[Application of microneedle-assisted percutaneous drug delivery system in treatment of rheumatoid arthritis:a review].

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.

[Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope].

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

[Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

[Mechanism of Linderae Radix against gastric cancer based on network pharmacology and in vitro experimental validation].

The present study explored the main active ingredients and the underlying mechanism of Linderae Radix the treatment of gastric cancer by network pharmacology, molecular docking, and in vitro cell experiments. TCMSP, OMIM and GeneCards database were used to obtain the active ingredients of Linderae Radix to predict the related targets of both Linderae Radix and gastric cancer. After screening the common potential action targets, the STRING database was used to construct the PPI network for protein interaction of the two common targets. Enrichment analysis of GO and KEGG by DAVID database. Based on STRING and DAVID platform data, Cytoscape software was used to construct an "active ingredient-target" network and an "active ingredient-target-pathway" network. Molecular docking was performed using the AutoDock Vina to predict the binding of the active components to the key action targets, and finally the key targets and pathways were verified in vitro. According to the prediction results, there were 9 active components, 179 related targets of Radix Linderae, 107 common targets of Linderae Radix and gastric cancer, 693 biological processes, 57 cell compositions, and 129 molecular functions involved in the targets, and 161 signaling pathways involved in tumor antigen p53, hypoxia-indu-cible factor 1, etc. Molecular docking results showed that the core component, jimadone, had high binding activity with TP53. Finally, in an in vitro experiment, the screened radix linderae active ingredient gemmadone is used for preliminarily verifying the core targets and pathways of the human gastric cancer cell SGC-7901, The results showed that germacrone could significantly inhibit the proliferation of gastric cancer cells and induce the apoptosis of SGC-7901 by regulating the expression of p53, Bax, Bcl-2 and other key proteins. In summary, Radix Linderae can control the occurrence and development of gastric cancer through multi-components, multi-targets and multi-pathways, which will provide theoretical basis for further clinical discussion on the mechanism of Radix Linderae in treating gastric cancer.

Extracellular matrix-coating pedicle screws conduct and induce osteogenesis.

BACKGROUND: The purpose of the present study was to study the effects of the extracellular matrix-coating pedicle screws on the conduction and induction of bone formation in young sheep. METHODS: Pedicle screws [coated with collagen/chondroitin sulfate (coll/CS), hydroxyapatite (HA), and coll/CS/HA or uncoated] were randomly implanted into the L2-L5 pedicles of sheep. In the first stage, a static experiment was performed. In the second stage, a loading test was performed by implanting connecting rods. After 3 months, the lumbar vertebrae with the screws were removed and examined by micro-CT, histological, and biomechanical analyses. RESULTS: Under non-loading conditions, there is bone formation around the surfaces of coated screws. Bone formation on the surface of the coll/CS/HA coating of pedicle screws was the highest. In terms of the trabecular bone morphology parameters of the region of interest around the surface of the pedicle screws, those associated with coll/CS/HA coatings were highest under non-loading conditions, the pullout strength of the coll-/CS-/HA-coated screws was the highest and that of the uncoated screws was minimal. Under loading conditions, the maximum pullout strength of each group of pedicle screws was less than that of the pedicle screws in the non-loading state. CONCLUSIONS: Under non-loading conditions, the organic and inorganic components of the titanium pedicle screw coatings can conduct or induce bone formation around the surface of the screws. The ability of the coll/CS/HA coating to induce bone formation was the strongest. Under loading conditions, a large amount of connective tissue formed around the surface of the screws in each group.

Computation and molecular pharmacology to trace the anti-rheumatoid activity of Angelicae Pubescentis Radix.

