ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is considered one of the main causes of low back pain and lumbar disc herniation. Various studies have shown that disc cell senescence plays a critical role in this process. however, its role in IDD is yet unclear. In this study, we explored the role of senescence-related genes (SR-DEGs) and its underlying mechanism in IDD. A total of 1325 differentially expressed genes (DEGs) were identified using Gene Expression Omnibus (GEO) database GSE41883. 30 SR-DEGs were identified for further functional enrichment and pathway analysis, and two hub SR-DEGs (ERBB2 and PTGS2) were selected to construct transcription factor (TF)-gene interaction and TF-miRNA coregulatory networks, and 10 candidate drugs were screened for the treatment of IDD. Last but not least, in vitro experiments show that ERBB2 expression decreased and PTGS2 expression increased in human nucleus pulposus (NP) cell senescence model treated with TNF-α. After lentivirus-mediated overexpression of ERBB2, the expression of PTGS2 decreased and the senescence level of NP cells decreased. Overexpression of PTGS2 reversed the anti-senescence effects of ERBB2. The findings in this study suggested that ERBB2 overexpression further reduced NP cell senescence by inhibiting PTGS2 levels, which ultimately alleviated IDD. Taken together, our findings provide new insights into the roles of senescence-related genes in IDD and highlight a novel target of ERBB2-PTGS2 axis for therapeutic strategies.

Preparation of Densified Fine-Grain High-Frequency MnZn Ferrite Using the Cold Sintering Process.

The densified MnZn ferrite ceramics were prepared using the cold sintering process under pressure, with an acetate ethanol solution used as the transient solvent. The effects of the transient solvent, the pressure and annealing temperature on the density, and the micromorphology and magnetic properties of the sintered MnZn ferrites were studied. The densified MnZn ferrite was obtained using the cold sintering process and its relative density reached up to 85.4%. The transient solvent and high pressure are essential to the cold sintering process for MnZn ferrite. The annealing treatment is indispensable in obtaining the sample with the higher density. The relative density was further increased to 97.2% for the sample annealed at 950 °C for 6 h. The increase in the annealing temperature reduces the power loss at high frequencies.

Total flavonoids of Sophora flavescens and kurarinone ameliorated ulcerative colitis by regulating Th17/Treg cell homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is relevant to dysregulation of inflammation and immune processes. Sophora flavescens Aiton is a classic medicine widely used in the treatment of UC in ancient and modern China, alkaloids and flavonoids are the main components. Previous studies reveal that Sophora flavescens Aiton total flavonoids extracts (SFE) exert an anti-UC effect by regulating the intestinal microbe structure and restoring the balance of the "host-microbe" co-metabolic network in UC mice. However, whether SFE influences immune inflammation remains unclear, which is the core link to UC disease. It also remains to be verified flavonoids are the material basis that plays a role in SFE. AIM OF THE STUDY: To identify the action mechanism of the immune-inflammatory regulation of SFE and its main active component Kurarinone against UC. METHODS: This study constructed UC mice and abnormal immune RAW 264.7 cell models, and subsequently used western blotting and flow cytometry (FCM) to evaluate the effects of SFE on the NF-κB pathway and the regulation of immunity in UC mice. Kurarinone was screened from flavonoid compounds of SFE by lipopolysaccharide (LPS)-induced RAW 264.7 cells, and its effect was subsequently investigated in UC mice. Western blotting, ELISA, FCM, and RT-PCR were used to determine the regulation of Kurarinone on the Th17/Treg differentiation and the JAK2/STAT3 signaling pathway. RESULTS: SFE regulated the differentiation of Th17/Treg in peripheral blood and inhibited immune-inflammatory response to treat UC. Various flavonoid components in SFE inhibited the synthesis of IL-6 and TNF-α in RAW 264.7 cells, among which Kurarinone had better effect. This study revealed the therapeutic effects of Kurarinone in UC mice for the first time. Kurarinone promoted the secretion of SIgA to improve the regulation of the intestinal mucosal barrier and resistance to pathogens. It also regulated the transcription level of RORγt and Foxp3 in colon, decreased the expression of pro-inflammatory factor IL-17A and up-regulated the expression of immunosuppressive factors TGF-ß1 and IL-10 in colon. Furthermore, Kurarinone restored intestinal immune system homeostasis by down-regulating the JAK2/STAT3 signaling pathway and regulating the balance of Th17/Treg cell differentiation in UC. CONCLUSIONS: SFE, especially the flavonoid ingredients represented by Kurarinone, has significant effects on immunoregulation against UC. And their mechanism of effect is related to inhibiting the activation of JAK2/STAT3 signaling pathway and regulating differentiation of Th17/Treg cells. KEYWORK: Immunoregulatory; Kurarinone; Th17 cells; Treg cells; Ulcerative colitis.

