ABSTRACT Animal experimental studies involving the Igaki-Tamai stent (ITS), a bioresorbable poly-l-lactic acid scaffold, in peripheral arteries are limited, and existing studies evaluated only short-term (3-month) outcomes. This study compared arterial responses associated with the ITS and bare metal stent (BMS) over 6 months using intravascular ultrasound (IVUS) analysis and evaluated feasibility in porcine iliac arteries. Four miniature pigs underwent stent implantation with the ITS in the right iliac artery and the BMS in the left iliac artery. Follow-up evaluations at 6, 12, and 24 weeks included angiographic and IVUS analyses to assess neointimal hyperplasia, percent area stenosis (%AS), and percent in-stent volume obstruction (%VO). Histological analysis was performed to evaluate tissue injury and inflammation scores. At 6 weeks, the neointimal area did not differ significantly between the ITS and BMS groups (8.49 ± 2.10 mm² vs 13.47 ± 6.67 mm², P = .205). However, the ITS group exhibited a significantly smaller neointimal area at 12 weeks (6.87 ± 1.15 mm² vs 20.65 ± 10.99 mm², P = .050) and 24 weeks (5.20 ± 0.85 mm² vs 22.32 ± 12.03 mm², P = .042). %AS and %VO were significantly lower in the ITS group at all follow-ups. The ITS group showed reduced tissue damage (injury score: 0.80 ± 0.430 vs 1.74 ± 0.908, P < .001) and inflammation (inflammation score: 1.25 ± 0.516 vs 1.67 ± 0.832, P < .001) compared with the BMS group. The ITS was associated with reduced vessel injury, lower inflammatory response, and favorable luminal remodeling over 6 months in healthy porcine iliac arteries.

ABSTRACT Decellularized blood vessels with low immunogenicity and excellent biocompatibility are promising for tissue engineering and clinical applications. However, current decellularization methods face limitations in cell removal efficiency, matrix preservation, and biosafety. This study optimized the Triton X-100/SDS (TX-100/SDS) decellularization method using ultrasound technology by systematically evaluating the effects of ultrasound power, temperature, and processing time on decellularization efficiency. The optimized method achieved a 72% reduction in nucleic acid residues at 100 W power while preserving matrix integrity and significantly reducing chemical reagent residues. Structural and biosafety evaluations confirmed that the optimized scaffolds met biological safety standards and demonstrated excellent stability, providing a strong foundation for developing high-performance decellularized vascular materials for clinical applications.

Endovascular aneurysm repair (EVAR) is a widely accepted treatment for aortic pathologies owing to its minimally invasive nature. However, long-term complications, such as stent graft migration and infection, remain unresolved, primarily due to the persistent presence of synthetic materials and limited tissue integration. This pilot study evaluated the feasibility of a novel tissue-engineered stent graft (TESG) combining a bioresorbable poly-L-lactic acid (PLLA) stent with decellularized porcine veins. The veins were processed using a sodium dodecyl sulfate and the Triton X-100 decellularization protocol. Histological and ultrastructural analyses confirmed effective cell removal while preserving extracellular matrix components. Quantitative deoxyribonucleic acid (DNA) analysis showed a > 97% reduction in DNA content. The TESGs were assembled by suturing the decellularized veins into bioresorbable PLLA stents and implanted into porcine iliac arteries (n = 3). Commercially available prosthetic grafts were used as control implants to evaluate differences in tissue responses. Graft patency and morphology were assessed at implantation and on postoperative day 14 using angiography and intravascular ultrasonography. All TESGs remained patent, with no evidence of thrombosis or aneurysmal changes. Histological analysis revealed early endothelialization and smooth muscle cell infiltration within the TESG wall, in contrast to the prosthetic graft controls, which lacked comparable cellular integration. This study demonstrated the short-term feasibility and biological compatibility of a fully bioresorbable TESG. Although long-term outcomes remain to be established, these results support further development of TESG to reduce late complications through improved tissue integration and avoidance of permanent synthetic materials.

