To detect the expression and distribution of hypoxia-inducible factor-1alpha (HIF-1alpha) in nasal polyps, to explore the relationship of HIF-1alpha with vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS), and to investigate the role of HIF-1alpha in the pathogenetic mechanism of nasal polyps.Using the techniques of immunohistochemistry and reverse transcription polymerase chain reaction, the expressions of HIF-1alpha, VEGF, iNOS protein and HIF-1alpha mRNA were examined. The specimens were obtained from patients underwent SMR surgery during the same period, including thirty-one nasal polyps and ten inferior turbinate tissues.According to immunohistochemical research, the expressions of HIF-1alpha, VEGF and iNOS were higher in nasal polyps than those in inferior turbinate tissue (P < 0.01); The result of RT-PCR showed that there was no significant difference between the expression of HIF-1alpha mRNA in nasal polyps and inferior turbinate tissues (P > 0.05); No correlation was found between the expression of HIF-1alpha and the clinical stages of nasal polyps (F = 0.42, P > 0.05); There was a positive correlation between the expression of HIF-1alpha and that of VEGF (r = 0.630, P < 0.05). No significant correlation was found between the expression of HIF-1alpha and that of Inos (r = 0.144, P > 0.05).Although the mRNA level of HIF-1alpha did not change much, the expression of its protein was significantly higher in nasal polyps than in inferior turbinate tissues. There was no correlation between the expression of HIF-1alpha and the clinical stages. A positive correlation was found between HIF-1alpha and VEGF, but no correlation was detected between the HIF-1alpha and iNOS. In conclusion, our study indicates that hypoxia may play an important role in the pathogenetic mechanism of nasal polyps.
Single-element focused transducers applied in blood-brain barrier (BBB) disruption experiments to optimize intravascular therapies in CNS diseases have the advantage of low cost and portability. Most of the in vivo studies on non-human primates report the use of single-element transducers with an annular spherical shape and a central frequency of 500 kHz. High-frequency ultrasound has smaller focal area and less standing-wave effect but lower transcranial penetration efficiency. Our study reports the feasibility and safety concerns of BBB opening by single-element spherical transducers with central frequencies of 300, 650 and 800 kHz on two rhesus macaques.Pulsed ultrasound exposure (3-minute duration, 0.5-1% duty cycle) combined with microbubble injection (SonoVue, 0.2uL/g) was used to disrupt the BBB of the monkeys under the magnetic resonance imaging (MRI) guidance. Gadolinium contrast-enhanced MRI was used to confirm and evaluate the BBB opening after sonication. T2-weighted fast spin echo and T2 * -weighted gradient echo sequences were used to check the post-sonication complications, such as edema and micro-bleeding.Contrast enhancement was found on the post-sonication T1 weighted images for all experiments, showing that the BBB was successfully opened under all the three frequencies on both monkeys. The enhanced area was largest at the lowest frequency. No obvious hypo-intensity or hyper-intensity was observed on either the T2 * weighted gradient echo images or T2-weighted fast-spin echo images, implying the safety of the opening procedure. However, signal enhancement was also observed in the subarachnoid space of the sulci for all frequencies, indicating that the BBB was also disrupted in the propagation path outside the focal area.The feasibility of BBB opening with single-element transducer under frequencies ranging from 300 kHz to 800 kHz was confirmed by experiments in two non-human primates in vivo. Further investigation into the off-target effects and transducer configurations is needed for safety optimization.
To evaluate the feasibility of in vivo magnetic resonance imaging (MRI) with 1.5T system tracking of the survival, migration and differentiation of magnetically labeled seed cells-bone marrow-derived mesenchymal stem cells (MSCs) injected into the articular cavity.Rabbit MSCs were isolated, purified, expanded, and then coincubated in vitro with supermagnetic iron oxide particles (SPIO) and 5-bromo-2-deoxyuridine (BrdU). Prussian blue staining and transmission electron microscopy were performed to observe the intracellular iron. Some labeled MSCs were subjected to chondrogenic differentiation and the phenotype was examined to assess their chondrogenic differentiation capacity. MSCs colabeled with SPIO nanoparticles and (BrdU were suspended in chitosan and glycerophosphate (C-GP) gel. Eighteen rabbits underwent damage to the femoral trochlea to create cartilage defect models, and randomly divided into 3 groups 1 week later: Group A (n=6) undergoing injection of the MSC suspension in C-GP gel into the intra-articular space of knee joints, Group B (n=6), injected with un-labeled MSC suspension in C-GP gel, and Group C (n=6), without injection. MRI of the knee was performed 1, 4, 8, and 12 weeks after the injection respectively on a certain numbers of rabbits. and then the rabbits were killed with their knee joints taken out to undergo immunohistochemistry. The MR imaging findings were compared with the histological findings.Prussian blue staining and transmission electron microscopy showed intracytoplasmic nanoparticles in the SPIO-labeled cells. Safranin-O staining showed deposition of proteoglycan and type II collagen outside both the labeled and unlabeled MSCs, showing chondrogenesis. GRE T2-weighted MR image showed marked hypointense signal void areas, representing the implanted MSCs, in the intra-articular space after the MSC injection in Group A that persisted for 12 weeks at least; 2 week after the MSC injection hypointense signal could be seen in the defect, which peaked in the signal intensity about 4 weeks later, and then gradually decreased in the signal intensity; and 12 weeks after the injection no recognizable hypointense signal in the defect was detected. Immunohistochemical staining demonstrated the presence of Prussian blue-positive cells and BrdU-positive cells in the tissue sections in the areas corresponding well to the signal intensity loss regions in the MRI images. Group B and Group C showed no signal intensity loss in the intra-articular spaces by GRE T2-weighted MR imaging. Histological observation showed that the defects were repaired with fibrocartilage in Groups A and B, and with fiber tissue in Group C.Labeled with SPIO, the MSCs remains their ability of chondrogenic differentiation. It is feasible to track the fate and dynamic redistribution of magnetically labeled MSCs, the seed cells, injected into the articular cavity by 1.5T MRI, an efficient noninvasive technique.
