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Background: Diabetic nephropathy (DN) is one of the most common and serious microvascular complications associated with diabetes. DN is the leading contributor to the majority of cases of end-stage renal disease (ESRD). Small extracellular vesicles (sEVs) can transport various genetic materials to recipient cells. The objective of this study was to explore how sEVs released from HK-2 cells when stimulated by high glucose levels influence renal tubular phenotypic transformation through miR-21-5p., Methods: Both human and cell studies were utilized to explore the crosstalk between proximal renal tubules in DN. sEVs from plasma and cells were isolated using ultracentrifugation, and the differential expression of miR-21-5p in plasma sEVs from DN patients versus healthy controls was quantified using Quantitative Real-time PCR (RT-qPCR). A DN model was constructed by stimulating HK-2 cells with glucose. The expression of epithelial-mesenchymal transition (EMT) proteins in each cell group was analyzed by Western Blot (WB), while miR-21-5p levels in both cells and their sEVs were quantified using RT-qPCR. A stable transfected HK-2 cell line was constructed. The CCK8 assay, scratch assay, and WB were employed to detect EMT proteins, aiming to explore how autocrine sEVs affect tubular phenotypic transformation in diabetic nephropathy (DN)., Results: The expression of miR-21-5p in plasma sEVs was significantly elevated in the DN group compared to the healthy control group. High glucose (HG) stimulation of HK-2 cells resulted in higher miR-21-5p expression in both cells and their sEVs, leading to enhanced proliferation, migration, and EMT capacities in these cells. Co-incubation of HK-2 cells with HG-sEVs significantly enhanced the proliferation, migration, and EMT capabilities of the recipient cells, but miR-21-5p knockdown reversed these effects., Conclusion: These results indicate that high glucose stimulates HK-2 cells to secrete sEVs, which promote DN proliferation, migration, and EMT through miR-21-5p, thereby offering new insights into the treatment of DN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The role of transforming growth factor-beta (TGF-β) is dual, such that, it inhibits tumor development in initial stage and promotes metastasis in later stage. The present study is aimed to analyse the relevance of different types of TGF-β and their receptors on the overall survival (OS) and TGF-β driven gene expression in individuals with cervical cancer (CC) using ONCODB and GEPIA databases. The in-silico gene expression analysis showed, TGF-β1 and TGFβR2 are upregulated in cells infected with human papilloma virus (HPV)16, whereas, TGF-β2, TGFβR1 and TGFβR3 expression were downregulated. In HPV 18 infected cells, TGF-β1, TGF-β2 and TGFβR1 were downregulated, meanwhile, TGF-β3, TGFβR2 and TGFβR3 were upregulated. OS analysis of CC patients with different TGF-β expression revealed that, TGF-β1, TGF-β2, TGF-β3 and TGFβR2 were associated with reduced survival rate. Further, we identified four microRNAs (miRNAs) (hsa-miR-21-5p, hsa-miR-29b-3p, hsa-miR-101-3p and hsa-miR-130a-3p) interacted favorably with TGF-β in HPV 16 and 18 positive samples using MIENTURNET. This present review further emphasizes that, targeting TGF-β could be a novel and futuristic approach for CC management and therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

miR408 is a conserved plant miRNA family that is known to regulate genes involved in copper metabolism. However, the function of miR408 in maize leaf growth regulation under cold stress isn't defined. In this study, endogenous maize miR408 was transiently silenced by using virus-induced gene silencing (VIGS) combined with short tandem target mimic (STTM) approaches. To this end, STTM-miR408a/b was designed, synthesized, and applied to maize seedlings. Subsequently, STTM-miR408a/b (STTM) and mock-treated (M) seedlings were subjected to cold stress (C) and the growth response of the seedlings was monitored. Finally, STTM-miR408a/b-treatment successfully downregulated the expression of endogenous mir408a/b and upregulated their putative targets Basic Blue Protein (BBP) and Blue Copper Protein (BCP) antagonistically in the STTM and STTM_C groups compared to M and M_C groups. On the other hand, their putative target Laccase (LAC22) gene was upregulated in the STTM group compared to the M group, but there were no significant expression differences between the M_C and STTM_C groups. The elongation rate of the STTM-miR408a/b-treated second and third leaves was reduced by 10% and 19% resulting in 19% and 11% shortening, respectively. Furthermore, the activity of catalase (CAT) and glutathione reductase (GR) was decreased by 57% in STTM, M_C, and STTM_C, and 29% and 28% in the M_C and STTM_C groups and ascorbate peroxidase (APX) was increased by 15% in M_C and STTM_C groups, respectively. These findings illuminated the maize leaf growth response to cold via regulation of expression of miR408 and its target genes and antioxidant system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Long non-coding RNAs (lncRNAs) play important roles in progression of neuroblastoma (NB). LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to affect the development of multiple tumors. However, the effect of NEAT1 on NB remain unclear. In this study, the new mechanisms whereby how NEAT1 influences tumor progression in NB was investigated., Methods: RT-qPCR, western blot, bioinformatics, cell growth, Transwell, and flow cytometric analyses were performed to determine how NEAT1 synchronously regulates the miR-873-5p/MYCN proto-oncogene(MYCN) and miR-873-5p/polypeptide N-acetylgalactosaminyltransferase 1(GalNAcT-I) axes to accelerate the progression of NB. NB-bearing animal models were established to evaluate the function of NEAT1 in NB. The relationships between transcription factor coactivatorassociated arginine methyltransferase 1 (CARM1) and NEAT1, NEAT1 and miR-873-5p, miR-873-5p and GalNacT-I or MYCN, were verified using luciferase reporter gene assay, respectively., Results: Our study revealed elevated levels of NEAT1 expression in NB cells and tissues which was associated with an advanced pathological stage and poor prognostic outcomes. According to in vitro gain- and loss- of function experiments, NEAT1 enhances progression of NB. NEAT1 silencing was found to inhibit NB proliferation in vivo. Mechanistically, to achieve upstream regulation, epigenetic downregulation of NEAT1 was achieved via the inhibition of CARM1. NEAT1 was found to positively regulate MYCN and GalNAcT-I levels as a competitive sponge of miR-873-5p., Conclusion: Activity of the lncRNA NEAT1 can be triggered via CARM1, which synchronously promotes NB development via the miR-873-5p/MYCN and miR-873-5p/GalNAcT-I axes. These findings shed light on the novel molecular mechanisms underlying NB progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of LncRNA SNHG20 on epithelial mesenchymal transition (EMT) and microtubule formation in human oral squamous cell carcinoma (OSCC) cells through targeted regulation of the miR-520c-3p/ RAB22A pathway., Methods: After real-time fluorescence quantitative detection of LncRNA SNHG20, miR-520c-3p, RAB22A mRNA expression levels in OSCC tissues and cells, dual luciferase reporter assay was used to detect the relationship between the three. OSCC cells were randomly separated into control group, sh-NC group, sh-SNHG20 group, sh-SNHG20+anti NC group, and sh-SNHG20+anti miR-520c-3p group. Western blotting was used to detect the expression of N-cadherin, vimentin, and E-cadherin proteins in the OSCC cells. The morphology of HSC-3 cells was observed under microscope. Changes in the number of microtubules formed were detected. The effect of LncRNA SNHG20 on the growth of OSCC tumors and the expression levels of LncRNA SNHG20, miR-520c-3p and RAB22 A in the transplanted tumors were detected by nude mice tumorigenesis experiment., Results: LncRNA SNHG20 and RAB22A mRNA were upregulated in the OSCC tissues and cells, while miR-520c-3p was downregulated ( P < 0.05). There were binding sites between LncRNA SNHG20 and miR-520c-3p, RAB22A and miR-520c-3p, which had targeted regulation relationship. Compared with the sh-NC group, the sh-SNHG20 group had fewer stromal like cells, more epithelial like cells, incomplete microtubule structure, and fewer nodules. LncRNA SNHG20, RAB22A, N-Cadherin, and vimentin were downregulated, while miR-520c-3p and E-cadherin were upregulated ( P < 0.05). Compared with the sh-SNHG20+anti-NC group, the sh-SNHG20+anti-miR-520c-3p group had a higher number of stromal like cells, a lower number of epithelioid cells, tighter microtubule arrangement, and more microtubule nodules. miR-520c-3p and E-cadherin were downregulated, while RAB22A, N-cadherin, and vimentin were upregulated ( P < 0.05). The transplanted tumor of OSCC in sh-SNHG20 group was smaller and lower than that in sh-NC group. The expression levels of LncRNA SNHG20 and RAB22A in the transplanted tumor tissues were lower than those in sh-NC group, and the expression level of miR-520c-3p was higher than that in sh-NC group ( P < 0.05)., Conclusion: LncRNA SNHG20 promotes epithelial-mesenchymal transition and microtubule formation in human oral squamous cell carcinoma cells by targeting the miR-520c-3p/ RAB22A pathway. Inhibiting the expression of LncRNA SNHG20 can target and regulate the miR-520c-3p/ RAB22A pathway to inhibit EMT and microtubule formation in OSCC cells.