BACKGROUND: The mechanism of action of Angelicae Pubescentis Radix in rheumatoid arthritis treatment is complex; the pathways and protein targets involved remain unclear. This study predicted the targets and signaling pathways of Angelicae Pubescentis Radix for rheumatoid arthritis treatment using network pharmacology and molecular docking technology and clarified its mechanism of action using in vitro cellular experiments. METHODS: Angelicae Pubescentis Radix active components and related targets were retrieved from the traditional Chinese medicine systems pharmacology database. All human proteins were mined from the global protein database, and the network of active components and targets of Angelicae Pubescentis Radix was drawn using Cytoscape 3.7.1. GeneCard, Online Mendelian Inheritance in Man, and DrugBank databases were used to mine rheumatoid arthritis-related genes. Metascape was used for Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes enrichment pathways. ß-sitosterol's molecular docking was determined using AutoDock Tools; pathway verification was performed in the Kyoto Encyclopedia of Genes and Genomes database, and the verified genes were input into the Human Protein Atlas database to observe the expression levels in various human body tissues. RESULTS: Eight main active components were screened out of Angelicae Pubescentis Radix from the traditional Chinese medicine systems pharmacology database, and 60 targets related to major active ingredients were obtained. Forty-two core pathogenic rheumatoid arthritis-related genes were screened from GeneCard and other related databases. The enrichment of the Kyoto Encyclopedia of Genes and Genomes pathway included the vascular endothelial growth factor signaling pathway that proved to be the decisive pathway for rheumatoid arthritis treatment by a high degree value. In vitro experiments confirmed that Angelicae Pubescentis Radix mainly regulated cell proliferation and survival through the vascular endothelial growth factor signaling pathway and showed significant therapeutic effects on rheumatoid arthritis. The prostaglandin endoperoxide synthase 2 gene was associated with rheumatoid arthritis via pathway verification and monitoring of human gene expression levels. CONCLUSIONS: The mechanism of the multi-component, multi-target, and multi-channel treatment of rheumatoid arthritis via Angelicae Pubescentis Radix was explored using network pharmacology and molecular docking technology, providing new thinking and research directions for future rheumatoid arthritis treatment using Angelicae Pubescentis Radix.

Age-related differences in the biological parameters of vertebral cancellous bone from Chinese women.

BACKGROUND: With aging, the human fracture risks gradually increase. This is mainly due to the corresponding changes of the biomechanical parameters of human bone presents with aging. We measured the microstructural parameters of lumbar bone from women in several age groups by micro-computed tomography and scanning electron microscopy. We observed changes in lumbar cancellous bone mineral density and in biomechanical parameters with aging to elucidate the relationship between age and risk of fracture. We provide theoretical support for human pathology, fracture risk increased with age and the individualized of each age group. METHODS: Thirty-two fresh L3 vertebral bodies were donated from 32 women, aged 20-59 years and were divided into four age groups: 20 to 29 years (group A); 30 to 39 years (group B); 40 to 49 years (group C); and 50 to 59 years (group D). Conventional lumbar separation was performed by removing soft tissue and subsidiary structures, leaving only the vertebral body. The vertebral body was cut into halves along the median sagittal plane, maintaining the upper and lower end-plates of each half, and used for biomechanical, morphological, and density measurements. RESULTS: Comparing group A to B, the rod-like trabecular thickness (Tb.Th) decreased; the trabecular spacing (Tb.Sp) increased; the plate-like Tb.Th decreased; bone mineral density, tissue mineral density, bone volume fraction, and bone surface fraction decreased, and the elastic modulus and the ultimate stress decreased (all changes P < 0.05). Similar significant (P < 0.05) trends were obtained when comparing group C to D. With aging, the collagen cross-linking capacity declined, the thickness of the collagen fibrils was variable (ranging from almost the same to loose, sparse, or disordered), and the finer collagen fibrils between the thick filaments were disorganized. CONCLUSIONS: In women aged 20 to 59 years, the rod-like and plate-like Tb.Th of the vertebral body decreased, while Tb.Sp increased. Additionally, the density, elastic modulus, and ultimate stress of the cancellous bone decreased with age. These associated changes in bone microstructure, density, and biomechanics with age may lead to an increasing risk of osteoporosis and fracture.

Palladium nanoparticle/chitosan-grafted graphene nanocomposites for construction of a glucose biosensor.

Graphene (GR) was covalently functionalized with chitosan (CS) to improve its biocompatibility and hydrophilicity for the preparation of biosensors. The CS-grafted GR (CS-GR) rendered water-soluble nanocomposites that were readily decorated with palladium nanoparticles (PdNPs) using in situ reduction. Results with TEM, SEM, FTIR, Raman and XRD revealed that CS was successfully grafted without destroying the structure of GR, and PdNPs were densely decorated on CS-GR sheets with no aggregation occurring. A novel glucose biosensor was then developed through covalently immobilizing glucose oxidase (GOD) on a glassy carbon electrode modified with the PdNPs/CS-GR nanocomposite film. Due to synergistic effect of PdNPs and GR, the PdNPs/CS-GR nanocomposite film exhibited excellent electrocatalytical activity toward H(2)O(2) and facilitated high loading of enzymes. The biosensor demonstrated high sensitivity of 31.2 µA mM(-1)cm(-2) for glucose with a wide linear range from 1.0 µM to 1.0mM as well as a low detection limit of 0.2 µM (S/N=3). The low Michaelis-Menten constant (1.2mM) suggested enhanced enzyme affinity to glucose. These results indicated that PdNPs/CS-GR nanocomposites held great potential for construction of a variety of electrochemical biosensors.