Explore the vast range of titles available.

Objectives Pulp regeneration brings big challenges for clinicians, and vascularization is considered as its determining factor. We previously accomplished pulp regeneration with autologous stem cells from deciduous teeth (SHED) aggregates implantation in teenager patients, however, the underlying mechanism needs to be clarified for regenerating pulp in adults. Serving as an important effector of mesenchymal stem cells (MSCs), exosomes have been reported to promote angiogenesis and tissue regeneration effectively. Here, we aimed to investigate the role of SHED aggregate‐derived exosomes (SA‐Exo) in the angiogenesis of pulp regeneration. Materials and Methods We extracted exosomes from SHED aggregates and utilized them in the pulp regeneration animal model. The pro‐angiogenetic effects of SA‐Exo on SHED and human umbilical vein endothelial cells (HUVECs) were evaluated. The related mechanisms were further investigated. Results We firstly found that SA‐Exo significantly improved pulp tissue regeneration and angiogenesis in vivo. Next, we found that SA‐Exo promoted SHED endothelial differentiation and enhanced the angiogenic ability of HUVECs, as indicated by the in vitro tube formation assay. Mechanistically, miR‐26a, which is enriched in SA‐Exo, improved angiogenesis both in SHED and HUVECs via regulating TGF‐β/SMAD2/3 signalling. Conclusions In summary, these data reveal that SA‐Exo shuttled miR‐26a promotes angiogenesis via TGF‐β/SMAD2/3 signalling contributing to SHED aggregate‐based pulp tissue regeneration. These novel insights into SA‐Exo may facilitate the development of new strategies for pulp regeneration. The underlying mechanisms of the SHED aggregate involved in pulp regeneration is revealed in this paper. SHED aggregate‐derived exosomes (SA‐Exo) shuttled miR‐26a promote SHED endothelial differentiation and enhance the angiogenic ability of HUVECs via TGF‐β/SMAD2/3 signalling, which contributing to angiogenesis in pulp tissue regeneration.

Background Inflammation often leads to the occurrence of chronic pain, and many miRNAs have been shown to play a key role in the development of inflammatory pain. However, whether miR‐26a‐5p relieves pain induced by inflammation and its possible mechanism are still unclear. Methods The complete Freund's adjuvant (CFA)‐induced inflammatory pain mouse model was employed. Intrathecal or subcutaneous injection of miR‐26a‐5p agomir was performed after modeling to study its antinociceptive effect and the comparison of different administration methods. Bioinformatics analysis of miRNAs was performed to study the downstream mechanisms of miR‐26a‐5p. HE staining, RT‐qPCR, Western blotting, and immunofluorescence were used for further validation. Results A single intrathecal and subcutaneous injection of miR‐26a‐5p both reversed mechanical hypersensitivity and thermal latency in the left hind paw of mice with CFA‐induced inflammatory pain. HE staining and immunofluorescence studies found that both administrations of miR‐26a‐5p alleviated inflammation in the periphery and spinal cord. Bioinformatics analysis and dual‐luciferase reporter gene analysis identified Wnt5a as a direct downstream target gene of miR‐26a‐5p. Wnt5a was mainly expressed in neurons and microglia in the spinal cord of mice with inflammatory pain. Intrathecal injection of miR‐26a‐5p could significantly reduce the expression level of Wnt5a and inhibit the downstream molecules of noncanonical Wnt signaling Camk2/NFAT, inhibiting the release of spinal cord inflammatory factors and alleviating the activation of microglia. In addition, miR‐26a‐5p could also inhibit lipopolysaccharide (LPS)‐stimulated BV2 cell inflammation in vitro through a noncanonical Wnt signaling pathway. Conclusions miR‐26a‐5p is a promising therapy for CFA‐induced inflammatory pain. Both intrathecal and subcutaneous injections provide relief for inflammatory pain. miR‐26a‐5p regulated noncanonical Wnt signaling to be involved in analgesia partly through antineuroinflammation, suggesting a pain‐alleviating effect via noncanonical Wnt signaling pathway in the CFA‐induced inflammatory pain model in vivo. miR‐26a‐5p regulated Wnt5a/CaMKII/NFAT, a noncanonical Wnt signaling, involved in analgesia partly through antineuroinflammation, suggesting a pain‐alleviating effect via noncanonical Wnt signaling pathway in CFA‐induced inflammatory pain model in vivo and vitro.