ABSTRACT Objective Periodontal ligament stem cells (PDLSCs), undifferentiated mesenchymal cells with multipotent differentiation and self-renewal capacities, constitute the optimal MSC population for periodontal regeneration. This study sought to elucidate the effects of concentrated growth factor (CGF) on the osteogenic differentiation of PDLSCs and analyze the underlying mechanisms. Methods PDLSCs were isolated from the molars of patients with malocclusion and characterized by flow cytometry, osteogenic induction, lipogenic induction, ARS staining and ORO staining. PDLSCs were treated with osteogenic induction medium containing different concentrations of CGF. The osteogenic ability of CGF in PDLSCs was analyzed via ALP staining, ARS staining, and ALP activity assays. WNK1, RUNX2 and OPN were detected by RT-qPCR. WNK1, RUNX2, OPN, β-catenin, GSK3β and p-GSK3β were detected by WB. The role of CGF in PDLSC osteogenic differentiation through the Wnt pathway was verified. Results PDLSCs were successfully isolated and cultured in vitro. After CGF treatment, ALP activity, mineralization nodule formation, and the expression of RUNX2 and OPN in PDLSCs were increased, with 0.1 mg/mL CGF showing the best osteogenic differentiation ability. WNK1, β-catenin, and p-GSK3β/GSK3β were elevated. CGF activated the Wnt pathway through WNK1. The promoting effects of CGF on osteogenic differentiation of PDLSCs were partially reversed after inhibition of WNK1 and the Wnt pathway. Conclusion CGF promotes PDLSC osteogenic differentiation by activating the Wnt pathway through WNK1.

ABSTRACT MicroRNAs (miRNAs) can be transported to tumor cells through exosomes secreted by bone marrow mesenchymal stem cells (BMSC-Exos) and exert regulatory functions within cells. Here, we aim to investigate the functional mechanism of miR-29a-3p carried by BMSC-Exos in the treatment of NSCLC. Based on the miRNA/mRNA gene expression data in the UCSC dataset (1029 NSCLC and 110 normal samples), bioinformatics analysis predicted the expression levels of miR-29a-3p and DNMT3A in NSCLC samples and their association with prognosis. Exosomes were isolated from BMSCs and characterized. BMSC-Exos with expressed or knocked out miR-29a-3p were treated A549 cells, and their biological effects on cells were evaluated, including proliferation, migration, and apoptosis. Western blotting was employed to explore the involvement of DNMT3A and JAK2/STAT3 signaling pathways. Furthermore, the binding between miR-29a-3p and DNMT3A was verified through dual-luciferase reporter assay. Following transfection with miR-29a-3p mimic and DNMT3A overexpression vectors, their roles in the biological processes of NSCLC were analyzed. In NSCLC, decreased expression of miR-29a-3p or increased expression of DNMT3A was closely associated with poor prognosis. miR-29a-3p can be transferred from BMSCs to A549 cells via exosomes, thereby inhibiting cell proliferation and migration while promoting apoptosis. DNMT3A was identified as a target gene of miR-29a-3p. Mechanistically, miR-29a-3p upregulation led to decreased DNMT3A expression and impaired JAK2/STAT3 signaling pathway. Overall, this study demonstrated that BMSC-derived exosomal miR-29a-3p restrained NSCLC by reducing DNMT3A/JAK2/STAT3 axis. These findings may provide new insights for the development of NSCLC treatment strategies.

ABSTRACT Background Epilepsy is a common disease of the nervous system. Recent advances in epigenetics have revealed DNA methylation as a key mechanism in epilepsy pathogenesis, particularly through dysregulation of GABAergic signaling. Baicalein has been shown to have anticonvulsant and neuroprotective effects. However, its epigenetic regulatory effects on GABA receptor function remain unexplored. Methods The status epilepticus (SE) model was induced by lithium chloride-pilocarpine (LiCl-PILO) in Sprague-Dawley (SD) rats. The rats were divided into control group, epileptic SE group and baicalein intervention group. Morris water maze (MWM) test, Nissl staining, immunofluorescence and enzyme-linked immunosorbent assay (ELISA) were used to detect cognitive functions and neuronal damage. Online sites, chromatin immunoprecipitation (ChIP) and western blotting were used to identify DNA methyltransferase 1 (DNMT1)-mediated methylation of gamma-aminobutyric acid type A receptor subunit delta (GABRD) promoter region. Results Baicalein treatment significantly prolonged the latency of SE onset and seizure onset, and improved the development of epilepsy. Meanwhile, baicalein improved the cognitive impairment in rats induced by LiCl-PILO. After treatment with baicalein, a sustained elevation in the number of neurons and NeuN levels was observed, along with a decrease in the contents of tumor necrosis factor -alpha (TNF-α), interleukin-1β (IL-1β), and ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampus. Mechanistically, baicalein interacted with DNMT1 to suppress GABRD promoter region methylation, thus increasing GABRD protein level in the hippocampus of rats induced by LiCl-PILO. Conclusion This study identifies DNMT1/GABRD axis as a novel epigenetic target for epilepsy intervention. Baicalein’s ability to enhance tonic inhibition through demethylation of GABRD provides a groundbreaking strategy for drug-resistant epilepsy.

