Saposhnikovia divaricata (Turcz.) Schischk (SD; called "fangfeng" in China) has been widely used in the clinical treatment of rheumatoid arthritis (RA) and has shown well therapeutic effects, but the ...specific mechanisms of action of its bioactive phytochemicals remain unclear.
This study aimed to investigate the molecular biological mechanism of SD in treating RA through a pharmacology-based strategy. The SD-specific core ingredient Prangenidin was screened for further in-depth study.
The bioactive phytochemicals of SD and potential targets for the treatment of RA were screened by network pharmacology, and phytochemicals-related parameters such as pharmacology, and toxicology were evaluated. The protein interaction network was established to screen the core targets, and the correlation between the core targets and RA was further validated by bioinformatics strategy. Finally, molecular docking of core components and corresponding targets was performed. The in vitro experiments were performed to elucidate the regulation of Prangenidin on MH7A cells and on the PI3K/AKT pathway, and the in vivo therapeutic effect of Prangenidin was validated in collagen-induced arthritis (CIA) mice.
A total of 18 bioactive phytochemicals and 66 potential target genes intersecting with the screened RA disease target genes were identified from SD. Finally, core ingredients such as wogonin, beta-sitosterol, 5-O-Methylvisamminol, and prangenidin and core targets such as PTGS2, RELA, and AKT1 were obtained. The underlying mechanism of SD in treating RA might be achieved by regulating pathways such as PI3K/AKT, IL-17 pathway, apoptosis, and multiple biological processes to exert anti-inflammatory and immunomodulatory effects. Molecular docking confirmed that all core ingredients and key targets had great docking activity. Prangenidin inhibited viability, migration, and invasion, and induced apoptosis in MH7A cells. Prangenidin also reduced the production of IL-1β, IL-6, IL-8, MMP-1, and MMP-3. Molecular analysis showed that Prangenidin exerts its regulatory effect on MH7A cells by inhibiting PI3K/AKT pathway. Treatment with Prangenidin ameliorated synovial inflammation in the joints of mice with CIA.
Our findings provide insights into the therapeutic effects of SD on RA, successfully predicting the effective ingredients and potential targets, which could suggest a novel theoretical basis for further exploration of its molecular mechanisms. It also revealed that Prangenidin inhibited viability, migration, invasion, cytokine, and MMPs expression, and induced apoptosis in RA FLSs via the PI3K/AKT pathway.
Numerous antibacterial biomaterials have been developed, but a majority of them suffer from poor biocompatibility. With the purpose of reducing biomaterial-related infection and cytotoxicity, ...friction stir processing (FSP) was employed to embed silver nanoparticles (Ag NPs) in a Ti–6Al–4V (TC4) substrate. Characterization using scanning electron microscopy, transmission electron microscopy, and three-dimensional atom probe tomography illustrates that NPs are distributed more homogeneously on the surface of TC4 as the groove depth increases, and silver-rich NPs with a size from 10 to 20 nm exist as metallic silver diffused into the substrate, where the silver content is 4.3–5.6%. Electrochemical impedance spectroscopy shows that both FSP and the addition of silver have positive effects on corrosion resistance. The modified samples effectively inhibit both Staphylococcus aureus and Escherichia coli strains and slightly reduce their adhesion while not displaying any cytotoxicity to bone mesenchymal stem cells in vitro. The antibacterial effect is independent of Ag-ion release and is likely due to the number of embedded silver NPs on the surface, which directly contact and subsequently destroy the cell membrane. Our study shows that the TC4/Ag metal matrix nanocomposite is a potential infection-related biomaterial and that embedding Ag NPs tightly on a biomaterial surface is an effective strategy for striking a balance between the antibacterial effect and biocompatibility, providing an innovative approach for accurately controlling the cytotoxicity of infection-related biomaterials.
► It focused on the influence of oxygen on microstructures and properties of beta titanium alloys. ► Gum Metal has ‘‘superproperties” different with TNTZ alloy, except for the addition of oxygen. ► ...The change of superelasticity of Ti–Nb–Ta–Zr–O via the addition of oxygen was discussed in the work. ► The comprehensive mechanical properties was improved for Ti–22.5Nb–0.7Ta–2Zr–1.0O alloy.
The influence of oxygen content on microstructure and mechanical properties of Ti–22.5Nb–0.7Ta–2Zr (at.%) alloy was investigated in this work. According to experiments, the grains were refined apparently when the oxygen content was between 1.5% and 2.0%. The ultimate tensile strength (UTS) increased and elongation decreased with increasing oxygen content. But at the content of 1.0%, the elongation was nearly the same to that of the original alloy (about 16%). The elastic modulus remained comparatively low (<65
GPa) when the content was lower than 1.5%, and then increased dramatically. Therefore, there existed the best oxygen content-1.0%, at which fine grains were obtained, as well as UTS of 750
MPa, elongation of 16% and elastic modulus of 65
GPa. The Ti–22.5Nb–0.7Ta–2Zr–1.0O alloy maintained typical ductile fracture characteristics of beta titanium alloy, and had a little superelasticity.