In previous reports, we highlighted the significant involvement of SMYD3, a histone methyltransferase (HMT), in various aspects of cancer progression, including cell adhesion, migration, and invasion. In this study, we delved deeper into understanding the relationship between SMYD3 and epithelial-mesenchymal transition (EMT) both in cell lines and clinical samples. Our investigation uncovered a notable correlation between heightened SMYD3 expression and the presence of EMT markers in human breast cancer tissues. We found that the induction of SMYD3 expression is facilitated by transforming growth factor beta 1 (TGF-β1), which achieves this by suppressing miR-124, an inhibitor that targets SMYD3, through alterations in DNA methylation. Conversely, our experiments demonstrated that reducing SMYD3 levels through RNA interference impeded TGF-β1-induced EMT in breast cancer cells. Furthermore, our results revealed that SMYD3 alone has the capability to modulate the expression of markers associated with EMT. An intriguing aspect of our study is the revelation that SMYD3 influences the activation of vimentin by binding to its response elements within the core promoter region. Notably, this effect is independent of SMYD3's histone methyltransferase activity. These findings collectively underscore the pivotal role of SMYD3 in driving EMT, both in cell lines and primary cancer tissues, particularly emphasizing its significance in TGF-β1-induced EMT in breast cancer., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Aims: Endometriosis development is associated with peritoneal immune microenvironment abnormality; however, the specific mechanism is uncertain. We aimed to investigate the effects and underlying mechanisms of uterine cavity-derived exosomes on macrophage polarization and endometriosis progression., Materials and Methods: Uterine cavity-derived exosomes, miR-210-3p inhibitor or siATP5D were used to treat macrophages. Then evaluated the polarization of macrophages. By co-culturing of treated macrophages with endometrial stromal cells in vitro and an endometriosis C57BL6 mouse model to assess the role of uterine-derived exosomes and macrophages in the development of endometriosis., Key Findings: Uterine cavity-derived exosomes could increase miR-210-3p expression and induce M2 macrophage polarization. Mechanistically, miR-210-3p can restrict ATP5D expression in macrophages, which leads to M2 polarization. In vivo experiments confirmed that macrophages lentivirally transduced with miR-210-3p can significantly decrease the growth and implantation of mouse endometriosis., Significance: In summary, our findings suggest that exosomes derived from the uterine cavity may drive macrophages towards M2 and promote endometriosis progression via miR-210-3p/ATP5D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Aims: Gestational diabetes mellitus (GDM) provides offspring with a hyper-metabolic intrauterine microenvironment. In this study, we aimed to identify key differential microRNAs in GDM-derived exosomes and explore the potential mechanisms of abnormal embryonic development of islets in offspring., Main Methods: Exosomes were extracted from umbilical vein blood of GDM and non-GDM (NGDM) parturients for microRNA sequencing. Offspring islets were collected on E18.5 and P0 to detect the expression and location of key proteins by immunofluorescence. Target binding of miR-7-19488 and PIK3R2 mRNA was verified using a dual-luciferase reporter assay. The miR-7-19488-mimic, PI3K/mTOR inhibitors were used to treat primarily islet cells to explore the relationship among miR-7-19488, PI3K, and Akt-FoxO1/mTORC1 signaling. The miR-7-19488 agomir was synthesized for further in vivo validation., Key Findings: GDM-derived exosomes caused the overdevelopment of offspring-islets at E18.5 with an increased production of insulin and glucagon co-staining cells, increased number of α cells synthesizing GLP-1, and stimulation of mTORC1 singling, which were more serious at birth. The up-regulated miR-7-19488 in GDM-exosomes targeted PIK3R2 mRNA, leading to translation stagnation of p85β and activation of PI3K-Akt singling in fetal islets. Importantly, the activated PI3K-Akt-FoxO1 singling promoted development and differentiation of α and β cells and enhanced the GLP-1/GLP-1R axis, which cooperates with miR-7-19488 to activate PI3K-Akt-FoxO1/mTORC1 signaling, leading to the early initiation of the functional maturation of overdeveloped β cells., Significance: miR-7-19488 loaded in GDM-derived exosomes induce the abnormal overdevelopment and functional maturation of fetal islets, which is one of the contributors of high incidence of diabetes in adulthood., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2025. Published by Elsevier Inc.)

Renal ischemia-reperfusion injury (IRI) is a prevalent cause of acute kidney injury, however, the regulatory mechanisms of miR-374b-5p in renal IRI remain poorly understood. We established hypoxia/reoxidation (H/R)-induced renal injury models using HK-2 and TCMK-1 cells, as well as an ischemia-reperfusion (I/R)-induced mouse model. Renal tubular epithelial cells (RTECs) viability and apoptosis were assessed using CCK-8, flow cytometry, and TUNEL assays. The targeting relationship between miR-374b-5p and SRSF7 was analyzed using dual luciferase reporter assays. The interaction between METTL3 and miR-374b-5p was confirmed through methylated RNA immunoprecipitation (MeRIP) and co-immunoprecipitation (Co-IP) assays. We found that miR-374b-5p levels were significantly upregulated in H/R-induced HK-2 and TCMK-1 cells. Furthermore, miR-374b-5p promoted H/R-induced RTEC injury by suppressing cell viability and exacerbating apoptosis. SRSF7 was identified as a downstream target of miR-374b-5p, inhibition of SRSF7 reversed the inhibitory effects of miR-374b-5p inhibitors on RTEC injury. Additionally, METTL3 interacted with the microprocessor protein DGCR8 and modulated the processing of pri-miR-374b-5p in an m6A-dependent manner. In the renal IRI model, METTL3 and miR-374b-5p levels were upregulated, and knockdown of METTL3 inhibited apoptosis in H/R-induced HK-2 and TCMK-1 cells. Conversely, miR-374b-5p reversed the protective effects of METTL3 knockdown on renal IRI. Our findings provide novel insights into the role of m6A methylation in the development of renal IRI, demonstrating that METTL3 promotes renal IRI by modulating the miR-374b-5p/SRSF7 axis., (© 2025 Federation of American Societies for Experimental Biology.)

