Sustained Release of IGF-1 by 3D Mesoporous Scaffolds Promoting Cardiac Stem Cell Migration and Proliferation

Background/Aims: C-kit-positive cardiac stem cells (CSCs) may have potential as a treatment for cardiovascular disease. However, the low survival rates of c-kit-positive CSCs present a major challenge during the transplantation process. Methods: The hierarchical structure of the 3D cell scaffold was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and N2 adsorption-desorption isotherms. Analyses of the proliferation and migration performances of the IGF-1 scaffold on c-kit-positive CSCs were conducted by experiments including QuantiT PicoGreen dsDNA and transwell assays. Results: In this study, we synthesized for the first time a novel hierarchical macro-mesoporous silica material (denoted MS15-c) in a one-pot procedure for the release of insulin-like growth factor-1 (IGF-1) and a three-dimensional (3D) cell scaffold. Both macropores and mesopores were visible in MS15-c and enabled the sustained release of IGF-1, extending its half-life and enhancing CSC proliferation and migration. Proliferation and migration were detected by QuantiT PicoGreen dsDNA and transwell assays, respectively. Moreover, an in vivo experiment was conducted to detect heart function with the addition of MS15-c. The new strategy proposed in this paper may extend the bio-applications of 3D cell scaffolds, thus permitting the sustained release of growth factors and efficient promotion of cell proliferation. Conclusion: This work successfully demonstrated an effective strategy for the construction of MS15-c cell scaffolds with hierarchical macro-mesoporous structures. The macro-mesoporous structures gave cell scaffolds the ability to release a growth factor to facilitate cell growth, while the scaffold structure promoted cell proliferation

Value of Intracardiac Echocardiography in the Interventional Closure of Patent Foramen Ovale with Adjacent Atrial Septal Defect

Objective. This study aimed to investigate the application value of intracardiac echocardiography (ICE) in transcatheter closure of a patent foramen ovale (PFO) combined with an adjacent atrial septal defect (ASD). Methods. This retrospective study included five patients with PFO combined with adjacent ASD who underwent transcatheter closure and were admitted to the Zhongshan Hospital of Fudan University from June to September 2023. General conditions, ultrasound and ICE findings, and operative data were recorded and followed up for 2–6 months. Results. Of the five patients, two and three had embolic stroke of undetermined source and migraine, respectively, aged 45.6 ± 12.0 years. All patients underwent successful transcatheter closure via the PFO tunnel under the guidance of ICE, without complications or new stroke, and showed significantly reduced migraine at the follow-up. Conclusion. In patients with PFO combined with adjacent ASD, closure of a PFO tunnel could be successfully achieved under ICE guidance; its clinical efficacy was accurate and worthy of promotion

Tanshinone IIA Alleviates Pirarubicin-Induced Cytotoxicity in H9c2 Cardiomyocytes via Regulation of Hippo Signaling Pathway

Malignant tumor is considered as one of the fatal diseases worldwide with high incidence and mortality. Pirarubicin (THP) is an anti-cancer drug commonly used in the treatment of patients with malignancies. In view of that THP exists the cardiotoxic effects, its clinical application is restricted. Tanshinone IIA (TSA) is a core active monomer drawn from Salvia miltiorrhiza that possesses the cardioprotective properties. In the present study, we proposed to unveil the potential and latent mechanism of TSA in the cardiotoxicity caused by THP. Our results validated that THP treatment gave rise to the injury of cardiomyocytes. Moreover, administration of TSA abrogated the impacts of THP on H9c2 cells. A myriad of literatures demonstrate that Hippo pathway plays a critical role in the development of multiple cardiovascular disorders. Hence, we further explored the relationship between TSA and Hippo pathway. It was proven that THP contributed to the activation of Hippo pathway and TSA treatment inhibited Hippo pathway. More importantly, we revealed that TSA attenuated THP-mediated cytotoxicity in cardiomyocytes through modulating Hippo pathway, which provide insights into the improvement of THP-induced toxic and side effects.</jats:p

MALAT1: A Pivotal lncRNA in the Phenotypic Switch of Gastric Smooth Muscle Cells via the Targeting of the miR-449a/DLL1 Axis in Diabetic Gastroparesis

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). Our previous study suggested that the expression of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is closely related to DGP. However, the role of MALAT1 in DGP pathogenesis remains unclear. Here, we aim to characterize the role of MALAT1 in DGP. First, we analyzed the lncRNA expression profiles through lncRNA sequencing. Next, we detected MALAT1 expression in the stomach tissues of DGP model mice and diabetic patients. Then, we investigated the role and mechanisms of MALAT1 in the proliferation, migration, phenotypic switch, and carbachol-induced intracellular C

MALAT1: A Pivotal lncRNA in the Phenotypic Switch of Gastric Smooth Muscle Cells via the Targeting of the miR-449a/DLL1 Axis in Diabetic Gastroparesis

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). Our previous study suggested that the expression of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is closely related to DGP. However, the role of MALAT1 in DGP pathogenesis remains unclear. Here, we aim to characterize the role of MALAT1 in DGP. First, we analyzed the lncRNA expression profiles through lncRNA sequencing. Next, we detected MALAT1 expression in the stomach tissues of DGP model mice and diabetic patients. Then, we investigated the role and mechanisms of MALAT1 in the proliferation, migration, phenotypic switch, and carbachol-induced intracellular Ca2+ changes in human gastric smooth muscle cells (HGSMCs) under high glucose (HG) conditions, using short hairpin RNA technology, RNA immunoprecipitation, and dual-luciferase reporter assays. We show that MALAT1 expression was upregulated in the gastric tissues of DGP model mice, the adjacent healthy tissues collected from diabetic gastric cancer patients with DGP symptoms, and in HGSMCs cultured under HG conditions. Functionally, MALAT1 knockdown in vitro impacted the viability, proliferation, migration and promoted the phenotypic switch of HGSMCs under HG conditions. Additionally, we show that MALAT1 sponged miR-449a, regulating Delta-like ligand 1 (DLL1) expression in HGSMCs; any disturbance of the MALAT1/miR-449a/DLL1 pathway affects the proliferation, migration, phenotypic switch, and carbachol-induced Ca2+ transient signals in HGSMCs under HG conditions. Collectively, our data highlight a novel regulatory signaling pathway, the MALAT1/miR-449a/DLL1 axis, in the context of DGP.</jats:p