A lymphatic route for a hyperbranched heteroglycan from Radix Astragali to trigger immune responses after oral dosing.

Gut barrier makes a huge research gap between in vivo and in vitro studies of orally bioactive polysaccharides: whether/how they contact the related cells in vivo. A hyperbranched heteroglycan RAP from Radix Astragali, exerting antitumor and immunomodulatory effects in vitro and in vivo, is right an example. Here, we determined first that RAP's antitumor activity is immune-dependent. Being undegraded and non-absorbing, RAP quickly entered Peyer's patches (PPs) in 1 h where it directly targeted follicle dendritic cells and initiated antitumor immune responses. RAP was further delivered to mesenteric lymph node, bone marrow, and tumor. By contrast, the control Dendrobium officinale polysaccharide did not enter PPs. These findings revealed a blood/microbiota-independent and selective lymphatic route for orally administrated RAP to directly contact immune cells and trigger antitumor immune responses. This route bridges the research gap between the in vitro and in vivo studies and might apply to many other bioactive polysaccharides.

Radix Astragalus Polysaccharide Accelerates Angiogenesis by Activating AKT/eNOS to Promote Nerve Regeneration and Functional Recovery.

Peripheral nerve injury (PNI) results in loss of neural control and severe disabilities in patients. Promoting functional nerve recovery by accelerating angiogenesis is a promising neuroprotective treatment strategy. Here, we identified a bioactive Radix Astragalus polysaccharide (RAP) extracted from traditional Chinese medicine (TCM) as a potent enhancer of axonal regeneration and remyelination. Notably, RAP promoted functional recovery and delayed gastrocnemius muscle atrophy in a rat model of sciatic nerve crush injury. Further, RAP treatment may induce angiogenesis in vivo. Moreover, our in vitro results showed that RAP promotes endothelial cell (EC) migration and tube formation. Altogether, our results show that RAP can enhance functional recovery by accelerating angiogenesis, which was probably related to the activation of AKT/eNOS signaling pathway, thereby providing a polysaccharide-based therapeutic strategy for PNI.

Exploration in the Mechanism of Kaempferol for the Treatment of Gastric Cancer Based on Network Pharmacology.

BACKGROUND: Kaempferol is a natural polyphenol in lots of Chinese herbs, which has shown promising treatment for gastric cancer (GC). However, the molecular mechanisms of its action have not been systematically revealed yet. In this work, a network pharmacology approach was used to elucidate the potential mechanisms of kaempferol in the treatment of GC. METHODS: The kaempferol was input into the PharmMapper and SwissTargetPrediction database to get its targets, and the targets of GC were obtained by retrieving the Online Mendelian Inheritance in Man (OMIM) database, MalaCards database, Therapeutic Target Database (TTD), and Coolgen database. The molecular docking was performed to assess the interactions between kaempferol and these targets. Next, the overlap targets of kaempferol and GC were identified for GO and KEGG enrichment analyses. Afterward, a protein-protein interaction (PPI) network was constructed to get the hub targets, and the expression and overall survival analysis of the hub target were investigated. Finally, the overall survival (OS) analysis of hub targets was performed using the Kaplan-Meier Plotter online tool. RESULTS: A total of 990 genes related to GC and 10 overlapping genes were determined through matching the 24 potential targets of kaempferol with disease-associated genes. The result of molecular docking indicated that kaempferol can bind with these hub targets with good binding scores. These targets were further mapped to 140 GO biological process terms and 11 remarkable pathways. In the PPI network analysis, 3 key targets were identified, including ESR1, EGFR, and SRC. The mRNA and protein expression levels of EGFR and SRC were obviously higher in GC tissues. High expression of these targets was related to poor OS in GC patients. CONCLUSIONS: This study provided a novel approach to reveal the therapeutic mechanisms of kaempferol on GC, which will ease the future clinical application of kaempferol in the treatment of GC.

Effect of transcutaneous electrical acupuncture point stimulation on expression of p-JNK in the dorsal root ganglion in a rat model of myofascial pain syndrome.

BACKGROUND: Acupuncture has been used to treat myofascial pain syndrome (MPS) for 2000 years in China, but its mechanisms are still not entirely clear. In the present study, we explored the effects of transcutaneous electrical acupuncture point stimulation (TEAS) at an Ashi acupuncture point on expression of phosphorylated c-Jun N-terminal kinase (p-JNK) in the dorsal root ganglion (DRG) using a rat model of MPS. METHODS: 32 rats were divided into four groups: normal, MPS, MPS+TEAS and MPS+sham- TEAS. MPS was produced by a blunt strike to the left vastus medialis combined with eccentric exercise for 8 weeks. Rats in the MPS+TEAS group received TEAS (6-9 mA, 2 Hz, 30 min) treatment at the Ashi acupuncture point for 2 weeks; rats in the MPS+sham -TEAS group had the same electrodes applied but received no stimulation. Paw withdrawal thermal latency (PWTL) was studied at baseline and on days 3, 7, 11 and 15 after treatment. Haematoxylin and eosin staining was used to examine for morphological changes in the left vastus medialis muscles; expression of p-JNK in the L3-L5 DRG was determined by immunofluorescence staining and western blotting after treatment. RESULTS: Compared with the normal group, PWTL decreased significantly (P<0.01) and the expression of p-JNK in the DRG increased in the MPS and MPS-sham-TEAS groups (P<0.01); compared with the MPS group, PWTL was increased significantly (P<0.01) and expression of p-JNK in the DRG was decreased in the MPS+TEAS group. However, when compared with the normal group, PWTL did not recover to baseline and expression of p-JNK was still higher. CONCLUSION: TEAS treatment may produce an analgesic effect, probably by inhibiting the expression of p-JNK in the DRG of rats with MPS.