Aims: Remodeling of the extracellular matrix (ECM) is critical for effective wound healing and maintaining organ homeostasis. The ECM of soft tissues, including cardiac, contains embedded nanovesicles; or matrix-bound nanovesicles (MBV). The luminal cargo of MBV consists of lipids, microRNAs (miRNAs), and proteins that influence the function of immune and stromal cells. ECM remodeling is extensive during heart disease, yet it is unknown if MBV are altered during the development of heart disease. We conducted the present study to answer this question., Methods and Results: MBV were isolated from de-identified human left ventricle (LV) tissue samples from: 1) non-ischemic, failing hearts (failing) and 2) non-failing, non-ischemic hearts (control). MBV morphology was analyzed and the protein and miRNA cargo were quantified. Immunomodulatory capacity of MBV was assessed on macrophages. Failing and control heart tissue had similar concentrations of MBV, however, their size and cargo differed. MBV from failing tissue had increased levels of Apolipoprotein A-1 and decreased levels of C-Reactive Protein. Over 600 unique miRNA were detected. Of these, 5 % showed significantly different levels, with most being downregulated in MBV from failing heart tissue. Ex vivo stimulation of human macrophages with MBV isolated from control ventricular tissue, but not failing ventricles, induced gene expression suggesting increased reparative functions., Conclusion: These data reveal that MBV are present within the human heart and suggests that disease progression alters MBV cargo (lipids, microRNAs, and proteins). Furthermore, it is suggested that alterations in local MBV cargo may perpetuate pathology when their capacity to modulate reparative immune cells is diminished., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Airborne ultrafine particulate matter (PM 0.1 ) can enter the brain, induce microglia activation, and promote the development of Alzheimer's disease (AD). Circular RNAs (circRNAs) are also involved in AD pathogenesis. However, the role of AD-related circRNAs in PM 0.1 -induced microglia activation remains unclear. Therefore, we explore cytotoxicity, microglia activation, and AD-associated circRNA expression in human microglial HMC3 cells treated with PM 0.1 , and further examined circRNA expression in mice and cognitively impaired individuals. The results revealed that PM 0.1 exposure decreased cell viability, increased lactate dehydrogenase activity, caused microglia activation, elevated microglial M1 maker expression, downregulated microglial M2 maker expression, and reduced AD-related circ&#95;0061183 expression in vitro. Functionally, circ&#95;0061183 silencing enhanced microglia activation and microglial M1 polarization, but inhibited microglial M2 polarization. Mechanistically, circ&#95;0061183 can bind to miR-98-5p to co-regulate M2 microglial-related IL10 expression, which may affect transforming growth factor-β signaling to regulate PM 0.1 -inhibited microglial M2 polarization. Moreover, circ&#95;0061183 downregulation was observed in the brain of PM 2.5 -exposed mice and AD mice and in the blood of cognitively impaired individuals. Furthermore, circ&#95;0061183 was positively related to mini-mental state examination scores and amyloid-β42 peptide expression in elderly individuals. Overall, the current work offers epigenetic insights into the regulatory mechanisms of circRNAs on microglial activation caused by environmental pollutants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Danggui Buxue Decoction (DBD) is a classic traditional Chinese herbal formulation, composed of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) in a ratio of 5:1. It is a traditional Chinese medicine classic prescription for nourishing Qi and Yin (vital energy and body fluids), and it is effective in treating various clinical diseases. Diabetic nephropathy (DN) is categorized under "thirsting," "edema," and "turbid urine" in Traditional Chinese Medicine (TCM). However, the underlying mechanisms by which DBD ameliorates diabetic nephropathy remain unclear., Aim of the Study: To explore the mechanism by which Danggui Buxue Decoction (DBD) regulates podocyte autophagy in diabetic nephropathy (DN)., Methods: Male db/m mice served as controls; db/db mice were divided into the model, dapagliflozin, and high/low-dose DBD groups. After 12 weeks of gavage, body weight, fasting blood glucose, urine albumin-to-creatinine ratio, 24-h urine volume, and blood urea nitrogen were recorded. Renal autophagy was assessed by Masson staining; mRNA levels were measured by qRT-PCR; and protein expression was analyzed by Western blot. The expression of inflammatory factors in the kidney was measured by ELISA. Human renal podocytes were cultured in NG, HG, HG + Blank serum, and HG + DBD-containing serum groups for 48 h; cell viability was measured by CCK-8, and autophagy was observed by transmission electron microscopy. Changes in autophagy protein and mRNA expression were observed after miR-27a transfection under high glucose conditions., Results: DBD can ameliorate renal function and reduce the degree of renal fibrosis in DN mice, enhance the mRNA expression of Beclin-1 and ULK1, and decrease the mRNA expression of Vimentin and α-SMA. This trend mirrors protein expression, and DBD also lowers renal inflammatory factors. DBD-containing serum boosts human renal podocyte viability under high glucose, protecting cells and modulating mRNA levels of Beclin-1, ULK1, P62, and PI3K, with miR-27a-mimic reversing these effects. DBD-containing serum also enhances Beclin-1, suppresses P62, and reduces the expression of p-PI3K/PI3K and p-AKT/AKT., Conclusion: DBD Regulates Autophagy to Improve Renal Fibrosis in Diabetes via the miR-27a/PI3K/AKT Pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Colorectal cancer (CRC) represents a common type of carcinoma with significant mortality rates globally. A primary factor contributing to the unfavorable treatment outcomes and reduced survival rates in CRC patients is the occurrence of metastasis. Various intricate molecular mechanisms are implicated in the metastatic process, leading to mortality among individuals with CRC. In the realm of intercellular communication, exosomes, which are a form of extracellular vesicle (EV), play an essential role. These vesicles act as conduits for information exchange between cells and originate from multiple sources. By fostering a microenvironment conducive to CRC progression, exosomes and EVs significantly influence the advancement of the disease. They contain a diverse array of molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids, and transcription factors. Notably, ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are prominently featured within exosomes. These ncRNAs have the capacity to regulate various critical molecules or signaling pathways, particularly those associated with tumor metastasis, thereby playing a crucial role in tumorigenesis. Their presence indicates a substantial potential to affect vital aspects of tumor progression, including proliferation, metastasis, and resistance to treatment. This research aims to categorize exosomal ncRNAs and examine their functions in colorectal cancer. Furthermore, it investigates the clinical applicability of novel biomarkers and therapeutic strategies in CRC. Abbreviations: ncRNAs, non-coding RNAs; CRC, Colorectal cancer; EV, extracellular vesicle; mRNAs, messenger RNAs; miRNAs, microRNAs; lncRNAs, long non-coding RNAs; circRNAs, circular RNAs; HOTTIP, HOXA transcript at the distal tip; NSCLC, non-small cell lung cancer; 5-FU, 5-fluorouracil; OX, Oxaliplatin; PDCD4, programmed cell death factor 4; Tregs, regulatory T cells; EMT, epithelial-mesenchymal transition; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; USP2, ubiquitin carboxyl-terminal hydrolase 2; TNM, tumor node metastasis; TAMs, tumor-associated macrophages; RASA1, RAS p21 protein activator 1; PDCD4, programmed cell death 4; ZBTB2, zinc finger and BTB domain containing 2; SOCS1, suppressor of cytokine signaling 1; TUBB3, β-III tubulin; MSCs, mesenchymal stem cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The aim of this research was to investigate the specific regulatory role of miR-6760-5p in angiogenesis in moyamoya disease., Methods: HUVECs were transfected with miR-6760-5p inhibitor and mimics fragments, then subjected to assays for cell proliferation, migration, and tube formation. Subsequently, downstream target genes of miR-6760-5p were predicted and the protein expression levels of these genes were evaluated. The presence of miR-6760-5p and YAP1 was verified by a dual luciferase reporter gene test, followed by an assessment of the effects of YAP1 and miR-6760-5p on the HUVECs., Results: Comparatively to the control group, increased expression of miR-6760-5p decreased cell growth, movement, and tube formation. YAP1 gene was discovered as a target controlled by miR-6760-5p, with subsequent investigation confirming YAP1 as a gene regulated by miR-6760-5p. Additionally, miR-6760-5p was found to counteract the angiogenesis-promoting effect of YAP1., Conclusion: The results of this research suggest a possible link between the miR-6760-5p gene found in the cerebrospinal fluid of individuals with moyamoya disease and the process of vascularization in this particular condition. The findings indicate that miR-6760-5p may be a new molecular indicator and potential target for the diagnosis of moyamoya disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Artemisia capillaris Thunb. (ACT) is a plant in the Asteraceae family. Its traditional effects are to clear away dampness and heat, promote gallbladder and reduce jaundice. Traditional Chinese medicine believes that MASLD is a damp-heat syndrome. The group's previous study showed that Artemisia capillaris Thunb. Water Extract (ACTE) has an improved effect on MASLD., Aim of the Study and Methods: In order to further understand its mechanism of action, this study established a mouse MASLD model and a HepG2 cell lipid droplet model, combined small RNA sequencing and miRNA transfection experiments, to explore the mechanism of ACTE to improve MASLD by modulating miRNA-targeted mRNA. Non-targeted metabolomics method was used to detect and analyze ACTE., Results: This study screened miR-34a-5p and confirmed its target mRNA-Sirtuin 1 (Sirt1). MASLD induced high expression of miR-34a-5p and low expression of Sirt1, and ACE reversed these changes. When overexpressing miR-34a-5p or knocking down Sirt1, the effect of ACE in reducing PO (palmitic acid and oleic acid complex)-induced lipid accumulation in HepG2 cells was attenuated. ACTE reduces the expression of FASN, SCD1, ACC, and SREBP-1c, promotes the expression of CPT-1 and HSL, thereby reducing lipid accumulation., Conclusions: ACTE activates Sirt1 by inhibiting the expression of miR-34a-5p, thereby reducing liver lipid accumulation and improving HFD-induced MASLD. These findings highlight the potential of ACTE in reducing weight, controlling obesity, and improving lipid metabolism disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: MicroRNAs (miRNAs) are becoming progressively emerging in cancer research from an etiologic and curative point of view. Several miRNAs act as oncogenes or tumor suppressors, which are dysregulated in numerous cancers. Our previous studies have established that nimbolide (a bioactive terpenoid from neem) attenuated hepatocellular carcinoma (HCC) through various mechanisms in mice. Here, we aimed to elucidate the effect of nimbolide in modulating specific miRNAs (21, 145, and 221) and their target genes involved in promoting inflammation and cancer cell proliferation in HCC mice., Methods: Following the induction of HCC in mice at 28 weeks, nimbolide (6 mg/kg b.wt.) was administered orally for four consecutive weeks., Results: We found significantly increased hepatic expression of miR-21a-3p, miR-21a-5p, miR-221-5p and miR-221-3p whilst significantly decreased miR-145a-5p in HCC mice. Nimbolide treatment to HCC mice substantially reduced the miR-21a-5p and miR-221-3p and improved miR-145a-5p gene expression. Our in-silico study also supports these findings. Moreover, hepatic tight junction (TJ) associated proteins such as claudins 1&5 mRNA and protein were increased considerably, whilst significantly decreased hepatic claudin 2 mRNA and protein expression noted in HCC mice. Nimbolide also regulates cadherins, ROCK 1, MMP 9, cyclin D1, CDK4, NF κB and TNFα mRNA expression in HCC mice., Conclusion: We identified for the first time that nibmolide treatment to HCC mice significantly attenuated hepatic miRNAs 21 & 221 expressions and sheltered miR-145 expression. These findings were further confirmed with in-silico studies. Moreover, nibmolide treatment in HCC mice regulates miRNA target genes involved in cancer cell proliferation and inflammation, thereby attenuating HCC progression in mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Obesity is a complex disease marked by increased adiposity and impaired metabolic function. While diet and lifestyle are primary causes, endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), significantly contribute to obesity. BPA, found in plastic consumer products, accumulates in the hypothalamus and dysregulates energy homeostasis by disrupting the neuropeptide Y (NPY)/agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) neurons. However, the precise molecular mechanisms of how BPA disrupts neuropeptide expression remains unclear. We hypothesized that microRNAs (miRNAs), which regulate approximately 60% of the human protein-coding genome and are crucial for hypothalamic energy regulation, may mediate the effects of BPA on Agrp. Using the TargetScanMouse 8.0 and DIANA microT bioinformatics tools, we identified miR-501-5p as a potential miRNA that directly regulates Agrp and the miR-34 family as miRNAs that indirectly regulate Agrp through its transcription factor krüppel-like factor 4 (KLF4). We found that in an immortalized NPY/AgRP-expressing cell line, mHypoE-41, miR-501-5p unexpectedly upregulated Agrp, while miR-34a-5p reduced Klf4 and Agrp mRNA levels. Serum starvation reduced miR-34a-5p levels and elevated Agrp mRNA levels, suggesting a potential role in AgRP regulation. Inhibiting the miR-34a-5p interaction with the Klf4 3'UTR using a specific target site blocker prevented the downregulation of both Klf4 and Agrp, suggesting miR-34a-5p alters Agrp mRNA levels via regulation of KLF4. BPA treatment increased Agrp and Klf4 expression while simultaneously decreasing miR-34a-5p levels, indicating miR-34a-5p may play a role in BPA-mediated dysregulation of Agrp. Overall, this study highlights indirect miRNA-based regulation of Agrp, which can also be dysregulated by obesogens, such as BPA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Gliomas pose a significant global health challenge due to high rates of morbidity and mortality. Recent research has indicated that circular RNAs (circRNAs) may play a crucial role in gliomas. However, the specific impacts of circRNAs on gliomas development is poorly understood. Therefore, the present study aimed to explore the roles of circRNAs in gliomas by analyzing their interactions with microRNAs (miRNAs) and messenger RNAs (mRNAs)., Methods: Datasets were extracted from the Gene Expression Omnibus (GEO) database to investigate differentially expressed circRNAs in gliomas. Using the Circular RNA Interactome, we predicted interactions between the identified circRNAs and 125 target miRNAs, focusing on 15 key miRNAs selected by intersection analysis. The miRNet database was applied to predict 2635 target mRNAs, constructing a comprehensive circRNA-miRNA-mRNA network, while functional enrichment analyses were conducted to determine the roles of this network., Results: Four circRNAs with significant differential expression in glioma samples were identified. The constructed network indicated the substantial involvement of transcriptional regulation and cancer-related pathways. Notably, hsa&#95;circ&#95;0001681 was highlighted as a key circRNA, which was further validated through Sanger sequencing and quantitative reverse transcription PCR (qRT-PCR). Functional assays, including cellular assays and animal xenograft experiments, demonstrated that hsa&#95;circ&#95;0001681 inhibits glioma carcinogenesis in vitro and in vivo., Conclusion: Our investigation highlights the significant role of the circRNA-miRNA-mRNA network in the pathophysiology of gliomas, and supports the potential of hsa&#95;circ&#95;0001681 as a diagnostic and therapeutic biomarker. These findings present new opportunities for understanding the molecular mechanisms underlying glioma and developing targeted treatments., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest related to the manuscript., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Brain aging is the leading risk factor for most neurodegenerative diseases and has been linked with high rates of neuron loss. Thus, identifying molecular mechanisms underlying neuron loss and pharmacological modulation may be of great importance for slowing or preventing age-related diseases. Herein, we investigated the roles of miR-92a, Akt, mTOR, and NF-κB in age-associated apoptosis in the hippocampus (a critical structure involved in brain aging) of male rats alone and in combination with prazosin. Twenty-four male Wistar rats were grouped into young control (3-month-old), aged (18-month-old), and aged + prazosin groups (n = 8 for each). Prazosin (1 mg/kg; i.p.) was administered for 4 weeks to aged rats. Apoptosis was detected by TUNEL staining. Western blot for Akt, mTOR, and NF-κB was conducted. miR-92a gene expression was performed by using RT-PCR. The results indicated a marked enhancement of apoptosis in the aging hippocampus. We also detected substantial up-regulation of NF-κB as well as substantial down-regulation of phosphorylated-Akt and mTOR in the aging hippocampus. Moreover, miR-92a gene expression was markedly reduced in the aging hippocampus. Treatment with prazosin significantly suppressed apoptosis and reversed miR-92a gene expression, as well as Akt, mTOR, and NF-κB protein expressions in the aging hippocampus. Considering the NF-κB regulatory role on miRNAs, our results suggest that NF-κB may be a negative transcriptional regulator of miR-92a, which in turn could regulate the Akt/mTOR signaling. In this regard, NF-κB upregulation may mediate the downregulation of miR-92a/Akt/mTOR axis, and thereby contribute to age-related neurodegeneration. This may provide a novel treatment target for delaying or preventing age-related problems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Silicosis is an occupational lung disease characterized by progressive pulmonary fibrosis, threatening millions of occupational workers worldwide due to a lack of effective treatments. To unveil mechanisms underlying silica-induced pulmonary fibrosis, we established in vitro and in vivo silicosis models, then employed scRNA-sequencing to profile the cellular landscape of lung tissues followed by characterization of macrophage pyroptosis and exosome therefrom in driving fibroblast-to-myofibroblast-transdifferentiation. Using hyperspectral imaging and artificial intelligence-powered pathological recognition, we found that silica nanoparticle (SiNP) triggered progressive lung fibrosis in vivo, and scRNA-seq implicated interstitial macrophage as pivotal regulators for fibroblast transdifferentiation. Mechanistically, SiNPs were demonstrated to induce macrophage pyroptosis and liberate exosomes, which upregulated pro-fibrotic markers and promoted myofibroblast transition. Subsequent high-throughput miR-sequencing revealed distinct exosomal miRNA signatures that modulated TGF-β signaling and induced fibroblast transdifferentiation. Lastly, we administered these exosomes into silicotic mice and found exacerbated inflammatory infiltration and pulmonary fibrosis. In conclusion, SiNPs exposure caused the remodeling of exosomal miRNAs by inducing interstitial macrophage pyroptosis, and exosomes derived from pyroptotic macrophage fuel fibroblast transdifferentiation by creating a pro-fibrotic microenvironment and promoting silicotic fibrosis. These findings provide critical insights into the pathogenesis of silicosis and the formulation of emerging therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

