. Our molecular docking and molecular dynamics simulations suggest potential stable interactions between the formulation's active components and target proteins. These computational methods provide a preliminary theoretical framework that will guide our future experimental work. The study provides a scientific rationale for the use of traditional Chinese medicine in Tourette syndrome management and offers new insights for drug development., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mono-butyl phthalate (MBP), the metabolite of dibutyl phthalate (DBP), is the most abundant phthalate metabolite found in Chinese women. Extracellular vesicles (EVs) are nanoscale lipid bilayer particles produced by extensive kinds of cells, serving a key role in intercellular communication. Extracellular vesicle miRNAs (EV-miRNAs) in follicular fluid (FF) have been evidenced to be associated with female reproductive health. The objective of this study was to investigate the associations of EV-miRNAs expressed profile with DBP exposure in FF of female participants and expose its potential mechanism in impaired oocyte development. Based on participants' FF MBP concentrations and fertilization status, we compared the miRNA expression between the FF-EVs of group A (high DBP exposure and impaired fertilization) and group B (low DBP exposure and normal fertilization). Compared with group B, miR-1246, miR-3679-5p, miR-423-5p, miR-5585-3p, miR-116-5p, miR-172-5p were upregulated, while miR-34b-3p was downregulated in group A. Target genes of the differently expressed miRNAs were predicted, and the functional analysis was performed. Furthermore, we exposed human ovarian granulosa tumor cell line (KGN) to MBP (4ug/L) to isolate the EVs from the culture medium and validated the expression levels of different miRNAs. We found that MBP exposure was significantly associated with increased levels of miR-116-5p (P = 0.01). In addition, we demonstrated that the most different miRNA, miR-116-5p regulated oocyte fertilization by inhibiting FOXO3a. Our findings suggested that EV-miRNAs in the FF might mediate MBP toxicity in oocytes., Competing Interests: Declarations. Ethics Approval: All included patients gave their oral and written informed consent. The study project was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (No. TJ-IRB20180607; No.TJH-202306063). Consent to Participate: Informed consent was obtained from all individual participants included in the study. Consent for Publication: Not applicable. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)