[Retracted] Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells.

[This retracts the article DOI: 10.3892/ol.2016.5474.].

Inhibitory Effect of Salicin on Staphylococcus aureus Coagulase.

The massive use of antibiotics has resulted in an alarming increase in antibiotic resistance in Staphylococcus aureus (S. aureus). This study aimed to identify the inhibitory effect of salicin on S. aureus. Coagulase (Coa) activity was assessed using in vitro Coa assays and Western blot, thermal shift assay (TSA), fluorescence quenching and molecular docking experiments were conducted to verify the interaction between salicin and Coa. An in vivo mouse pneumonia model demonstrated that salicin can reduce the virulence of S. aureus. In vitro Coa assays elucidated that salicin directly inhibited Coa activity. The Western blot and TSA results suggested that salicin did not block the expression of Coa but affected the thermal stability of the protein by binding to Coa. The fluorescence quenching, molecular docking and molecular dynamics assays have found that the most promising binding site between salicin and Coa was GLN-97. The pneumonia model of mice infected with S. aureus revealed that salicin could not only reduce the content of lung bacteria in mice but also prolong their survival. Salicin was identified as a novel anti-infective candidate compound with the potential to target Coa and inhibit its activity by binding to it, which would facilitate the development of roadmaps for future research.

Isovanillic acid protects mice against Staphylococcus aureus by targeting vWbp and Coa.

Aim: Our primary objective was to investigate the protective effects and mechanisms of isovanillic acid in mice infected with Staphylococcus aureus Newman. Methods: In vitro coagulation assays were used to validate vWbp and Coa as inhibitory targets of isovanillic acid. The binding mechanism of isovanillic acid to vWbp and Coa was investigated using molecular docking and point mutagenesis. Importantly, a lethal pneumonia mouse model was used to assess the effect of isovanillic acid on survival and pathological injury in mice. Results & Conclusion: Isovanillic acid reduced the virulence of S. aureus by directly binding to inhibit the clotting activity of vWbp and Coa, thereby reducing lung histopathological damage and improving the survival rate in mice with pneumonia.

7,8-Dihydroxyflavone attenuates the virulence of Staphylococcus aureus by inhibiting alpha-hemolysin.

Staphylococcus aureus (S. aureus), a Gram-positive bacteria, is an incurable cause of hospital and community-acquired infections. Inhibition bacterial virulence is a viable strategy against S. aureus infections based on the multiple virulence factors secreted by S. aureus. Alpha-hemolysin (Hla) plays a crucial role in bacteria virulence without affecting bacterial viability. Here, we identified that 7,8-Dihydroxyflavone (7,8-DHF), a natural compound, was able to decrease the expression of and did not affect the in vitro growth of S. aureus USA300 at a concentration of 32 µg/mL. It was verified by western blot and RT-qPCR that the natural compound could inhibit the transcription and translation of Hla. Further mechanism studies revealed that 7,8-DHF has a negative effect on transcriptional regulator agrA and RNAIII, preventing the upregulation of virulence gene. Cytotoxicity assays showed that 7,8-DHF did not produce significant cytotoxicity to A549 cells. Animal experiments showed that the combination of 7,8-DHF and vancomycin had a more significant therapeutic effect on S. aureus infection, reflecting the synergistic effect of 7,8-DHF with antibiotics. In conclusion, 7,8-DHF was able to target Hla to protect host cells from hemolysis while limiting the development of bacterial resistance.

Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells.

The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays. Arctigenin exposure also induced a 60-75% reduction in colony formation compared with vehicle-treated control cells. However, arctigenin was not observed to affect the invasiveness of glioma cells. Arctigenin significantly increased the proportion of cells in the G0/G1 phase and reduced the number of cells in the S phase, as compared with the control group (P<0.05). Western blot analysis demonstrated that arctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin-dependent kinase 4 proteins. Additionally, arctigenin was able to induce apoptosis in glioma cells, coupled with increased expression levels of cleaved caspase-3 and the pro-apoptotic BCL2-associated X protein. Furthermore, arctigenin-induced apoptosis was significantly suppressed by the pretreatment of cells with Z-DEVD-FMK, a caspase-3 inhibitor. In conclusion, the results suggest that arctigenin is able to inhibit cell proliferation and may induce apoptosis and cell cycle arrest at the G0/G1 phase in glioma cells. These results warrant further investigation of the anticancer effects of arctigenin in animal models of gliomas.

Relationship between adiponectin receptor 1 gene polymorphisms and ischemic stroke.