MicroRNA-222 (miR-222) plays a crucial role in neurodegeneration and is up-regulated in Alzheimer's disease (AD) patients. Andrographolide (Andro) has been reported to have anti-inflammatory and neuroprotective effects, showing potential for treating AD. The relationship between Andro's anti-AD mechanism and the regulation of miR-222 was discussed in this study. Andro protected against cytotoxicity induced by lipopolysaccharide (LPS) or amyloid-β, accompanied by upregulating p62 and Nrf2 mRNA and protein, downregulating TLR4 and NF-κBp65 mRNA and protein, and increasing LC3Ⅱ protein in vitro. miRNA and mRNA sequencing results showed that Andro downregulated miR-222 and upregulated sqstm1/p62. Andro was observed to inhibit the expression of miR-222 and the phosphorylation of NF-κBp65, while simultaneously enhancing the levels of p62 and LC3Ⅱ proteins, decreasing Aβ levels, and attenuating the release of inflammatory factors in the 3xTg-AD mice. MiR-222 mimic increased NF-κBp65 mRNA and protein levels in LPS-induced cells, while miR-222 inhibitors increased p62 mRNA and protein levels as well as Nrf2 and LC3Ⅱ protein, and decreased p-NF-κBp65 protein level in LPS-induced cells. Furthermore, miR-222 mimic reversed the increase in p62 and LC3Ⅱ protein and the decrease in NF-κBp65 mRNA and protein, as well as the decrease in Tau protein levels induced by Andro in LPS-induced cells. These findings suggest that Andro plays a neuroprotective role through downregulation of miR-222 to promote p62 expression while inhibiting NF-kB p65 expression, providing new insights into the mechanism of action of Andro for treating AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Maternal periconceptual nutrition affects the growth trajectory of developing fetuses by modulating gene expression. The regulatory mechanisms and their role in fetal development remain underexplored in livestock models. Herein, we investigated the effects of maternal rate of body weight (BW) gain during early gestation on the DNA methylation, microRNA profiles, and their interaction with the hepatic gene expression in female fetuses. At breeding, 36 crossbred beef heifers (∼13 months of age) were randomly assigned to a nutritional plane to gain Low (0.28 kg/day; LG, n = 18) or Moderate (0.79 kg/day; MG, n = 18) BW through the first 83 days of gestation. A subset of pregnant heifers (n = 17) was selected, and fetal liver samples were collected on day 83 of gestation for DNA methylation and miRNA-Sequencing. After data quality control, miRDeep2 and Bismark tools were used to analyze miRNA and methylation data, respectively. The bta-miR-206 was the only differentially expressed miRNA (FDR = 0.02). Eight differentially methylated genes were identified (DMGs, FDR < 0.1). The over-represented pathways and biological processes (adj. p < 0.05) for bta-miR-206 targeted genes were associated with embryonic development, energy metabolism, and mineral transport, whereas the DMGs regulated anatomical structural development and transcriptional regulation. Our results show that key genes involved with liver metabolism, tissue structure, and function were regulated by DNA methylation and the miR-206. However, further investigation is warranted to determine physiological responses and long-term consequences on animal performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mesenchymal stem cells (MSCs) have demonstrated promising therapeutic potential in the treatment of type 1 diabetes mellitus (T1DM); however, the underlying mechanism remains unclear. The primary pathological mechanism of T1DM involves activated T cells infiltrating the pancreas, leading to islet inflammation and the destruction of β-cells. However, the question of whether exosomes derived from MSCs can suppress the migration of T cells to the pancreas in the context of T1DM remains unresolved. In this study, we observed that miR-25 was highly expressed in MSCs exosomes and associated with signaling pathways related to cell migration. In vitro assay, we synthesized a miR-25 mimic and transiently transfected it into activated T cells, which revealed that miR-25 can effectively reduce the expression of CXCR3. Additionally, according to the in vivo T1DM mouse model, we found that there was a significant increase in miR-25 levels in T1DM mice treated with MSCs and the number of T cells decreased. Overall, our findings suggest that MSCs exosomes containing miR-25 can impede the infiltration of activated T cells into the pancreas in T1DM by repressing CXCR3 expression in these cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Understanding the essential role of miRNA in regulating cell invasion in glioblastoma opens up new avenues for targeted therapeutic interventions in the future. By screening out eligible miRNA expression data sets from the GEO database, the WGCNA package based on the R language is further used to construct a co-expression network model of the chip data set, to identify modules related to disease states and perform pivotal miRNA screening on the related modules. The target relationship between miRNA and TRPM8 was verified by bioinformatics and luciferase gene report, and the effect of miRNA overexpression on TRPM8 protein level was analyzed by Western blot. The result of miR-433 overexpression on the invasion ability of glioblastoma cells in vitro was examined by scratch test and Transwell invasion test. The results of this study indicate that the selected target miR-433 has a strong binding relationship with TRPM8 and can effectively regulate its expression. Furthermore, overexpression of miR-433 was found to inhibit the invasion ability of glioblastoma cells by targeting TRPM8. These data demonstrate that miR-433 can target TRPM8 to inhibit glioblastoma cell invasion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The ferroptosis of osteoblasts has been demonstrated to play a significant role in the development of steroid-induced osteonecrosis of the femoral head (SONFH). Additionally, microRNAs (miRNAs) have been identified as regulators of SONFH progression. However, the precise role of miRNAs in the regulation of osteoblast ferroptosis remains unclear. This study explored the role of exosomal miR-150-3p, derived from bone marrow mesenchymal stem cells (BMSCs), in osteoblast ferroptosis in SONFH. Dexamethasone (DEX) was used to treat osteoblasts to induce ferroptosis. BMSCs exosomes with different levels of miR-150-3p were introduced into a co-culture with the cells. To verify the targeting relationship between growth factor independence 1 (Gfi1) and the miR-150-3p promoter, as well as between miR-150-3p and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), respectively, chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and dual luciferase assays were employed. It was found that BMSCs-Exos-miR-150-3p mitigated DEX-triggered ferroptosis in osteoblasts. MiR-150-3p directly targeted BTRC, leading to its downregulation in osteoblasts. The BTRC/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was involved in the inhibition of DEX-induced osteoblast ferroptosis by BMSCs-Exos-miR-150-3p. Overexpression of BTRC reversed the inhibitory effect of BMSCs-Exos-miR-150-3p. In a SONFH rat model, BMSCs-Exos-miR-150-3p alleviated ferroptosis in osteoblasts through BTRC/Nrf2. In addition, Gfi1 bonded to the miR-150-3p promoter and inhibited its transcription. Gfi1 silencing elevated miR-150-3p levels and improves cell viability of BMSCs. In conclusion, our results suggest that BMSCs-Exos-miR-150-3p alleviates SONFH by suppressing ferroptosis through the regulation of BTRC/Nrf2 and miR-150-3p may be a potential target for SONFH treatment.