Purpose
The study aimed to examine the outcomes of posterior approach transforaminal lumbar interbody fusion (TLIF) in the treatment of degenerative lumbar scoliosis (DLS) based on the concept of ...intervertebral correction.
Methods
A retrospective analysis was performed on 76 surgical patients (36 males and 40 females) who underwent posterior TLIF and internal fixation based on the concept of intervertebral correction in Shenzhen Traditional Chinese Medicine Hospital from February 2014 to March 2021.The operation duration, intraoperative blood loss, incision length, and complications were recorded. Clinical efficacy was evaluated preoperatively and postoperative time points through the visual analog scale (VAS) and the Oswestry disability index (ODI). The changes in the coronal scoliosis curve (Cobb angle), coronal balance distance (CBD), the sagittal vertical axis (SVA), lumbar lordosis (LL), and pelvic tilt angle (PT) were assessed perioperatively at the last follow-up.
Results
All patients successfully underwent the operation. The average operation duration was 243.81 ± 35.35 (220 − 350) min; the average intraoperative blood loss was 836.27 ± 50.28 (700 − 2500) mL; the average incision length was 8.30 ± 2.33 (8 − 15) cm. The total complication rate was 18.42% (14/76). The VAS score of low back pain, lower extremity pain, and ODI score of patients at the last follow-up was significantly improved compared with those before the operation (
P
< 0.05). At the last follow-up, the Cobb Angle, CBD, SVA, and PT of patients were significantly lower than those before the operation (
P
< 0.05), and LL was higher than those before the operation (
P
< 0.05).
Conclusion
TLIF based on the concept of intervertebral correction for the treatment of DLS may provide favourable clinical outcomes.
•Ti/Zn composites had enhanced mechanical properties.•The biointerface between the fine grain surface and the macrophages was remodeled.•The released Zn ions mediated the bioenergetic remodeling of ...macrophages.•The immunomodulation of Ti/Zn composites promoted the efficiency of osseointegration.
The remodeling of macrophages mediated by biomaterials is an important step in osseointegration. The biointerfacial characteristics shaped by implants and the bioenergetic state derived from macrophages are considered the key to macrophage reprogramming. In this study, the integrated Ti/Zn composites with optimized morphology and bioactive phase were prepared by friction stir processing, which could meet the multi-biofunctional requirements in the application of narrow-diameter implants. The severe plastic deformation and the hindrance of Zn particles to grain growth promote grain refinement, resulting in enhanced mechanical properties. The cell interfacial adhesion mediated by the grain boundary collaborated the energy metabolism reprogramming induced by the released Zn ion, promoting jointly anti-inflammatory cascade in macrophages and favorable osteogenesis in bone marrow mesenchymal stem cells (BMSCs). This study provides a new simultaneous approach of morphology and composition modification for titanium implants, and reveals the important role of grain size and bioactive element in the reversion of macrophage fate as well.
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Intervertebral disk degeneration (IVDD) is closely associated with inflammatory environments. Curcumol has been shown to alleviate inflammation in various disease models, but its effects on IVDD ...remain unclear. In this study, we sought to determine the mechanism of curcumol in tumor necrosis factor (TNF)-α−induced nucleus pulposus cells and a mouse IVDD model.
Nucleus pulposus cells were pretreated with curcumol and then exposed to TNF-α. Cell viability was analyzed using CCK-8, and the messenger ribonucleic acid and protein levels of inflammatory cytokines and PI3K/Akt/NF-κB-related signaling molecules were detected using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. The mouse IVDD model was established by puncturing the C6/7 level of the caudal spine, and then it was treated with curcumol after surgery. Alcian blue/orange G staining was performed to evaluate the severity of intervertebral disk damage, and immunohistochemistry was performed to detect the expression of TNF-α. Toxicologic effects of curcumol were measured by performing hematoxylin-eosin staining and enzyme-linked immunosorbent assay.
Curcumol reduced IL-1β, IL-6, and TNF-α production in NPCs, and the phosphorylation of proteins in the PI3K/Akt/NF-κB signaling pathway was also decreased. The PI3K/Akt/NF-κB-related signaling molecules decreased when TNF-α-induced NPCs were treated with a PI3K inhibitor; however, curcumol did not reverse these effects. In vivo, curcumol ameliorated the progression of IVDD at the early stage and did not exert toxicologic effects.
These results suggest a potential therapeutic use of curcumol to alleviate inflammation via the PI3K/Akt/NF-κB signaling pathway and delay the progression of IVDD.
