Garnerpenn1032
Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of extracellular matrix (ECM) protein in the lungs. Transforming growth factor (TGF) β-induced ECM protein synthesis contributes to the development of IPF. Tranilast, an anti-allergy drug, suppresses TGFβ expression and inhibits interstitial renal fibrosis in animal models. However, the beneficial effects of tranilast or its mechanism as a therapy for pulmonary fibrosis have not been clarified.
We investigated the in vitro effect of tranilast on ECM production and TGFβ/SMAD2 pathway in TGFβ2-stimulated A549 human alveolar epithelial cells, using quantitative polymerase chain reaction, Western blotting, and immunofluorescence. In vitro observations were validated in the lungs of a murine pulmonary fibrosis model, which we developed by intravenous injection of bleomycin.
Treatment with tranilast suppressed the expression of ECM proteins, such as fibronectin and type IV collagen, and attenuated SMAD2 phosphorylation in TGFβ2-stimulated A549 cells. In addition, based on a wound healing assay in these cells, tranilast significantly inhibited cell motility, with foci formation that comprised of ECM proteins. Histological analyses revealed that the administration of tranilast significantly attenuated lung fibrosis in mice. Furthermore, tranilast treatment significantly reduced levels of TGFβ, collagen, fibronectin, and phosphorylated SMAD2 in pulmonary fibrotic tissues in mice.
These findings suggest that tranilast inhibits pulmonary fibrosis by suppressing TGFβ/SMAD2-mediated ECM protein production, presenting tranilast as a promising and novel anti-fibrotic agent for the treatment of IPF.
These findings suggest that tranilast inhibits pulmonary fibrosis by suppressing TGFβ/SMAD2-mediated ECM protein production, presenting tranilast as a promising and novel anti-fibrotic agent for the treatment of IPF.
Steroids are known to inhibit osteogenic differentiation and subsequent bone formation in bone mesenchymal stem cells (BMSCs). However, little is known about the role of BMSC exosomes (Exos) and tRNA-derived small RNAs (tsRNAs) in steroid-induced osteonecrosis of the femoral head (SONFH). The objective of this study was to characterize the tsRNA expression profiles of plasma Exos collected from SONFH patients and healthy individuals using small RNA sequencing and further explore the effect of BMSC Exos carrying specific tsRNAs on osteogenic differentiation.
Based on insights from small RNA sequencing, five differentially expressed (DE) tsRNAs were selected for quantitative real-time polymerase chain reaction (qRT-PCR). The regulatory networks associated with interactions of the tsRNAs-mRNA-pathways were reconstructed. The osteogenesis and adipogenesis in BMSCs were detected via ALP and oil red O staining methods, respectively.
A total of 345 DE small RNAs were screened, including 223 DE tsRNAs. The DE ts enhanced osteogenic differentiation ability of dexamethasone-induced BMSCs. Our results provide novel insights into the osteogenic effect of BMSC Exos carrying specific tsRNAs on SONFH.[This corrects the article DOI 10.2147/DDDT.S237699.].
Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive system. Studies have shown that pseudolaric acid B (PAB) has several pharmacological effects like anti-microtubule, anti-angiogenesis, and antitumor functions, while the effect and mechanism of PAB on esophageal cancer are still unclear. This study was designed to investigate the effects of PAB on ESCC.
To study the effects of PAB on the biological function through a series of in vitro and in vivo experiments.
The results revealed that PAB inhibited the proliferation, invasion, and migration, but promoted the apoptosis of ESCC. Bay 11-7085 IKK inhibitor Moreover, PAB restrained the growth of cancer cells in vivo and inhibited the angiogenesis of HUVEC in mice with ESCC. CD147 expression was increased in the esophageal squamous cell lines, and interference with CD147 hindered the proliferation, invasion, and migration of ESCC cells, and inhibited the growth and angiogenesis of the esophageal squamous cell line. PAB reduced the expression of CD147 in vivo and in vitro. The expression of MMP2, 3, and 9 was increased after overexpression of CD147, which provided the opportunity to reverse the role of PAB in inhibiting proliferation, invasion, migration, and angiogenesis of ESCC.
The results revealed that PAB inhibited the proliferation, invasion, migration, and angiogenesis of ESCC in vitro and in vivo by CD147. PAB is a promising monomer for therapy of ESCC, providing references for future research on ESCC treatment.
The results revealed that PAB inhibited the proliferation, invasion, migration, and angiogenesis of ESCC in vitro and in vivo by CD147. PAB is a promising monomer for therapy of ESCC, providing references for future research on ESCC treatment.
The production of nano-erythrosomes (NEs) by extrusion, which is considered the "gold standard", has several disadvantages such as difficult equipment assembly, long procedure time, variable pressure, and problems with sterility. An alternative approach, using ultrasound probe, has been shown to overheat the sample and have suboptimal results compared to the extrusion method. In our study, we propose, develop, and test a new method for the fabrication of NEs based on shear force and then compare it to the "gold standard" extrusion approach.
The new method consists of mechanical shear force disruption of the hemoglobin-depleted erythrocyte ghost membranes, with the aid of a rotor stator based tissue homogenizer. Using the same batches of erythrocyte ghost membranes, we compared NEs produced by shear force to NEs produced by the well-established extrusion approach. NEs were characterized for yield, size, encapsulation efficiency, morphology, and stability by flow cytometry (FC), transmission electron microsindicates a future potential development of large-scale NEs production and industrial application, which has been a challenge for the extrusion method.
The newly proposed shear force method allows faster, easier, and highly reproducible NEs production when compared to the conventional extrusion approach. The new setup allows simultaneous production of sterile batches of NEs, which have homogenous size distribution, good stability, and improved shelf life storage. The ability of the shear force method to process also high concentration samples indicates a future potential development of large-scale NEs production and industrial application, which has been a challenge for the extrusion method.