OBJECTIVE: Previous study suggested adiponectin receptor 2 (ADIPOR2) genetic polymorphisms were associated with the risk of ischemic stroke. However, the relation between adiponectin receptor 1 (ADIPOR1) gene polymorphism and stroke remains unclear. METHODS: In the present study, we utilized the polymerase chain reaction-sequencing method to detect rs2275737 and s1342387 genotypes of ADIPOR1 gene in 300 cases of ischemic stroke patients and 300 age- and sex- matched healthy controls. RESULTS: For rs2275737, we found A allele carriers have increased risk to ischemic stroke (OR=2.570, 95% CI: 1.999-3.305); also, we found rs1342387 A allele was associated with the risk for stroke (OR=1.351, 95% CI: 1.074-1.699). After adjusted for confounders such as hypertension, diabetes, and smoking, we found the association remains significant. CONCLUSION: ADIPOR1 genetic polymorphism may increase the risk of ischemic stroke.

Low-Molecular-Weight Fucoidan Inhibits the Viability and Invasiveness and Triggers Apoptosis in IL-1ß-Treated Human Rheumatoid Arthritis Fibroblast Synoviocytes.

Fucoidan is a sulfated polysaccharide found mainly in various species of brown algae and brown seaweed. Here, we investigated the effects of low-molecular-weight (LMW) fucoidan (4 kDa) on interleukin-1beta (IL-1ß)-stimulated rheumatoid arthritis fibroblast-like synoviocyte (RAFLS). 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and annexin V/propidium iodide assay were used to assess cell viability and apoptosis, respectively. Transwell assay was performed to evaluate cell invasion. Reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay analysis was done to measure gene expression and secretion. Nuclear factor-kappa B (NF-κB) DNA binding activity was determined by electrophoretic mobility shift assay. LMW fucoidan dose-dependently inhibited the viability and induced apoptosis of IL-1ß-treated RAFLS. Fucoidan attenuated IL-1ß-induced invasion of RAFLS and decreased the expression and secretion of metalloproteinase (MMP)-1, MMP-3, and MMP-9. Fucoidan suppressed NF-κB binding activity, p65 nuclear translocation, and IκB-α degradation in IL-1ß-stimulated RAFLS. Additionally, IL-1ß-induced phosphorylation of p38 but not ERK or JNK was significantly impaired by fucoidan treatment. LMW fucoidan reduces the viability, survival, and invasiveness of IL-1ß-treated RAFLS, which is associated with inhibition of NF-κB and p38 activation. LMW fucoidan may have therapeutic potential in the treatment of rheumatoid arthritis.

[Clinical efficacy on vertebrobasilar insufficiency treated with auricular acupuncture].

OBJECTIVE: To compare the efficacy on vertebrobasilar insufficiency (VBI) between auricular acupuncture therapy and oral administration of medicine. METHODS: Sixty patients of VBI were randomized into an auricular acupuncture therapy group and a medicine group, 30 cases in each one. In the auricular acupuncture group, acupuncture was applied bilaterally to gan (CO12) and jiejie (HX8) on the ears and needles were retained for 15 min. After needle withdrawal, the vaccariae semen were fixed with plaster at naogan (AT3, 4i), zhen (AT3), jing (AH12), shen (CO10) and pi (CO13) on the ears. In the medicine group, flunarizine hydrochloride capsules (Sibelium), 5mg were prescribed for oral administration, once every night. The treatment lasted continuously for 2 weeks (14 days) in the two groups. In 2 weeks, the clinical efficacy was assessed and the transcranial doppler (TCD) examination was performed. RESULTS: After treatment, the symptom scores were all apparently reduced in the patients of the two groups (P < 0.01, P < 0.05). Compared with the medicine group, the reduced score was much more obvious in the auricular acupuncture group (P < 0.05), indicating the significant difference. After treatment, with TCD examination, the blood velocity was increased to different degrees in the patients of low velocity type in the auricular acupuncture group and the medicine group; that was reduced to different degrees in the patients of high velocity type in the auricular acupuncture group and the medicine group. All of them were different significantly as compared with those before treatment (all P < 0.05). But the difference was not significant between the two groups (both P > 0.05). In comparison of clinical efficacy between the two groups, the effective rate was 93.3% (28/30) in the acupuncture group and better than 76.7% (23/30) in the medicine group, indicating the significant difference in comparison (P < 0.05). CONCLUSION: The auricular acupuncture therapy achieves the definite efficacy on VBI and the efficacy is better than flunarizine hydrochloride capsules.