ABSTRACT This study delves into the rejuvenating effects of SS-31 on aged human Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs), focusing on its potential to restore their diminished osteogenic differentiation capacity, a critical issue in geriatric medicine and bone tissue engineering. SS-31 significantly improved mitochondrial function, increasing ATP production by 35% and reducing ROS levels by 40% in aged BM-MSCs. Osteogenic differentiation was enhanced, as evidenced by a 2.8-fold increase in ALP activity and a 3.5-fold increase in Alizarin Red S staining intensity. Additionally, SS-31 reduced NOS2 expression by 50%, highlighting its therapeutic potential in age-related bone loss. SS-31 intervention not only normalizes mitochondrial structure and function, reducing ROS levels and enhancing oxygen consumption rates, but also targets the NOS2 gene, a potential drug target, which upon knockdown, leads to a substantial upregulation of osteogenic markers and an improvement in mitochondrial function. In conclusion, the findings of this study highlight the therapeutic potential of SS-31 in reversing the age-related decline in BM-MSC function by specifically inhibiting NOS2 expression and restoring mitochondrial function. This research provides a scientific basis for the development of new treatments for osteoporosis and other age-related bone diseases, emphasizing the importance of targeting mitochondrial function and cellular senescence in regenerative therapies.

ABSTRACT Podocyte damage is a central feature of lupus nephritis (LN), making the identification of potential therapeutic targets to prevent podocyte injury and improve treatment outcomes essential. ORM1 has been suggested as a significant candidate gene in LN. In this study, mouse podocytes were induced using Immunoglobulin G (IgG) extracted from lupus patients. To investigate the role of ORM1, ORM1 knockdown was performed, and the effects on podocyte viability and apoptosis were assessed using the cell counting kit-8 (CCK-8) assay and flow cytometry. Additionally, autophagy markers LC3II/I and p62 were measured by western blotting and immunofluorescence, and the expression of the AMPK/mTOR signaling pathway was evaluated using western blotting. The results showed an upregulation of ORM1 in the LN model. Upon stimulation with IgG from LN patients, ORM1 knockdown reversed the reduction in podocyte viability, decreased the apoptosis rate, and reduced the elevated levels of autophagy, followed by an increase in AMPK phosphorylation and a decrease in mTOR phosphorylation. In conclusion, these results suggest that ORM1 modulates the expression of autophagy-related components in podocytes through the AMPK/mTOR signaling pathway, thereby influencing podocyte damage in the LN model in vitro.

ABSTRACT Neural stem cell (NSC) possess the essential properties of pluripotency and self-renewal, making them promising candidates for the treatment of neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and spinal cord injuries. While previous studies have identified the long non-coding RNAs (lncRNAs) Pnky as a regulator of NSC differentiation into neurons via RNA splicing, its role in NSC differentiation and proliferation through the Wnt/β-catenin pathway remains unclear. In this study, we investigated the mechanism by which Pnky influences the Wnt/β-catenin pathway to promote NSC differentiation into neurons. Using cck8 assays, western blot analysis, and quantitative polymerase chain reaction (qPCR), we found that Pnky knockdown significantly enhanced NSC proliferation and promoted their differentiation into neurons. Additionally, Pnky knockdown resulted in the downregulation of the neural stem cell marker Nestin and upregulation of the neuronal marker β3-Tubulin, through activation of the β-catenin signaling pathway. Conversely, inhibiting the β-catenin pathway hindered both NSC differentiation and proliferation. These findings suggest that targeting the Pnky-mediated Wnt/β-catenin pathway may offer novel strategies for the treatment, diagnosis, and drug development of central nervous system diseases.

ABSTRACT Objective This study probed the effect of targeted regulation of CD151 by microRNA-214-3p (miR-214-3p) delivered by bone marrow mesenchymal stem cells-secreted exosomes (BMSCs-exo) on oxidative stress and apoptosis of neurons in Alzheimer’s disease (AD). Methods Rat BMSCs were isolated, from which MSCs-exo were extracted and identified. The AD rat model was established and injected with MSC-exo suspension. Meanwhile, miR-214-3p and CD151 interfering lentivirus were transfected in MSCs. After injection, learning and cognitive ability of the rats were assessed, as well as neuronal apoptosis and oxidative stress injury. miR-214-3p and CD151 levels were determined, and their relationship was explored. Results AD rats had prolonged escape latency, weakened learning and cognitive ability, increased neuronal apoptosis in the hippocampal CA3 region, and aggravated oxidative stress. After MSC-exo injection, these changes in AD rats were partially rescued. CD151 was targeted by miR-214-3p, and MSC-exo improved AD in rats through the miR-214-3p/CD151 axis. Conclusion MSC-exo down-regulates CD151 by targeting miR-214-3p to enhance antioxidant capacity, thereby improving the pathological injury of AD rats.