Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Mechanisms of Stigmasterol in the Treatment of Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints associated with systemic comorbidities. Sinomenium acutum is regarded as an effective traditional Chinese medicine (TCM) for the treatment of RA. Materials and Methods: Based on network pharmacology and Gene Expression Omnibus (GEO) database, 33 RA-related differentially-expressed genes (DEGs) targeting active compounds of Sinomenium acutum were initially screened in our investigation. Results: Gene Ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) analyses found the important involvement of these DEGs in osteoclast differentiation, and finally 5 core DEGs, including NCF4, NFKB1, CYBA, IL-1ß and NCF1 were determined through protein-protein interaction (PPI) network. We also identified the related active component of Sinomenium acutum include Stigmasterol. Finally, in order to experimentally verify these results, a rat model of collagen-induced arthritis (CIA) was established, and subsequently treated with Stigmasterol solution. Conclusion: Similar to the healing effect of Indomethacin, Stigmasterol was observed to reduce the levels of inflammatory factors (IL-6 and IL-1ß) and osteoclast differentiation-related factors (RANKL, ACP5 and Cathepsin K), which can also reduce the arthritis index score and alleviate the degree of pathological injury of rat ankle joints. The predictions and experimental data uncover the involvement of Stigmasterol, an active component of Sinomenium acutum, in regulation of osteoclast differentiation, exerting great medicinal potential in the treatment of RA.

Norfloxacin-induced effect on enhanced biological phosphorus removal from wastewater after long-term exposure.

In this study, long-term experiments were performed under synthetic wastewater conditions to evaluated the potential impacts of norfloxacin (NOR) (10, 100 and 500 µg/L) on enhanced biological phosphorus removal (EBPR). Experimental result showed that long-term exposure to 10 µg/L NOR induced negligible effects on phosphorus removal. The presence of 100 µg/L NOR slightly decreased phosphorus removal efficiency to 94.41 ± 1.59 %. However, when NOR level further increased to 500 µg/L, phosphorus removal efficiency was significantly decreased from 97.96 ± 0.8 5% (control) to 82.33 ± 3.07 %. The mechanism study revealed that the presence of 500 µg/L NOR inhibited anaerobic phosphorus release and acetate uptake as well as aerobic phosphorus uptake during long-term exposure. It was also found that 500 µg/L NOR exposure suppressed the activity of key enzymes related to phosphorus removal but promoted the transformations of intracellular polyhydroxyalkanoate and glycogen. Microbial analysis revealed that that the presence of 500 µg/L NOR reduced the abundances of polyphosphate accumulating organisms but increased glycogen accumulating organisms, as compared the control.

Unique electrocardiographic pattern "w" wave in lead I of idiopathic ventricular arrhythmias arising from the distal great cardiac vein.

BACKGROUND: The ECG characteristics of the distal coronary venous system ventricular arrhythmias (VAs) share common features with VAs arising from the aortic cusps or the endocardial left ventricular outflow tract (LVOT) beneath the cusps. The purpose of this study was to identify specific electrocardiographic and electrophysiological characteristics of VAs originating from the distal great cardiac vein (GCV). METHODS: Based on the successful ablation site, patients with idiopathic VAs from the distal GCV, left coronary cusp (LCC) or the subvalvular left ventricular outflow tract (LVOT) area were included in the present study. RESULTS: The final population consisted of 39 patients (35 males, mean age 51 ± 23 years). All VAs displayed a right bundle branch block (RBBB) morphology with inferior axis. Among these patients, 15 were successfully ablated at the GCV, 15 at the LCC and 9 at the subvalvular region. A "w" pattern in lead I was present in 12 out of 15 (80%) VAs originating from the distal GCV compared to none of VAs arising from the other two sites (p < 0.01). VAs with a GCV origin exhibited more commonly increased intrinsicoid deflection time, higher maximum deflection index and wider QRS duration compared to LCC and subvalvular sites (p < 0.05). Acceptable pace mapping at the successful ablation site was achieved in 10 patients. After an average of 36 ± 24 months follow up, 14 (93.3%) patients were free from VAs recurrence. CONCLUSION: A "w" pattern in lead I may distinguish distal GCV VAs from VAs arising from the LCC or the subvalvular region.

Effective treatment of oily scum via catalytic wet persulfate oxidation process activated by Fe2.

Oily scum, a hazardous by-product of petroleum industry, need to be deposed urgently to reduce environmental risks. This paper introduces catalytic wet persulfate oxidation (CWPO) process in the treatment of oily scum to realize risk relief. Under the activation of heat and Fe2+, persulfate (PS) was decomposed into sulfate radicals and hydroxyl radicals, which played a major role on the degradation of petroleum hydrocarbons. The effects of wet air oxidation (WAO) and CWPO process on the degradation of oily scum were compared. In CWPO process, the total petroleum hydrocarbons (TPHs) content of oily scum was decreased from 92.63% to 16.75%, which was still up to 70.19% in WAO process. The degradation rate of TPHs in CWPO process was about 3.38 times higher than that in WAO process. The great performance of CWPO process was also confirmed by elemental analysis, which indicated that the C and H contents of oily scum were reduced significantly by CWPO process. These results indicated that CWPO process has high potential on the degradation of oily scum for environmental protection.

Ginkgo biloba extract EGb761 attenuates brain death-induced renal injury by inhibiting pro-inflammatory cytokines and the SAPK and JAK-STAT signalings.