Effect of the ethyl acetate extract of Sophora flavescens Aiton on diabetic retinopathy based on untargeted retinal metabolomics.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and a leading cause of vision impairment and blindness, which lacks effective diagnostic measures and therapeutic options. Sophora flavescens Aiton or "Kushen" is a traditional Chinese medicine used since ancient times, either alone or in combination, to clear heat, dampness, and tearing, and to treat ocular diseases and improve eyesight. Additionally, the flavonoids of Sophora flavescens Aiton extracted using ethyl acetate (EtOAc) (SFE) is effective in managing diabetes and diabetic vascular complications. In this study, we explored the pharmacodynamic effects and material basis of action of SFE on DR for the first time and elucidated the mechanism based on untargeted retinal metabolomics. Results from the pharmacodynamic studies showed that SFE could reduce blood glucose levels in rats, regulate serum lipopolysaccharide, tauroursodeoxycholic acid, and trimethylamine oxide levels, and significantly improve the structure of retina in rats with DR. Moreover, SFE could protect the blood-retinal barrier, reduce angiogenesis and capillary formation, and inhibit retinal nerve cell apoptosis. A total of 13 compounds were identified in the aqueous humor and retina, which were dihydroflavonoid, isoflavonoid, pterostane flavonoid, chalcone, and dihydroflavonol derivatives. In addition, 39 differential metabolites were screened based on retinal metabolomics data and 23 were found to be affected by SFE, indicating its anti-DR effect by regulating the synthetic metabolic pathways, including lactose, bile acid, glycerophospholipid, arginine, purine, and pyrimidine metabolism pathways. Collectively, our findings elucidated the effects, material basis, and treatment mechanism of SFE on DR systematically and could lay the foundation for promoting the clinical application of Sophora flavescens Aiton.

[Theoretical Verification of Dynamic Lumbar Interspinous Process Stabilization Device with Memory Alloys].

To find an effective method of minimally invasive treatment combining prevention and assistance in the middle zone of conservative treatment and fusion surgery for lumbar degenerative diseases, through the clinical effect observation and the advantage and disadvantage comparison of several commonly used lumbar interspinous dynamic stabilization systems, by analyzing the physiological structure, biomechanics and relevant data of lumbar interspinous processes, based on fully understanding of memory alloy materials, a new dynamic lumbar interspinous fixation device with a memory alloy material has been independently designed and researched, which can not only reconstruct the normal biomechanical characteristics of the lumbar spine and satisfy the normal activities of the human spine, but also avoid damage to the original structure and reduce the incidence of postoperative complications. In addition, the device can be used to optimize the current therapeutic methods. According to our research, the dynamic lumbar interspinous process stabilization device with a memory alloy has theoretically achieved satisfactory results, which can be used to overcome the shortcomings of the existing technology and is superior to the current several dynamic lumbar interspinous process stabilization systems.

Construction of a "Bacteria-Metabolites" Co-Expression Network to Clarify the Anti-Ulcerative Colitis Effect of Flavonoids of Sophora flavescens Aiton by Regulating the "Host-Microbe" Interaction.