Motivated by studies showing an association between beta blocker (BB) use and positive bone outcomes, a pilot randomized control trial was performed at the Mayo Clinic which randomized postmenopausal women to placebo, propranolol (40 or 80 mg twice daily), atenolol (50 mg/d), or nebivolol (5 mg/d) to determine changes in bone turnover markers (BTMs) and in BMD over 20 wk. Pharmacogenetic effects and microRNA-mediated mechanisms involving beta adrenergic receptor and related genes have previously been found. We sought to validate these effects and discover new candidates in an ancillary study to the pilot clinical trial. We genotyped all participants and performed microRNA (miRNA) sequencing at baseline and at 20 wk for 24 participants from the atenolol or placebo groups. We discovered several variants in ADRB1, ADRB2, and HDAC4 which showed significant pharmacogenetic effects with BMD at multiple sites and with BTMs. Our miRNA results showed a significant treatment effect for miR-19a-3p over time with atenolol use in the low-responder group compared to placebo. Overall, the longitudinal miRNA analysis showed a large number of miRNAs which were up-regulated over the trial in the low responders but not the high responders compared to placebo, of which miR-19a-3p was one example. Finally, we compared the response to atenolol treatment for cardiovascular traits (pulse and blood pressure) with the response for the bone resorption marker, C-terminal telopeptide, and found a largely independent effect. Our results have implications for personalized therapy and for understanding mechanisms of BB treatment effect on bone., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The clinical syndrome appears as a dysregulated host response to infection that results in life-threatening organ dysfunction known as Sepsis. Sepsis is a serious public health concern where for every five deaths in ICU there is one patient who dies with sepsis worldwide. Sepsis is featured as unbalanced inflammation and immunosuppression which is sustained and profound, increasing patient susceptibility to secondary infections and mortality. microRNAs (miRNAs) play a central role in the control of many biological processes, and the deregulation of their expression has been linked to the development of oncological, cardiovascular, neurodegenerative, and metabolic diseases. In this review, we discuss the role of miRNAs in sepsis pathophysiology. Overall, miRNAs are seen as promising biomarkers, and it has been proposed to develop miRNA-based diagnosis and therapies for sepsis. Yet, the picture is not so straightforward because of miRNAs' versatile and dynamic features. More research is needed to clarify the expression and role of miRNAs in sepsis and promote the use of miRNAs for sepsis management. This study provides an extensive, current, and thorough analysis of the involvement of miRNAs in sepsis. Its purpose is to encourage future research in this area, as tiny miRNAs have the potential to be used for rapid diagnosis, prognosis, and treatment of sepsis., (© 2025 Wiley Periodicals LLC.)

Background: Ischemic stroke (IS) is known for its high incidence, disability, and mortality, and there is an urgent need to investigate the pathophysiological mechanisms and develop novel treatment strategies., Objectives: We aimed to investigate the mechanisms of the novel circMap2k1/miR-135b-5p/Pidd1 axis in the treatment of IS progression with fluoxetine., Methods: The middle cerebral artery occlusion (MCAO) model was done in adult male Sprague-Dawley (SD) rats and followed by fluoxetine treatment and the injection of adeno-associated virus (AAV)-sh-ctr and AAV-sh-circMap2k1 into the bilateral hippocampal tissues of rats. Dual-luciferase reporter gene assay was employed to confirm the binding between miR-135b-5p and Pidd1. Enzyme-linked immunosorbent assay was performed to measure the concentrations of the inflammatory factors TNF-α, IL-6, and IL-1β in the plasma. The role of circMap2k1 in cells was tested by overexpression of circMap2k1. Cell viability was assessed using Cell Counting Kit-8 assay, while apoptosis was measured by flow cytometry., Results: Knockdown of circMap2k1 enhanced the therapeutic and protective effect of fluoxetine on IS injury in rats. Dual-luciferase reporter gene assay confirmed the targeting of miR-135b-5p to Pidd1. Additionally, fluoxetine deactivated the adsorption of miR-135b-5p by downregulating circMap2k1, and miR-135b-5p further exerted its inhibitory effect on Pidd1 and finally attenuated the inflammatory response caused by microglial polarization after IS. Cell experiments revealed that overexpression of circMap2k1 repressed cell viability and promoted cell apoptosis., Conclusions: Fluoxetine downregulated of circMap2k1 was associated ameliorate neurological injury and inflammatory responses induced by microglial polarization after IS. The manuscript is available as a preprint at this link: doi.org/10.21203/rs.3.rs-3209057/v1., (© 2025 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Aims: The aims of this study, using a porcine model of multiple trauma, were to investigate the expression of microRNAs at the fracture site, in the fracture haematoma (fxH) and in the fractured bone, compared with a remote unfractured long bone, to characterize the patterns of expression of circulating microRNAs in plasma, and identify and validate messenger RNA (mRNA) targets of the microRNAs., Methods: Two multiple trauma treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). For this study, fxH, fractured bone, unfractured control bone, plasma, lung, and liver samples were harvested. MicroRNAs were analyzed using quantitative real-time polymerase chain reaction arrays, and the identified mRNA targets were validated in vivo in the bone, fxH, lung, and liver tissue., Results: MicroRNA expression was associated with the trauma treatment strategy and differed depending on the type of sample. In the ETC group, a more advanced fracture healing response, as reflected by the expression of osteogenic microRNAs, was seen compared with the DCO group. DCO treatment resulted in a more balanced immune response in the systemic circulation as represented by significant upregulations of several anti-inflammatory microRNAs. The in vivo validation of the abundance of putative mRNA targets reflected the levels of microRNAs which were identified., Conclusion: Local and systemic microRNA patterns of expression were identified, specific for the treatment strategy in multiple trauma, which corresponded with the expression of mRNA at the fracture site and in target organs. These findings match clinical observations and offer insights into the cellular communication which may underlie the effects of using different surgical strategies in patients with multiple trauma, both locally and systemically. We also identified a systemic involvement of microRNAs in multiple trauma which may include distant cellular communication between injured tissues. Further research may further describe the temporospatial role of circulating microRNAs after multiple trauma, their potential role in communication between organs, and prospective therapeutic applications., Competing Interests: R. V. M. Groven, J. Greven, M. Huber-Lang, and F. Hildebrand report funding from the German Research Foundation (429837092), related to this study. M. Huber-Lang reports consulting fees from Stryker and Gloryen, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from CLS Behring, all of which are unrelated to this study. M. van Griensven reports grants or contracts from EU H2020 and Health Holland, royalties or licenses from Elsevier, support for attending meetings and/or travel from EORS, and a planned patent for an immunologic testing device., (© 2025 The British Editorial Society of Bone & Joint Surgery.)

We reported that an acquired miR-142 deficit transforms chronic phase (CP) chronic myeloid leukemia (CML) leukemic stem cells (LSCs) into blast crisis (BC) LSCs. Given the role of miR-142 in the development and activity of the immune system, we postulated that this deficit also promotes LSC immune escape. Herein, we report on IL-6-driven miR-142 deficit occurring in T cells during BC transformation. In CML murine models, miR-142 deficit impairs thymic differentiation of lymphoid-primed multipotent progenitors (LMPP) into T cells and prevents T cells' metabolic reprogramming, thereby leading to loss of T cells and leukemia immune escape. Correcting miR-142 deficit with a miR-142 mimic compound (M-miR-142), alone or in combination with immune checkpoint antibodies, restores T cell number and immune activity, leading to LSC elimination and prolonged survival of BC CML murine and patient-derived xenograft models. These observations may open new therapeutic opportunities for BC CML and other myeloid malignancies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

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.)