Aberrant sialylation profiles on the cell surface have been recognized for their potential diagnostic value in identifying the regulation of tumor properties in several cancers, including hepatocellular carcinoma (HCC). Recently, increasing evidence has suggested that the deregulation of microRNA (miRNA) is a common feature in human cancers. In this study, we found obvious upregulation of sialyltransferase ST3GAL6 both in HCC cell lines and in tissue samples. The altered expression of ST3GAL6 was found to correlate with cell proliferation, migration, and invasion ability in HCC. Further investigation showed that miR‐26a negatively regulated ST3GAL6, inducing the suppression of cell proliferation, migration, and invasion in vitro. Moreover, we identified the protein kinase B/mammalian target of rapamycin (Akt/mTOR) pathway as the target of ST3GAL6 based on Western blot analysis. Analysis of a xenograft mouse model showed that miR‐26a significantly reduced tumor growth by suppressing activation of the Akt/mTOR pathway by directly targeting ST3GAL6. In conclusion, these data indicate that ST3GAL6 promotes cell growth, migration, and invasion and mediates the effect of miR‐26a through the Akt/mTOR signaling pathway in HCC. ST3GAL6 mediates the effect of miR‐26a on cell growth, migration and invasion in HCC. Akt/mTOR signaling pathway is identified as the downstream target of ST3GAL6 involved in HCC.

Addressing the challenge of promoting directional axonal regeneration in a hostile astrocytic scar, which often impedes recovery following spinal cord injury (SCI), remains a daunting task. Cell transplantation is a promising strategy to facilitate nerve restoration in SCI. In this research, a pro‐regeneration system is developed, namely miR‐26a@SPIONs‐OECs, for olfactory ensheathing cells (OECs), a preferred choice for promoting nerve regeneration in SCI patients. These entities show high responsiveness to external magnetic fields (MF), leading to synergistic multimodal cues to enhance nerve regeneration. First, an MF stimulates miR‐26a@SPIONs‐OECs to release extracellular vesicles (EVs) rich in miR‐26a. This encourages axon growth by inhibiting PTEN and GSK‐3β signaling pathways in neurons. Second, miR‐26a@SPIONs‐OECs exhibit a tendency to migrate and orientate along the direction of the MF, thereby potentially facilitating neuronal reconnection through directional neurite elongation. Third, miR‐26a‐enriched EVs from miR‐26a@SPIONs‐OECs can interact with host astrocytes, thereby diminishing inhibitory cues for neurite growth. In a rat model of SCI, the miR‐26a@SPIONs‐OECs system led to significantly improved morphological and motor function recovery. In summary, the miR‐26a@SPIONS‐OECs pro‐regeneration system offers innovative insights into engineering exogenous cells with multiple additional cues, augmenting their efficacy for stimulating and guiding nerve regeneration within a hostile astrocytic scar in SCI.

Acute lung injury (ALI) is an adverse disease of the respiratory system, and one of its prevalent causes is sepsis induction. Cell pyroptosis facilitates the progression of ALI and lncRNAs play critical roles in ALI. Thus, this research seeks to investigate the specific mechanism of NEAT1 in sepsis‐ALI.BEAS‐2B cells were exposed to lipopolysaccharide (LPS) to construct a cell model of sepsis‐induced ALI. The gene and protein expression were assessed using qRT‐PCR and western blot. Cell viability was identified by CCK‐8. Cell death was discovered using PI staining. The secretion of IL‐1β and IL‐18 was examined using ELISA. The interconnections among NEAT1, miR‐26a‐5p, and ROCK1 were confirmed using starbase, luciferase assay, and RIP.LPS treatment augmented NEAT1 and ROCK1 levels while mitigating miR‐26a‐5p level in BEAS‐2B cells. Additionally, LPS treatment facilitated cell death and cell pyroptosis, whereas NEAT1 silencing could reverse these effects in BEAS‐2B cells. Mechanistically, NEAT1 positively mediated ROCK1 expression by targeting miR‐26a‐5p. Furthermore, miR‐26a‐5p inhibitor offset NEAT1 depletion‐mediated suppressive effects on cell death and cell pyroptosis. ROCK1 upregulation decreased the inhibitory impacts produced by miR‐26a‐5p overexpression on cell death and cell pyroptosis. Our outcomes demonstrated NEAT1 could reinforce LPS‐induced cell death and cell pyroptosis by repressing the miR‐26a‐5p/ROCK1 axis, thereby worsening ALI caused by sepsis. Our data indicated NEAT1, miR‐26a‐5p, and ROCK1 might be biomarkers and target genes for relieving sepsis‐induced ALI.