Implant-associated infections (IAIs) are among the most intractable and costly complications in implant surgery. They can lead to surgery failure, a high economic burden, and a decrease in patient ...quality of life. This manuscript is devoted to introducing current antimicrobial strategies for additively manufactured (AM) titanium (Ti) implants and fostering a better understanding in order to pave the way for potential modern high-throughput technologies. Most bactericidal strategies rely on implant structure design and surface modification. By means of rational structural design, the performance of AM Ti implants can be improved by maintaining a favorable balance between the mechanical, osteogenic, and antibacterial properties. This subject becomes even more important when working with complex geometries; therefore, it is necessary to select appropriate surface modification techniques, including both topological and chemical modification. Antibacterial active metal and antibiotic coatings are among the most commonly used chemical modifications in AM Ti implants. These surface modifications can successfully inhibit bacterial adhesion and biofilm formation, and bacterial apoptosis, leading to improved antibacterial properties. As a result of certain issues such as drug resistance and cytotoxicity, the development of novel and alternative antimicrobial strategies is urgently required. In this regard, the present review paper provides insights into the enhancement of bactericidal properties in AM Ti implants.
Friction stir processing (FSP) was successfully employed to produce gradient multi-phase structured Ti–6Al–4V/Ag nanocomposite surface layer. Microstructural evolution of ...amorphous/nanocrystalline/nano-twin in the surface layer was characterized by TEM in detail. The formation of amorphous phase in the upper surface of stir zone (SZ) was attributed to mechanically driven amorphization caused by dislocation gliding plastic deformation and elements mixing process. The dislocation activities played a dominant role in causing the distortion of lattices and nanocrystallization. The plastic deformation via FSP was responsible for considerable dislocations pile-up and tangle in the potential deformation bands.
Reconstruction of bone defects is still a challenge. In this study, we developed and systematically evaluated a novel injectable strontium-containing hydroxyapatite (Sr-HA) bone cement in which Sr-HA ...powder included 5% Sr and was mixed with a setting liquid that included 5% potassium citrate. This Sr-HA cement was mainly composed of HA and α-tricalcium phosphate (TCP) and exhibited favorable injectability (100%), setting times (the initial setting time was 240 s and the final setting time was 420 s), compressive strength (73.4 MPa), maximal load and maximum bending stress, and excellent radiopacity. In addition, the Sr-HA cement also had excellent biocompatibility that exhibited low cytotoxicity for cell proliferation and no obvious disturbing effect on the osteogenic differentiation of periodontal ligament stem cells (DLSCs) and dental pulp stem cells (DPSCs). However, the Sr-HA cement could slightly promote the osteogenic differentiation of MC3T3 cells, which also implied that it would promote osseointegration between the cement and surrounding bone but would not obviously disturb the biological behavior of DLSCs and DPSCs. An in vivo study further confirmed that Sr-HA cement exhibited favorable osseointegration with the maxilla and tibia. All these findings implied that the novel Sr-HA cement was a suitable bone substitution for bone defects.
•The injectable Sr-HA cement exhibited favorable physical property and biocompatibility.•The injectable Sr-HA cement exhibited favorable osseointegration with bone in vivo.•The injectable Sr-HA cement was a suitable substitution for bone defect.
Ti–
xNb–3Zr–2Ta alloys (
x
=
33, 31, 29, 27, 25) (wt.%) were fabricated by vacuum non-consumable arc melting and hot forging. The hot-forging specimens were solid solution treated at 1053
K for 1.8
...ks followed by water quenching (WQ) and air cooling (AC) respectively. The microstructure of hot-forging specimens with different deformation rate and solid solution treated at different temperatures was investigated. The result showed that a large amount of
α" martensite appeared in the WQ group while only a little amount of
α" phase could be found in the AC group. Moreover, for the WQ group, less niobium resulted in more diffraction peaks of
α" phase in XRD profiles. This result suggested that the stability of β phase decreased with the decrease of Nb content. The microhardness of Ti–
xNb–3Zr–2Ta (wt.%) alloys was improved significantly with the decreasing Nb content in both WQ group and AC group. Increasing deformation ratio could effectively refine β grains for Ti–25N–3Zr–2Ta (wt.%). Both acicular martensite and lath martensite were found in the transmission electron microscope observation of Ti–25Nb–3Zr–2Ta (wt.%) alloy. Martensitic internal twins were identified as well.
► Higher deformation ratio refined grains of as-cast Ti–Nb–Zr–Ta alloys significantly. ► Decreasing Nb content increased microhardness of Ti–Nb–Zr–Ta alloys. ► Rapid cooling was favorable for the formation of α″ martensite. ► Grain coarsening occurred as the solid-solution treatment temperature was elevated.
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