Background: Osteoporosis (OP) is an age-related bone disease that has emerged as a worldwide public health concern due to its increasing incidence and high disability rate. Tanshinol [D (+) β-3,4-dihydroxyphenyl lactic acid, TS], a water-soluble component extracted from Salvia miltiorrhiza, has proven to be effective in attenuating OP in vitro and in vivo . However, there is insufficient evidence to support its clinical application. Objective: This meta-analysis aimed to investigate available OP animal model studies to demonstrate the antiosteoporosis effects of TS in a systematic manner. Methods: Electronic searches of related studies were conducted in the following databases: EMBASE, PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese VIP Database, Chinese Biomedical Literature Database, and Wanfang. The retrieval date was January 2022, and there were no time or language restrictions. The CAMARADES 10-item quality checklist was utilized to test the risk of potential bias for each study, and modifications were performed accordingly. The primary outcome was bone mineral density (BMD, which included the femur and lumbar spine); and secondary outcomes were parameters for trabecular bone such as bone volume over total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), conditions of the femur (including bone maximum load and bone elastic load), and markers of bone metabolism (serum osteocalcin, S-OCN). Results: A total of nine studies including 176 rats were chosen for this analysis. Egger’s test revealed the presence of publication bias in various studies regarding the primary outcome. According to this systematic review, TS significantly increased the BMD of the femur (BMD-femur) ( SMD = 4.40; 95% CI = 1.61 to 7.19; p = 0.002, I 2 = 94.6%), BMD of the lumbar spine (BMD-lumbar) (SMD = 6.390; 95% CI = 2.036 to 10.744; p = 0.004, I 2 = 95.9%), BV/TV (SMD = 0.790; 95% CI = 0.376 to 1.204; p = 0.000, I 2 = 10.8), Tb.N (SMD = 0.690; 95% CI = 0.309 to 1.071; p = 0.000, I 2 = 12%), Tb.Th (SMD = 0.772; 95% CI = 0.410 to 1.134; p = 0.000, I 2 = 32.2%), and S-OCN (SMD = 3.13; 95% CI = 0.617 to 5.65; p = 0.015, I 2 = 92.3%), while the Tb.Sp level was markedly decreased in OP models in comparison to the controls (SMD = −0.822; 95% CI = −1.207 to −0.437; p = 0.000, I 2 = 0%). Moreover, TS treatment was associated with a significant improvement of the bone biomechanical indicators, including bone maximum load (SMD = 0.912; 95% CI = 0.370 to 1.455; p = 0.001, I 2 = 40%) and elasticity load (SM D = 0.821; 95% CI = 0.290 to 1.351; p = 0.002, I 2 = 0%). Conclusion: Collectively, our findings suggest that TS can improve BMD, bone microarchitecture, bone biomechanics, and S-OCN expression in rats, implying that it could be used clinically in the future. Systematic Review Registration: https://inplasy.com/inplasy-2022-3-0053/ , identifier [INPLASY202230053].
AbstractBackground:Rheumatoid arthritis is a common inflammatory disease, with osteonecrosis of the femoral head being one of its common complications. However, the treatment of "osteonecrosis of the femoral head " is limited with insufficient drug development. The aim of this study is to explore molecular pathways and core genes associated with rheumatoid arthritis-induced osteonecrosis of the femoral head and investigate pharmacological targeting therapy for rheumatoid arthritis-induced osteonecrosis of the femoral head.Methods:In this analysis, intersection genes involved with both " rheumatoid arthritis " and "osteonecrosis of the femoral head " were identified using the Gene-Cards database, followed by functional analysis. The software programs STRING Online and Cytoscape were used to build protein-protein interaction (PPI) networks. Upon completion of the drug-gene interaction study, core genes and potential medicines were identified.Results:The Gene-Cards database discovered a total of 110 genes overlapped by "rheumatoid arthritis " and "osteonecrosis of the femoral head ". Following functional analysis, 108 important genes were selected. Subsequently, PPI analysis revealed 29 genes that may be targeted by 12 medicines and were candidates to treat rheumatoid arthritis-induced osteonecrosis of the femoral head.Conclusions:We used the Gene-Cards database and pathway analysis to identify highly related genes between " rheumatoid arthritis " and "osteonecrosis of the femoral head " and to explore potential therapeutic drugs. The following genes were investigated: HGF, MMP9, IL-1, EP300, SERPINC1, PLG, F5, and APOA1 are all involved in rheumatoid arthritis-induced osteonecrosis of the femoral head. It was found that fondaparinux, garcinol, canakinumab, and andecaliximab could be used as promising medications to treat rheumatoid arthritis-induced osteonecrosis of the femoral head.
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