Disc degeneration is a common clinical condition in which damaged discs cause chronic pain; however, a laboratory diagnosis method for its detection is not available. As circulating miRNAs have potential as biomarkers, their application in disc degeneration has not been explored. Here, we prepared serum miRNAs from a mouse disc degeneration model and performed miRNA‐Seq and quantitative PCR to characterize disc degeneration–associated miRNAs. We identified three miRNAs, including miR‐26a‐5p, miR‐122‐5p and miR‐215‐5p, undergoing perturbation during the pathogenesis of disc degeneration. Specifically, the levels of miR‐26a‐5p in the serum demonstrated steady increases in the model of disc degeneration, compared with those in the pre‐injury samples of younger age or compared with normal controls of the same age but without disc degeneration, whereas the miRNAs miR‐122‐5p and miR‐215‐5p exhibited lower expression in post‐injury samples than in their counterparts without the surgery. Moreover, we found that miR‐26a‐5p targets Smad1 expression, and Smad1 negatively regulates Vegfa expression in disc cells, and thus, miR‐26a‐5p promotes disc degeneration. In summary, we established a method that consistently profiles circulating miRNAs and identified multiple miRNAs as promising biomarkers for disc degeneration, among which miR‐26a‐5p enhances VEGF expression during disc degeneration through targeting Smad1 signalling.

MicroRNAs (miRNAs/miRs) play key roles in cancer progression. Extensive research has revealed that miR-26a is abnormally expressed and functions as a tumor suppressor in numerous types of cancer. Thus, the present study was undertaken to investigate the regulatory role and potential mechanism of action of miR-26a in breast cancer. Furthermore, the present study aimed to examine the alterations in miR-26a expression and its effects on human breast cancer cells. Reverse transcription-quantitative PCR was conducted to assess the differences in miR-26a expression between human breast cancer and normal breast specimens. A Cell Counting Kit-8 assay and cloning experiments were used to detect cell proliferation and clone formation. Wound healing and Transwell assays were performed to examine cell migration and invasion. A luciferase activity experiment was utilized to validate the association between miR-26a and family with sequence similarity 98 member A (FAM98A). Western blotting was conducted to detect the protein expression levels of FAM98A, sonic hedgehog signaling molecule (SHH), smoothened, frizzled class receptor (SMO) and GLI family zinc finger 1 (GLI1). The results indicated that miR-26a expression was decreased in breast carcinoma tissues and cell lines. Moreover, overexpression of miR-26a significantly suppressed cell proliferation, clone formation ability and metastasis, and it sensitized breast cancer cells to docetaxel. It was demonstrated that miR-26a directly targeted FAM98A, and that FAM98A, SHH, SMO and GLI1 expression levels were decreased in cells transfected with miR-26a mimics. Collectively, the results of the present study suggested that miR-26a negatively regulated the expression of FAM98A, indicating that it may play a key role in the suppression of breast carcinogenesis.

Objective Mesenchymal stromal/stem cells have neuroprotective effects that limit damage to the retina, which is predominantly mediated by the released extracellular vesicles (EVs). This study aims to investigate the protective effect of adipose‐derived mesenchymal stem cell‐derived EVs (ADSC‐EVs) against pyroptosis of retinal ganglion cells (RGCs). Methods ADSC‐EVs were isolated and then characterized. Mouse primary RGCs exposed to high glucose (HG) were applied for in vitro experiments. miR‐26a‐5p expression in RGCs after ADSC‐EV treatment was determined by RT‐qPCR. Target relation between miR‐26a‐5p and histone deacetylase 4 (HDAC4) was identified by luciferase reporter assay. miR‐26a‐5p blockad and HDAC4 ectopic expression experiments were conducted to clarify their functions in the pyroptosis of RGCs. The pyroptosis‐associated protein GSDMD‐N, inflammatory factors, and cell death were further evaluated by western blot, ELISA, and LDH assays, respectively. Results Exposure to HG reduced RGC viability and increased cell death, GSDMD‐N protein level, and IL‐1β and IL‐18 levels, indicating pyroptosis induction. However, these HG‐caused alterations could be reversed by ADSC‐EVs. ADSC‐EVs transferred miR‐26a‐5p into RGCs where miR‐26a‐5p targeted HDAC4 to limit its expression and enhance histone H3 lysine 27 acetylation (H3K27ac) modification at the nuclear factor erythroid 2‐related factor 2 (Nrf2) promoter region. This effect contributed to increases in Nrf2 protein level and nuclear translocation. Importantly, decreased H3K27ac modification at the Nrf2 promoter region could partially abrogate the inhibiting effect of ADSC‐EVs on HG‐induced RGC pyroptosis. Conclusion Overall, our findings reveal the beneficial effects of ADSC‐EVs shuttling miR‐26a‐5p on HG‐induced RGCs and determine a potential mechanism responsible for pyroptosis. ADSC‐EVs carrying miR‐26a‐5p confer protection against RGC pyroptosis by targeting HDAC4 and activating H3K27ac‐dependent Nrf2 expression.