Shear bond strengths between alumina-toughened zirconia cores and veneering ceramics and their susceptibility to aging.

OBJECTIVE: To evaluate the shear bond strength (SBS) between alumina-toughened zirconia (ATZ) cores and veneering ceramics, investigate the effect of aging in artificial saliva on SBS and compare it with that of yttria-stabilized tetragonal zirconia polycrystals(Y-TZP). METHODS: Bars of ATZ and Y-TZP were layered with veneering ceramics in accordance to the recommendation of the manufacturer. Half of each group (n = 10) was aged at 134 °C (under 2 bar pressure) in an autoclave for 48 h. Subsequently, all specimens were subjected to shear force in a universal testing machine. The interface and fractured surface of the specimens were evaluated using scanning electron microscopy and X-ray energy dispersive spectroscopy. RESULTS: The initial mean SBS values in MPa±SD were 28.9±8.0 for ATZ and 26.2±7.6 for Y-TZP. After aging, the mean SBS values for ATZ and Y-TZP were 22.9±4.9 MPa and 22.8±6.9 MPa, respectively. Neither the differences between the SBS values of the ATZ and Y-TZP groups nor the influence of aging on all groups were statistically significant. CONCLUSIONS: The SBS between the ATZ core and the veneering ceramics was not affected by aging. The SBS of ATZ to veneering ceramics was not significantly different compared with that of Y-TZP.

Microstructure and mechanical properties of glass-infiltrated Al2O3/ZrO2 nanocomposites.

This work was to investigate the effect of zirconia nanoparticles content on microstructure and mechanical properties of glass-infiltrated alumina/zirconia composites (AZGs). A series of slip-cast zirconia-toughened alumina (ZTA) compacts containing 10, 20, 30 wt% nano-zirconia, respectively, were partially sintered at 1,250°C for 2 h, then infiltrated with lanthanum borosilicate glass of lower thermal expansion at 1,180°C for 4 h. A porosity ranging from 21 to 25% mainly with submicron pore size was demonstrated in the partially-sintered ZTAs. Homogeneous distribution and micro-crystallization of intergranular glass phase was showed in the AZGs. The mechanical strength and fracture toughness of AZGs increased with zirconia content, the maximum (633.5 ± 41.7, 6.7 ± 0.6 MPa m(0.5)) were obtained in 30 wt% zirconia group, which were significantly higher than those in 10 wt% zirconia group (P < 0.05). The improved mechanical performance of AZGs containing 30 wt% zirconia was attributed to their larger zirconia content as well as thinner intergranular glass film.

[Evaluation of alumina effects on the mechanical property and translucency of nano-zirconia all-ceramics].

OBJECTIVE: To study the effects of alumina content on sintered density, mechanical property and translucency of zirconia nanocomposite all-ceramics. METHODS: Specimens of zirconia nanocomposite all-ceramics were divided into five groups based on their alumina content which are 0% (control group), 2.5%, 5.0%, 7.5% and 10.0% respectively. The sintered densities were measured using Archimedes' method. Specimens' bending strengths were measured with three-point bending test (ISO 6872). The visible light transmittances were measured with spectrophotometric arrangements and the fractured surfaces were observed using scanning electron microscope (SEM). RESULTS: The control group of pure zirconia could be sintered to the theoretical density under pressure-less sintering condition. The bending strength was (1100.27 ± 54.82) MPa, the fracture toughness was (4.96 ± 0.35) MPa×m(1/2) and the transmittance could reach 17.03%. The sintered density and transmittance decreased as alumina content increased from 2.5% to 10%. However, the fracture toughness only increased slightly. In all four alumina groups, the additions of alumina had no significant effect on samples' bending strengths (P > 0.05). When the content of alumina was 10%, fracture toughness of specimens reached (6.13 ± 0.44) MPa×m(1/2) while samples' transmittance declined to 6.21%. SEM results showed that alumina particles had no significant effect on the grain size and distribution of tetragonal zirconia polycrystals. CONCLUSIONS: Additions of alumina to yttria-tetragonal zirconia polycrystals could influence its mechanical property and translucency. Additions of the other phase to zirconia ceramics should meet the clinical demands of strength and esthetics.