Ulcerative colitis (UC) is considered an immune disease, which is related to the dysbiosis of intestinal microbiota and disorders of the host immune system and metabolism. Sophora flavescens Aiton has been used for the clinical treatment of UC in China and East Asia for thousands of years. It has many traditional prescriptions and modern preparations, and its curative effects are definite. We are the first to report that the flavonoids in Sophora flavescens (S. flavescens) Aiton EtOAc extract (SFE) could potentially attenuate the dextran sodium sulfate-induced UC in mice, which changed the current understanding of considering alkaloids as the only anti-UC pharmacological substances of S. flavescens Aiton. Based on the 16S rRNA gene sequencing and metabolomic analysis, it was found that the anti-UC effects of SFE were due to the regulation of gut microbiota, reversing the abnormal metabolisms, and regulation of the short-chain fatty acids synthesis. Notably, according to the interaction networks of specific bacteria and "bacteria and metabolites" co-expression network, the SFE could enrich the abundance of the commensal bacterium Lactobacillus, Roseburia, norank_f__Muribaculaceae, Anaerotruncus, Candidatus_Saccharimona, and Parasutterella, which are proposed as potentially beneficial bacteria, thereby playing vital roles in the treatment of UC.

Land suitability assessment for supporting transport planning based on carrying capacity and construction demand.

With the rapid global urbanization, the unlimited increasing transportation infrastructure has met the needs of urban expansion, but it has caused a series of ecological problems lacking consideration of ecological conservation. The land suitability assessment for supporting transport planning based on carrying capacity and demand for construction is an effective way to promote urban socioeconomic development and ecological conservation. Therefore, we constructed a logical framework of resources and environment supporting, traffic construction demand driving, and ecological protection red line and basic farmland constraining, and applied the analytic hierarchy process (AHP), GIS, three-dimensional magic cube method, and gravity model to evaluate the suitability of expressway development in Sichuan Province, China. The results showed that the spatial difference in the carrying capacity of resources and environment and the demand for expressway construction was relatively high in Sichuan, and those in eastern cities were even higher. The land suitability for supporting transport planning was relatively high, and the suitable areas with a grade from 8 to 10, accounted for 20.77% of the total study area, which could almost meet the demand for transportation infrastructure construction. The land suitability performed a circle structure with Chengdu as the core and gradually decreasing to the periphery. Overall, this study adds new insights to transport planning reform in other similar regions around the world and can provide important references for regional development planning and environmental protection.

A pH-responsive polymer linked with immunomodulatory drugs: synthesis, characteristics and in vitro biocompatibility.

Cancer immunotherapy is a promising method for cancer therapy. Imiquimod (R837) is a molecule that could activate immune systems for cancer immunotherapy, but an easily manufactured biocompatible carrier to deliver R837 may be needed to overcome the disadvantages of R837. Micelles formed by biocompatible copolymers have been widely used to deliver chemotherapeutic drugs but not immunotherapeutic drugs. In this study, R837 was linked to an amphiphilic biodegradable copolymer mPEG-b-PLA via acid-sensitive Schiff bases. The molecular structures were investigated by 1 H nuclear magnetic resonance, gel permeation chromatography and Fourier transform infrared spectroscopy. The product could be self-assembled into micelles with R837 content as high as 22.4%. Owing to acid-cleavable Schiff bases, the release of R837 from micelles was markedly accelerated under acidic media. Consequently, the micelles linked with R837 stimulated the expression of major histocompatibility complex II-stimulating molecules on the surface of RAW 264.7 macrophages at pH 6.5 but not pH 7.4. By using human umbilical vein endothelial cells as the in vitro model, it was shown that the polymer carriers and R837-linked micelles were minimally cytotoxic and did not induce the activation of endothelial cells under physiological pH, which suggested the relatively high biocompatibility. In conclusion, this study successfully developed pH-responsive immunotherapeutic drug-loaded micelles that could activate macrophages at acidic pH in vitro. The high biocompatibility of the micelles to endothelial cells also indicated the potential uses under in vivo conditions.

Clinical Analysis of Internal Fixation Treatment of Intra-articular Calcaneal Fractures with Titanium Plate.

To explore the clinical effect of internal fixation treatment of intra-articular calcaneal fractures with titanium plate, we used open reduction and internal fixation with titanium plate to 48 treated feet from 42 patients with intra-articular calcaneal fractures. The efficacy of surgical treatment was evaluated based on assessment of pain, function, and line of force aspects according to the American Orthopedic Foot and Ankle Society scoring system. Our data show that internal fixation with titanium plate is an effective treatment for calcaneal fractures. It provides satisfactory reduction, reliable fixation, and early rehabilitation.