Background: Amplified imaging of microRNA (miRNA) in cancer cells is essential for understanding of the underlying pathological process. Synthetic catalytic DNA circuits represent pivotal tools for miRNA imaging. However, most existing catalytic DNA circuits can not achieve the reactant recycling operation in cells and in vivo. Additionally, specificity miRNA imaging in tumor site also is a challenge. Herein, inspired by "turning waste into wealth", we report a DNA sensor for imaging of miRNA in target cells based on apurinic/apyrimidinic endonuclease 1 (APE1)-activated reactant recycling catalytic DNA circuit., Results: The sensing function of the DNA sensor is suppressed firstly through engineering an apurinic/apyrimidinic (AP) site. In the presence of APE1, the AP site undergoes hydrolysis, thereby activating sensing activity and triggering the strand displacement reaction (SDR) under miRNA assistance. In this catalytic DNA circuit, the next reaction cycle can be initiated when the duplex strand waste products are reverted into active components, which allows it to be performed continuously just consuming fuel DNA without depleting the reactant. Noteworthy, the liposome plays important role in overcome biological barriers for nucleic acid delivery. The amplified miRNA imaging strategy is carried out in vivo by this DNA sensor with reducing off-tumor signal under assistance with APE1, and enhances tumor-to-normal tissue contrast compared with traditional catalytic DNA circuit., Significance and Novelty: Firstly, APE1-activated reactant recycling catalytic DNA circuit is developed. Secondly, miRNA image in cell and in animal is achieved with high spatial selectivity. Thirdly, the signal-to-background ratio for imaging is improved in vitro and in vivo. Lastly, our strategy provides an automatic yet versatile approach for the development of more efficient and selective DNA circuits capable of differentiating miRNA in cancer cells from those in normal cells, promising to be valuable in cancer diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Metabolic associated fatty liver disease (MAFLD), previously defined as non-alcoholic fatty liver disease (NAFLD), has been shown to be closely related to many environmental pollutants. Lately, we found methyl tert-butyl ether (MTBE), a new environmental pollutant, could increase NAFLD risk in American adults, which still needs more population epidemiological studies to verify, and its pathogenic mechanism is not yet clear., Methods: We conducted a cross-sectional study among petrol station workers, diagnosed their MAFLD according to internationally recognised diagnostic criteria, assessed the potential association of MTBE exposure with MAFLD risk, and explored the miR-18a-5p/PXR/SREBP2 pathway as possible pathogenic mechanisms in male Wistar rats and HepaRG cells treated with MTBE., Results: Blood MTBE levels were found to be significantly correlated with an increased risk of MAFLD, and MAFLD risk increased by 24.3% for every 0.1 μg/L increase in blood MTBE. Consistently, we found that MTBE exposure could induce MAFLD in rats and HepaRG cells, and activate pregnane X receptor (PXR) by inhibiting miR-18a-5p to upregulate the expression of sterol regulatory element-binding protein 2 (SREBP2) and its nuclear translocation, thereby upregulating the expression of its downstream target genes., Conclusions: Our study demonstrated that MTBE exposure might be a significant risk factor for MAFLD, and MTBE could promote liver cholesterol synthesis and lipid deposition by activating the miRNA-18a-5p/PXR/SREBP2 pathway., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Current diagnostic biomarkers for acute myocardial infarction (AMI), such as troponins, often lack specificity, leading to false positives under non-cardiac conditions. Recent studies have implicated circadian rhythm and immune infiltration in the pathogenesis of AMI. This study hypothesizes that analyzing the interplay between circadian rhythm-related gene expression and immune infiltration identify highly specific diagnostic biomarkers for AMI. Our results demonstrated differential expression of 15 circadian rhythm-related genes (CRGs) between AMI patients and healthy individuals, with five key genes-JUN, NAMPT, S100A8, SERPINA1, and VCAN identified as key contributors to this process. Functional enrichment analyses suggest these genes significantly influence cytokine and chemokine production in immune responses. Immune infiltration assessments using ssGSEA indicated elevated levels of neutrophils, macrophages, and eosinophils in AMI patients. Additionally, we identified potential therapeutic implications with 13 pivotal miRNAs and 10 candidate drugs targeting these genes. The Benjamini-Hochberg method was employed to adjust for multiple testing, and the results retained statistical significance. RT-qPCR analysis further confirmed the upregulation of these five genes under hypoxic conditions, compared to controls. Collectively, our findings highlight the critical role of CRGs in AMI, providing a foundation for improved diagnostic approaches and novel therapeutic targets., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Growing research reveals that circular RNAs (circRNAs) play a major part in the progression and development of cancer. Here, we investigated the oncogenic function and regulatory mechanisms of the circRNA circACTN4 in hepatocellular carcinoma (HCC), particularly in the tumor epithelial-mesenchymal transition (EMT). In vitro functional assays (Cell Counting Kit 8, TUNEL, scratch wound healing, and invasion assays) of HCC cell lines, alongside in vivo analyses of subcutaneous tumors in nude model mice, were employed to assess the impact of circACTN4 on HCC proliferation. Interactions concerning circACTN4, microRNA (miR)-424-5p, and non-SMC condensing I complex subunit G (NCAPG) have been assessed deploying luciferase reporter assays and also quantitative reverse transcription PCR investigation of circACTN4 transcripts in HCC tissues. Findings indicated a high expression of circACTN4 in HCC, promoted proliferation, while inhibiting apoptosis of HCC cells, and correlated with poor prognosis. Mechanistically, circACTN4 served as a rival internal RNA for miR-424 5p, controlling NCAPG level and initiating the Wnt/β-catenin signaling routes, which in turn impacted the EMT machinery in HCC. According to our surveys, the circACTN4/miR-424 5p/NCAPG axis could be an intriguing candidate for therapy to address the treatment of HCC., Competing Interests: Declarations. Conflicts of interest: The authors declare no competing interests. Ethics approval and consent to participate: This study complied with the standards of the 1975 Declaration of Helsinki, and the experiments were approved by the Ethics Committee of Affiliated Hospital of Youjiang Medical University for Nationalities (Approval no. YYFY-LL-2018–112). Written informed consent was obtained from patients who provided samples. The animal experiments were approved by the institutional ethics committee of Youjiang Medical University for Nationalities, Guangxi, China(Approval no. 2024042601)., (© 2025. The Author(s).)

Atherosclerosis (AS) is a chronic disease initiated by vascular endothelial dysfunction, with low shear stress (SS) being a critical inducing factor in this dysfunction. Apoptosis, a form of programmed cell death, is closely associated with AS progression. However, the impact of low SS on endothelial apoptosis and its specific molecular mechanisms remains unclear. Our study revealed that low SS induces apoptosis in endothelial cells and contributes to endothelial dysfunction. Under low SS conditions, miR-330 expression was markedly upregulated, which subsequently targeted and inhibited SOD2 expression, leading to ROS accumulation and oxidative stress. Overexpression of SOD2 under low SS conditions markedly elevated HSP70 expression, contributing to endothelial homeostasis. However, when HSP70 expression was inhibited in the context of SOD2 overexpression, there was a significant increase in pro-apoptotic proteins (BAX and cleaved-caspase-3) and total apoptosis rate, along with a significant reduction in endothelial function markers such as nitric oxide and endothelial nitric oxide synthase. Notably, our experiments indicated no direct interaction between SOD2 and HSP70. Furthermore, inhibiting ROS production significantly raised HSP70 expression, suggesting that SOD2 regulates HSP70 in an indirect process involving ROS. In summary, our findings elucidate that low SS induces endothelial apoptosis and dysfunction through the miR-330/SOD2/HSP70 signaling pathway, providing valuable insights into AS intervention and prevention., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and grave malignancies with confined and ineffective therapeutic options. XPO1 is a critical regulator of nuclear export and activation of tumor suppressor proteins. The present study evaluated the therapeutic potential and molecular mechanisms of XPO1 inhibition against PDAC. Firstly, we observed significant overexpression of XPO1 transcript in 179 PDAC patients than 171 normal pancreatic tissues in TCGA transcriptomic dataset. Higher XPO1 transcript levels displayed worse overall and disease-free survival. Further, we confirmed significant upregulation of XPO1 in a panel of PDAC cells. Eltanexor treatment resulted in significant inhibition of cell viability, clonogenic growth, migration, and epithelial-mesenchymal transition (EMT), along with the induction of cell cycle arrest. Mechanistically, eltanexor modulated the expression of key proteins including p21, p27, p53, cyclin B1, cyclin D1, c-Myc, N-cadherin, vimentin, E-cadherin associated with the cell viability, growth, cell cycle and EMT. Additionally, the eltanexor treatment resulted in marked increase in expression of γH2AX, and cleaved PARP, cleaved caspase-9 leading to induction of DNA damage and apoptosis of PDAC cells, respectively. Moreover, eltanexor treatment regulated the expression of key non-coding RNAs including miR193b, DINO, MALAT-1, H19, and SOX21-AS1 linked with tumorigenesis. Our results revealed a correlation among miR193b/KRAS/LAMC2, XPO1/KRAS, and LAMC2/KRAS. The findings also revealed that eltanexor treatment rescued the expression of miR193b which acts as a sponge for LAMC2 and KRAS resulting in the suppression of AKT/ERK downstream signaling cascade in PDAC. Interestingly, the combination of eltanexor with gemcitabine showed significant anticancer activity in PDAC cells. Altogether, our findings revealed the crucial role of XPO1 in modulating the expression of oncogenic proteins, ncRNAs, and DNA damage during PDAC progression as well as identified novel therapeutic miR-193b/KRAS/LAMC2/ERK/AKT axis., Competing Interests: Declaration of competing interest The authors have declared no competing or financial interests., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Medullary thyroid cancer (MTC) is a highly aggressive and chemotherapy-resistant cancer originating from the thyroid's parafollicular C cells. Due to its resistance to conventional treatments, alternative therapies such as boric acid have been explored. Boric acid, a boron-based compound, has shown anticarcinogenic effects, positioning it as a potential treatment option for MTC. TT medullary thyroid carcinoma cell line (TT cells) and human thyroid fibroblast (HThF cells) were utilized for the cell culture experiments. Cell viability was assessed using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. Total RNA was extracted using Trizol reagent for gene expression and microRNA (miRNA) analysis via reverse transcription-polymerase chain reaction (RT-PCR). The extent of apoptosis induced by boric acid was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Colony formation assays were conducted to evaluate the impact of boric acid on the colony-forming ability of MTC cells. At 48 h, 50% inhibitory concentration (IC50) of boric acid was found to be 35 μM. Treatment with boric acid resulted in significant modulation of apoptosis-related genes and miRNAs, including increased expression of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), apoptotic protease activating factor 1 (APAF-1), Bcl-2-associated X protein (Bax), caspase-3, and caspase-9. In contrast, the expression of B cell lymphoma 2 (Bcl2), B cell lymphoma- extra-large (Bcl-xl), and microRNA-21 (miR-21), which are linked to the aggressiveness of MTC, was significantly reduced. The TUNEL assay indicated a 14% apoptosis rate, and there was a 67.9% reduction in colony formation, as shown by the colony formation assay. Our study suggests that boric acid may have anticancer activity in MTC by modulating apoptotic pathways. These findings suggest that boric acid could be a potential therapeutic agent for MTC and possibly for other malignancies with similar pathogenic mechanisms., Competing Interests: Declarations. Ethics Approval: TT (ATCC, CRL 1803TM) and HThF (ScienCell Cat No: 3730) cell lines, which provide de-identified samples ,were used in this study,. This study was reviewed and deemed exempt by our Pamukkale Univercity Institutional Review Board. The BioBank protocols are in accordance with the ethical standards of our institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s).)