Objective This study intended to explore the regulatory functions of LINC00240 on nasopharyngeal carcinoma (NPC). Methods MiR‐26a‐5p inhibitor, mimic, and siLINC00240 were transfected into NPC cells. QRT‐PCR was employed to assess miR‐26a‐5p and LINC00240 expressions. The targeting relationship of LINC00240 and miR‐26a‐5p was analyzed through dual luciferase reporter and RNA immunoprecipitation assay. Cell counting kit‐8 assay, colony formation assay, flow cytometry assay, wound healing assay, Transwell assay and in vitro angiogenesis assay were adopted for the evaluation of the effects of LINC00240 or miR‐26a‐5p and LINC00240 on NPC cells regarding cell proliferation, apoptosis and cycle, migration, invasion, and angiogenesis. EZH2, cell cycle, and epithelial‐mesenchymal transition (EMT)‐related protein expression was tested through Western blot. Results LINC00240 had a high expression in NPC tissues and cell lines. Silenced LINC00240 significantly suppressed the 5‐8F and HK1 cell proliferation, invasion, migration, and angiogenesis, but raised cell apoptosis, and cells were blocked in G0/G1 phase. MiR‐26a‐5p was a target of LINC00240. MiR‐26a‐5p upregulation suppressed the NPC cell proliferation, migration, invasion, angiogenesis, N‐cadherin and EZH2 expression, while it elevated apoptosis and p21, p27 and E‐cadherin expressions, whereas miR‐26a‐5p downregulation performed conversely. LINC00240 knockdown partially offset the effects of miR‐26a‐5p downregulation on cell proliferation, migration, invasion, angiogenesis, apoptosis, and EZH2. Conclusion LINC00240 knockdown restrained cell proliferation, invasion, migration, and angiogenesis, while it advanced apoptosis via miR‐26a‐5p in NPC by EZH2 inhibition. LINC00240 is a newly discovered lncRNA proven to be abnormally modulated in diverse tumor diseases and can regulate the initiation and progression of various cancers. But its role in nasopharyngeal carcinoma (NPC) remains unclear. In the present study, silenced LINC00240 was found to significantly suppress NPC cell proliferation, invasion, migration, and angiogenesis while it induced cell apoptosis and cell cycle arrest in the G0/G1 phase. With the targeting relationship of LINC00240and miR‐26a‐5p verified, further investigations showed that miR‐26a‐5p downregulation promoted the NPC cell proliferation, migration, invasion, angiogenesis, and EZH2 while it inhibited apoptosis, which partially offset the effects of LINC00240 knockdown on the aspects above. In summary, LINC00240 knockdown restrained NPC cell progress via miR‐26a‐5p by EZH2 inhibition.

Background Gestational diabetes mellitus is a common public health problem, accompanied by complications for the mother and fetus. So, introducing new biomarkers to identify early diabetes is essential. As serum miRNAs are potentially appropriate markers, we investigated miR‐26a and miR‐26b expression levels in pregnant women with and without gestational diabetes. Method Demographic and clinical characteristics of 40 gestational diabetic patients and 40 healthy controls were assessed. The expression level of miR‐26a and miR‐26b microRNAs was measured by real‐time PCR. Statistical analysis was done with GraphPad Prism software (version 8.4.3). Result The findings of this study showed that the expression level of miR‐26a and miR‐26b increased in women with gestational diabetes compared with healthy pregnant women, but the increase in expression was only significant for miR‐26a (p < 0.05). Conclusion According to the statistical and ROC curves, we suggest miR‐26a as a potential biomarker for the early diagnosis of gestational diabetes mellitus.