This study aimed to investigate the protective effects of EGb761, a Ginkgo Biloba extract, against brain death-induced kidney injury. Sixty male Sprague Dawley rats were randomly divided into six groups: sham, brain-death (BD), BD + EGb b48h (48 hours before BD), BD + EGb 2 h (2 hours after BD), BD + EGb 1 h, and BD + EGb 0.5 h. Six hours after BD, serum sample and kidney tissues were collected for analyses. The levels of blood urea nitrogen (BUN) and serum creatinine significantly elevated in the BD group than in sham group. In all the EGb761-treated BD animals except for the BD + Gb 2 h group, the levels of BUN and serum creatinine significantly reduced (all P < 0.01). EGb761 attenuated tubular injury and lowered the histological score. In addition, the longer duration of drug treatment was, the better protective efficacy could be observed. EGb761 significantly reduced IL-1ß, IL-6, TNF-α, MCP-1, IP-10 mRNA expression and macrophage infiltration in the kidney. EGb761 treatment at 48 hour before brain death significantly attenuate the levels of p-JNK-MAPK, p-p38-MAPK, and p-STAT3 proteins (all P < 0.05, compared to BD group). In summary, our data showed that EGb761 treatment protected donor kidney from BD-induced damages by blocking SAPK and JAK-STAT signalings. Early administration of EGb761 can provide better protective efficacy.

Taishan Pinus massoniana pollen polysaccharides promote immune responses of recombinant Bordetella avium ompA in BALB/c mice.

To study the effects of Taishan Pinus massoniana pollen polysaccharides (TPPPS) on Bordetella avium outer membrane protein A (ompA) recombinant protein vaccine, ompA was expressed, confirmed by Western blotting and mixed with TPPPS. Female BALB/c mice were randomly divided into six groups (I-VI). Groups I, II, and III were treated with TPPPS-ompA at doses of 200, 400, and 800 mg/ml, respectively. Groups IV, V, and VI were treated with Freund's adjuvant-ompA, pure ompA, and physiological saline, respectively. On days 3, 7, 14, 21, 28, 35, 42, and 49 after the first vaccination, antibody titers, interleukin-2 (IL-2) levels, peripheral blood CD4+ and CD8+ levels, and T lymphocyte proliferation rates in peripheral blood, as well as secreting-type immunoglobulin A (SIgA) levels in the duodenum, were measured. The antibody titers against ompA, IL-2, T lymphocyte proliferation rate, CD4+, and CD8+ in Group II were significantly (P<0.05) higher than those in other groups. However, little difference in SIgA content was observed among Groups I, II, and IV. These results indicated that TPPPS strengthened humoral and cellular immune response against recombinant ompA vaccine and 400 mg/ml TPPPS showed significance (P<0.05) compared with Freund's adjuvant. Therefore, TPPPS can be developed into an adjuvant for recombinant protein vaccines or plant-derived medicine for animal husbandry.

Aconitine blocks HERG and Kv1.5 potassium channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum has been widely used to treat various diseases in China for a long time. However, improper use of this drug results in severe intoxication. Aconitine (ACO), a diterpenoid alkaloid from aconitum, mainly contributes to cardio-toxic effects of aconitum and has also been commonly known to induce arrhythmias in animal models. However, its pro-arrhythmic mechanisms are not clear. AIM OF THE STUDY: The effects of ACO on HERG and Kv1.5 channels were investigated. MATERIALS AND METHODS: HERG and Kv1.5 channels were expressed in Xenopus laevis oocytes, and the resulting currents were recorded using a two-microelectrode voltage clamp technique. RESULTS: In HERG channels, ACO exhibited a blockade in a voltage- and time-dependent manner. The blockade was enhanced by further activation of currents, which were consistent with an open-channel blockade. In Kv1.5 channels, ACO produced a voltage-, time-, and frequency-dependent inhibition. The blockade was enhanced by higher rates of stimulation, consistent with preferential binding of the drug to the open state. In addition, ACO blocked Kv1.5 and HERG channels in a concentration-dependent manner with an IC(50) of 0.796+/-0.123 and 1.801+/-0.332 microM, respectively. CONCLUSIONS: ACO blocks HERG and Kv1.5 potassium channels in the open state. Blockade of potassium channels, particular the HERG channel, may be one of the important mechanisms of how ACO induces arrhythmias.

[The effects of 40 mg atorvastatin on serum lipids, inflammatory markers and clinical events in ACS patients post PCI].

OBJECTIVE: To assess the safety and effects of 40 mg atorvastatin on serum lipids, inflammatory markers and clinical events in ACS patients post PCI. METHODS: A total of 92 patients with ACS post successful PCI were randomly divided into atorvastatin 10 mg/d (group A) and atorvastatin 40 mg/d (group B) on top of the standard medical therapy. Blood were taken at baseline, 4, 12 and 24 weeks for serum alanine aminotransferase (ALT), lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloprotease-9 (MMP-9) measurements. The major adverse cardiac events (MACE) were also observed. RESULTS: There was no significant difference in medication withdrawn (2 vs. 3 cases) due to increased ALT (3 times higher than normal) and incidence of MACE (5 vs. 7 cases) between the groups. TC and LDL were significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 24 weeks post medication (P < 0.05) while TG and HDL remained unchanged. hs-CRP was significantly reduced at 12 and 24 weeks in both groups compared to baseline and the reduction was more significant in group B than that in group A at 24 weeks. MMP-9 was significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 12 weeks post medication (P < 0.05). CONCLUSION: Both atorvastatin doses significantly reduced TC, LDL, hs-CRP and MMP-9 in ACS patients post PCI and the reduction was more significant in high dose atorvastatin group at 24 weeks while the MACE and drug withdraw rates were similar between the groups.