This study aims to explore the molecular mechanisms of miR-206-3p in regulating Hsp90aa1 and its involvement in the central nervous system (CNS) injury in heat stroke. Weighted gene co-expression network analysis (WGCNA) was performed on the GSE64778 dataset of heat stroke to identify module genes most closely associated with disease characteristics. Through the selection of key genes and predicting upstream miRNAs using RNAInter and miRWalk databases, the regulatory relationship between miR-206-3p and Hsp90aa1 was determined. Through in vitro experiments, various methods, including bioinformatics analysis, dual-luciferase reporter gene assay, RIP experiment, and RNA pull-down experiment, were utilized to validate this regulatory relationship. Furthermore, functional experiments, including CCK-8 assay to test neuron cell viability and flow cytometry to assess neuron apoptosis levels, confirmed the role of miR-206-3p. Transmission electron microscopy, real-time quantitative PCR, DCFH-DA staining, and ATP assay were employed to verify neuronal mitochondrial damage. Heat stroke rat models were constructed, and mNSS scoring and cresyl violet staining were utilized to assess neural functional impairment. Biochemical experiments were conducted to evaluate inflammation, brain water content, and histopathological changes in brain tissue using H&E staining. TUNEL staining was applied to detect neuronal apoptosis in brain tissue. RT-qPCR and Western blot were performed to measure gene and protein expression levels, further validating the regulatory relationship in vivo. Bioinformatics analysis indicated that miR-206-3p regulation of Hsp90aa1 may be involved in CNS injury in heat stroke. In vivo, animal experiments demonstrated that miR-206-3p and Hsp90aa1 co-localized in neurons of the rat hippocampal CA3 region, and with prolonged heat stress, the expression of miR-206-3p gradually increased while the expression of Hsp90aa1 gradually decreased. Further in vitro cellular mechanism validation and functional experiments confirmed that miR-206-3p could inhibit neuronal cell viability and promote apoptosis and mitochondrial damage by targeting Hsp90aa1. In vivo, experiments confirmed that miR-206-3p promotes CNS injury in heat stroke. This study revealed the regulatory relationship between miR-206-3p and Hsp90aa1, suggesting that miR-206-3p could regulate the expression of Hsp90aa1, inhibit neuronal cell viability, and promote apoptosis, thereby contributing to CNS injury in heat stroke., Competing Interests: Declarations. Ethics Approval and Consent to Participate: All animal experiments have received approval from the Ethics Committee of the First People’s Hospital of Nantong City (luncheon review no. 2021KT007) and adhered to the principles of experimental animal management and use in accordance with academic rigor. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, 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&#95;0082374 on NSCLC progression. Levels of circ&#95;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&#95;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&#95;0082374 was a stable circRNA with high expression in NSCLC tissues and cells. Functionally, circ&#95;0082374 silencing suppressed NSCLC cell proliferation and metastasis. Moreover, its down-regulation enhanced ferroptosis by decreasing iron and lipid peroxidation accumulation. Mechanistically, circ&#95;0082374 could indirectly up-regulate GPX4 expression via miR-491-5p, indicating the circ&#95;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&#95;0082374 exerted on NSCLC cells. Moreover, knockdown of circ&#95;0082374 impeded NSCLC growth and EMT via regulating miR-491-5p and GPX4. Circ&#95;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.)

This study was dedicated to investigating the effects of microRNA-128-3p (miR-128-3p) on neuronal apoptosis and neurobehavior in cerebral palsy (CP) rats via the Smurf2/YY1 axis.In vivo modeling of hypoxic-ischemic (HI) CP was established in neonatal rats. Neurobehavioral tests (geotaxis reflex, cliff avoidance reaction, and grip test) were measured after HI induction. The HI-induced neurological injury was evaluated by HE staining, Nissl staining, TUNEL staining, immunohistochemical staining, and RT-qPCR. The expression of miR-128-3p, Smurf2, and YY1 was determined by RT-qPCR and western blot techniques. Moreover, primary cortical neurons were used to establish the oxygen and glucose deprivation (OGD) model in vitro, cell viability was detected by CCK-8 assay, neuronal apoptosis was assessed by flow cytometry and western blot, and the underlying mechanism between miR-128-3p, Smurf2 and YY1 was verified by bioinformatics analysis, dual luciferase reporter assay, RIP, Co-IP, ubiquitination assay, western blot, and RT-qPCR.In vivo, miR-128-3p and YY1 expression was elevated, and Smurf2 expression was decreased in brain tissues of hypoxic-ischemic CP rats. Downregulation of miR-128-3p or overexpression of Smurf2 improved neurobehavioral performance, reduced neuronal apoptosis, and elevated Nestin and NGF expression in hypoxic-ischemic CP rats, and downregulation of Smurf2 reversed the effects of downregulation of miR-128-3p on neurobehavioral performance, neuronal apoptosis, and Nestin and NGF expression in hypoxic-ischemic CP rats, while overexpression of YY1 reversed the effects of Smurf2 on neurobehavioral performance, neuronal apoptosis, and Nestin and NGF expression in hypoxic-ischemic CP rats. In vitro, downregulation of miR-128-3p effectively promoted the neuronal survival, reduced the apoptosis rate, and decreased caspase3 protein expression after OGD, and overexpression of YY1 reversed the ameliorative effect of downregulation of miR-128-3p on OGD-induced neuronal injury. miR-128-3p targeted to suppress Smurf2 to lower YY1 ubiquitination degradation and decrease its expression.Inhibition of miR-128-3p improves neuronal apoptosis and neurobehavioral changes in hypoxic-ischemic CP rats by promoting Smurf2 to promote YY1 ubiquitination degradation and reduce YY1 expression., Competing Interests: Declarations. Ethics Approval: The animal care procedures and animal experiments in the research were conducted under the ratification of the Animal Ethics Committee of Shanxi Provincial People’s Hospital (approval number: 20210415), and the handling of animals during the experiment was conducted in strict accordance with international ethical guidelines and national health guidelines regarding the maintenance and use of laboratory animals. Competing Interests: The authors declare no competing interests., (© 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.)

The role of circular RNAs (circRNAs) in sepsis-induced lung injury is not clear. This study investigated the role and molecular mechanism of a novel circRNA in sepsis-induced lung injury and explored its prognostic value in patients with sepsis. In this study, aberrant circRNA expression profiling in lung tissues from mice with sepsis-induced lung injury was analyzed using high-throughput sequencing. circRNA-Cacna1d was verified by qRT-PCR, and its biological function in sepsis-induced lung injury was validated in vitro and in vivo . The interactions among circRNA-Cacna1d, microRNAs (miRNAs), and their downstream genes were verified. Furthermore, the clinical value of circRNA-Cacna1d in peripheral blood from patients with sepsis was also evaluated. We found that circRNA-Cacna1d expression was significantly increased in lung tissues of mice with sepsis and in microvascular endothelial cells after LPS challenge. circRNA-Cacna1d knockdown alleviated inflammatory response and ameliorated the permeability of vascular endothelium, thereby mitigating sepsis-induced lung injury and significantly improving the survival rate of mice with sepsis. Mechanistically, circRNA-Cacna1d directly interacted with miRNA-185-5p and functioned as a miRNA sponge to regulate the RhoA/ROCK1 signaling pathway. The expression level of circRNA-Cacna1d in patients with early sepsis was significantly higher than that in the healthy control subjects. Higher levels of circRNA-Cacna1d in patients with sepsis were associated with increased disease severity and poorer outcomes. In conclusions, circRNA-Cacna1d may play a role in sepsis-induced lung injury by regulating the RhoA/ROCK1 axis by acting as a miRNA-185-5p sponge. circRNA-Cacna1d is a potential therapeutic target for sepsis-induced lung injury and a prognostic biomarker in sepsis.

Epidemiology has shown a strong relationship between fine particulate matter (PM) exposure and cardiovascular disease. However, it remains unknown whether PM aggravates myocardial ischemia-reperfusion (I/R) injury, and the related mechanisms are unclear. Our previous study has shown that adipose stem cell-derived exosomes (ADSC-Exos) contain high levels of Mir221 and Mir222 . The present study investigated the effects of PM exposure on I/R-induced cardiac injury through mitophagy and apoptosis, as well as the potential role of Mir221 and Mir222 in ADSC-Exos. Wild-type, mir221- and mir222- knockout (KO), and Mir221- and Mir222- overexpressing transgenic (TG) mice were intratracheally injected with PM (10 mg/kg). After 24 h, mice underwent left coronary artery ligation for 30 min, followed by 3 h of reperfusion (I/R). H9c2 cardiomyocytes were cultured under 1% O 2 for 6 h, then reoxygenated for 12 h (hypoxia-reoxygenation [H/R]). PM aggravated I/R (or H/R) cardiac injury by increasing ROS levels and causing mitochondrial dysfunction, which increased the expression of mitochondrial fission-related proteins (DNM1L/Drp1 and MFF) and mitophagy-related proteins (BNIP3 and MAP1LC3B/LC3B) in vivo and in vitro . Treatment with ADSC-Exos or Mir221- and Mir222- mimics significantly reduced PM+I/R-induced cardiac injury. Importantly, ADSC-Exos contain Mir221 and Mir222 , which directly targets BNIP3, MAP1LC3B/LC3B, and BBC3/PUMA, decreasing their expression and ultimately reducing cardiomyocyte mitophagy and apoptosis. The present data showed that ADSC-Exos treatment regulated mitophagy and apoptosis through the Mir221 and Mir222 -BNIP3-MAP1LC3B-BBC3/PUMA pathway and significantly reduced the cardiac damage caused by PM+I/R. The present study revealed the novel therapeutic potential of ADSC-Exos in alleviating PM-induced exacerbation of myocardial I/R injury. Abbreviation: ADSC-Exos: adipose-derived stem cell exosomes; AL: autolysosome; ATP: adenosine triphosphate; BBC3/PUMA: BCL2 binding component 3; BNIP3: BCL2/adenovirus E1B interacting protein 3; CASP3: caspase 3; CASP9: caspase 9; CDKN1B/p27: cyclin dependent kinase inhibitor 1B; CVD: cardiovascular disease; DCFH-DA: 2',7'-dichlorodihydrofluorescein diacetate; DHE: dihydroethidium; DNM1L/Drp1: dynamin 1-like; EF: ejection fraction; FS: fractional shortening; H/R: hypoxia-reoxygenation; I/R: ischemia-reperfusion; LDH: lactate dehydrogenase; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFF: mitochondrial fission factor; miRNA: microRNA; NAC: N-acetylcysteine; OCR: oxygen consumption rate; PIK3C3/Vps34: phosphatidylinositol 3-kinase catalytic subunit type 3; PM: particulate matter; PRKAA1/AMPK: protein kinase AMP-activated catalytic subunit alpha 1; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TRP53/p53: transformation related protein 53; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling.

Exercise is an effective way to alleviate breast cancer-induced cardiac injury to a certain extent. However, whether voluntary exercise (VE) activates cardiac signal transducer and activator of transcription 3 (STAT3) and the underlying mechanisms remain unclear. This study investigated the role of STAT3-microRNA(miRNA)-targeted protein axis in VE against breast cancer-induced cardiac injury.VE for 4 weeks not only improved cardiac function of transgenic breast cancer female mice [mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT +)] compared with littermate mice with no cancer (MMTV-PyMT -), but also increased myocardial STAT3 tyrosine 705 phosphorylation. Significantly more obvious cardiac fibrosis, smaller cardiomyocyte size, lower cell viability, and higher serum tumor necrosis factor (TNF)-α were shown in MMTV-PyMT + mice compared with MMTV-PyMT - mice, which were ameliorated by VE. However, VE did not influence the tumor growth. MiRNA sequencing identified that miR-181a-5p was upregulated and miR-130b-3p was downregulated in VE induced-cardioprotection. Myocardial injection of Adeno-associated virus serotype 9 driving STAT3 tyrosine 705 mutations abolished cardioprotective effects above. Myocardial STAT3 was identified as the transcription factor binding the promoters of pri-miR-181a (the precursor of miR-181a-5p) and HOX transcript antisense RNA (HOTAIR, sponged miR-130b-3p) in isolated cardiomyocytes. Furthermore, miR-181a-5p targeting PTEN and miR-130b-3p targeting Zinc finger and BTB domain containing protein 20 (Zbtb20) were proved in AC-16 cells. These findings indicated that VE protects against breast cancer-induced cardiac injury via activating STAT3 to promote miR-181a-5p targeting PTEN and to promote HOTAIR to sponge miR-130b-3p targeting Zbtb20, helping to develop new targets in exercise therapy for breast cancer-induced cardiac injury., Competing Interests: Declarations. Conflict of interest: The authors have no conflict of interest., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background & Aims: Liver fibrosis and its end-stage form cirrhosis contribute to millions of deaths annually. The lack of robust antifibrotic molecules is in part attributed to the absence of any functional screens to identify molecular regulators using patient-derived primary human hepatic myofibroblasts, which are key drivers of fibrosis., Methods: Here, to identify robust regulators of fibrosis, we performed functional microRNA screenings in primary human hepatic myofibroblasts followed by in vivo validation in three independent mouse models of fibrosis (toxin, cholestasis and MASH)., Results: We identified miR-190b-5p and miR-296-3p as robust antifibrotic miRNAs that suppress liver fibrosis. Notably, the expression of miR-190b-5p and miR-296-3p was found to be significantly reduced in human livers with fibrosis. Mechanistically, we discovered hyaluronan synthase 2 (HAS2) and integrin alpha-6 (ITGA6) as novel targets of miR-190b-5p and miR-296-3p, respectively. Furthermore, we demonstrated that the antifibrotic properties of miR-190b-5p and miR-296-3p are, at least in part, dependent on HAS2 and ITGA6. Finally, we showed the antifibrotic function of both miRNAs in a human liver bud model, which mimics multiple features of the human liver., Conclusions: Collectively, in our study we discovered miR-190b-5p and miR-296-3p as two novel antifibrotic miRNAs, and that HAS2 and ITGA6 contribute to miR-190b-5p- and miR-296-3p-mediated inhibition of liver fibrosis. These results provide a foundation for future research to explore the clinical utility of miR-190b-5p and miR-296-3p in fibrosis., Impact and Implications: Liver fibrosis and cirrhosis contribute to millions of deaths worldwide and remain unmet medical needs. In this study, we discovered two microRNAs, miR-190b-5p and miR-296-3p, which suppress liver fibrosis in preclinical mouse models and a human liver bud model. Our promising results encourage further studies that aim to develop both miRNAs for the treatment of liver fibrosis in patients., Competing Interests: Conflict of interest Authors declare no conflict of interest related to this study. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Gestational diabetes is marked impaired glucose tolerance, poses various adverse outcomes including increased BMI and obesity. These outcomes results from excess lipid accumulation which is marked by elevated triglycerides. In GDM, placenta exhibits altered lipid metabolism, including reduced fatty acid oxidation and increased triglyceride accumulation. These elevated triglycerides can also contribute to oxidative stress in GDM. SIRT7 plays an important role in regulating lipid metabolism and triglycerides levels. This study aimed to investigate the potential of miRNA to regulate the placental SIRT7 in GDM. PCR analysis reveals that SIRT7 expression along with oxidative stress markers elevated in GDM placenta. These elevated SIRT7 levels were positively correlated with BMI and triglycerides levels in GDM subjects. miR-125b-5p was identified to regulate SIRT7 mRNA using in-silico approaches. Expression levels of miR-125b-5p were found to be downregulated in GDM placenta and found to be negatively correlated with SIRT7 mRNA expression. To confirm the hypothesis BeWo cells were transfected with anti-miR-125b and miR-125b-mimic. Anti-miR overexpressed the SIRT7 expression where mimic dysregulated it. Additionally, overexpressing miR-125b-5p controlled the elevated SIRT7 caused by the exposure of high glucose in BeWo cells. Collectively this study indicated that miR-125b-5p may regulate lipid metabolism via SIRT7 contributing to GDM. These findings highlights the warrant of further research to develop the therapeutic approaches that target miR-125b-5p to reduce lipid accumulation and obesity in GDM., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Ramkumar KM reports was provided by SRM Institute of Science and Technology., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Esophageal cancer (ESCA) is a common tumor noted in the digestive tract, which is highly malignant due to unclear early symptoms and poor last‑stage treatment effects; its mortality rate is relatively high. MicroRNA (miR) and signal transducer and activator of transcription 3 (STAT3) are key components of cellular signaling pathways; their interaction forms a complex and intricate information network that controls several types of biological behaviors in the cells. In the tumor cell, these signal transduction pathways are abnormally active, indicating that the STAT3 signaling pathway mediated by miRs is involved in the progression of various cancer types. The present review introduces the biological characteristics of miR and STAT3 and their relationship with ESCA. It summarizes the regulation of ESCA by the miR and STAT3 signaling pathways and analyzes the effects of these pathways on proliferation, apoptosis, invasion, metastasis and immune escape of cancer cells, as well as the impact on patient survival and prognosis. The purpose of the present review is to assess the miR/STAT3 signaling pathway in ESCA, improve the understanding of the pathogenesis of ESCA and facilitate the identification of therapeutic targets for ESCA.

Studies have demonstrated that circular RNAs (circRNAs) exert an important regulatory function in the pathogenesis of various tumors. However, their role in gastric cancer (GC) is still not completely understood. In our study, the differentially expressed circRNAs in GC tissues and matched adjacent normal tissues were analyzed by utilizing gene chips GSE93541, GSE89143, and GSE78092. The expression of has&#95;circ&#95;0006608 (circPFKP), miR-346, and CAMD3 was analyzed through quantitative real-time polymerase chain reaction (qRT-PCR). The CCK-8 assay and Transwell assay were employed to detect the effect of circPFKP on the proliferation, migration, and invasion of gastric cancer cells. The mice xenograft assay was used to assess the function of circPFKP in vivo. The targeting relationship between circPFKP, miR-346, and CAMD3 was predicted by bioinformatics analysis and confirmed by the dual-luciferase reporter assay and RNA pull-down assay. Our results screened and verified that circPFKP was down-regulated in gastric cancer tissues and cells. Overexpression of circPFKP in GC cells can inhibit cell proliferation, migration, invasion, and tumor growth in vivo. Additionally, circPFKP has been shown to act as a sponge for miR-346 to modulate the expression of CAMD3. Finally, we demonstrated that overexpression of CAMD3 or miR-346 inhibitor significantly reversed the effects of si-circPFKP on the proliferation, migration, and invasion of gastric cancer cells. In conclusion, this study provided that circPFKP inhibits the progression of GC via the miR-346/CAMD3 axis, this may provide a noval biomarker for the diagnosis and treatment of GC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)