Triptolide exposure induces oxidative stress and decreases oocyte quality in mouse.

Triptolide is a major active ingredient isolated from the traditional Chinese medicine Tripterygium wilfordii, which has anti-inflammatory, anti-cancer, and immunomodulatory effects. However, in clinical studies, triptolide has toxic side effects on the heart, kidney, liver and reproductive organs. With respect to female reproductive toxicity, damaging effects of triptolide on the ovary have been reported, but it has remained unknown whether oocytes are affected by triptolide. Therefore, this study established a concentration gradient of triptolide exposure in mice using 0 (control), 30, 60, and 90 µg triptolide/kg body weight/day administered by gavage. Triptolide administration for 28 d reduced body weight and ovarian weight and affected the developmental potential of oocytes. The triptolide-treated group exhibited meiotic failure of oocytes due to impaired spindle assembly, chromosome alignment, and tubulin stability. Triptolide was also found to induce mitochondrial dysfunction, autophagy and early apoptosis, iron homeostasis, and abnormal histone modifications. These adverse effects could be associated with oxidative stress induced by triptolide. In conclusion, our findings suggest detrimental effects of triptolide on mouse oocytes and, thus, on female reproduction.

A Systematic Review and Network Meta-Analysis about the Efficacy and Safety of Tripterygium wilfordii Hook F in Rheumatoid Arthritis.

Objective: This study aims to evaluate the efficacy of various conventional synthetic DMARDs, including Tripterygium wilfordii Hook F (TwHF) for treating rheumatoid arthritis (RA) by network meta-analysis. Methods: We retrieved the related literature from online databases and supplemented it by using a manual retrieval method. Data was extracted from the literature and analyzed with STATA software. Results: A total of 21 trials (5,039 participants) were identified. Assessment of ACR20 response found that TwHF combined with methotrexate (MTX) had the greatest probability for being the best treatment option among the treatments involved, while TwHF used singly was second only to TwHF combined with MTX. Assessment of ACR50 response found that TwHF combined with MTX ranked second in all treatment options after cyclosporine A (CsA) combined with leflunomide (LEF) and TwHF alone, followed by TwHF combined with MTX. Assessment of ACR70 response found that CsA combined with LEF ranked first, TwHF combined with LEF ranked second, TwHF combined with MTX ranked third, and TwHF used singly ranked fourth. In the safety analysis, TwHF had the least probability of adverse event occurrence, followed by TwHF combined with MTX, which ranked first and second, respectively. Conclusion: Compared with the current csDMARDs for treating RA, the efficacy of TwHF was clear, and TwHF combined with MTX performed well under various endpoints. In the future, large, rigorous, and high-quality RCTs are still needed to confirm the benefits of TwHF therapy on RA.

GHRH expression plasmid improves osteoporosis and skin damage in aged mice.

The hormone secretion of GHRH-GH-IGF-1 axis in animals was decreased as aging. These hormones play an important role in maintaining bone mass and bone structure, and also affect the normal structure and function of the skin. We used plasmid-based technology to deliver growth hormone releasing hormone (GHRH) to elderly mice. In the current study, 80 and 120 µg/kg pVAX-GHRH plasmid expression plasmid were injected into old mice, the serum GHRH and insulin-like growth factor-1(IGF-1) content were increased within three weeks (P < 0.05). In the groups of 80 and 120 µg/kg plasmid, the content of procollagen type I N-terminal pro-peptide (PINP) in the serum was increased(P < 0.05), and the content of C-terminal telopeptides of type I collagen (CTX-1) in the serum was reduced significantly (P < 0.05). Furthermore, the expression of osteoprotegerin (OPG) and osteocalcin (OCN) in the femur also was increased(P < 0.05). The bone mineral density(BMD)、trabecular bone volume (BV/TV) and trabecular number(Tb.N) of mouse femur were increased significantly (P < 0.05) and trabecular separation(Tb.Sp) was decreased(P < 0.05). There were more trabecular bones in the bone marrow cavity and the trabecular bones are thicker in the groups of 80 and 120 µg/kg plasmid relative to control. The superoxide dismutase (SOD) content in the skin was increased(P < 0.05), and the malondialdehyde (MDA) content was reduced significantly (P < 0.05). Meanwhile, the skin moisture content also increased significantly(P < 0.05). Moreover, the expression of matrix metalloproteinase 3(MMP3) and matrix metalloproteinase 9(MMP9) was decreased in the skin(P < 0.05). The thickness of the dermis and epidermis of the skin had increased significantly(P < 0.05). Skin structure is more dense and complete in the two groups. These results indicate that 80 and 120 µg/kg plasmid-mediated GHRH supplementation can improve osteoporosis and skin aging in aged mice.

[Effects of temperature and phosphorus application on wheat growth at seedling stage and phosphorus form in calcareous fluvo-aquic soil]. / 温度和施磷对石灰性潮土小麦苗期生长及磷形态的影响.

The effects of temperature and phosphate fertilizer application on wheat seedling growth and soil inorganic phosphorus transformation in calcareous fluvo-aquic soil were examined in a pot experiment. The results showed that temperature and phosphorus were important factors affecting wheat growth but without significant interaction. The effect of temperature on wheat growth was greater than that of phosphate fertilizer, and 15 ℃ was the suitable temperature for wheat seedling. Compared with the treatment without P application (-P) at 5 ℃, phosphate fertilizer treatment (+P) promoted the growth of wheat seedling. Shoot and root biomass increased by 18.2% and 33.3%, the accumulation of phosphorus in shoot and root were increased by 30.6% and 13.3%, and the root-shoot ratio, plant height, tillering number and root activity were increased by 3.5%, 10.0%, 10.5% and 70.3%, respectively. At 15 ℃, the effect of phosphorus fertilizer application did not affect wheat biomass and tiller, increased P accumulation in shoot and root of wheat by 32.3% and 23.8%, and increased the ratio of root to shoot, plant height and root activity by 15.6%, 2.5% and 32.8% respectively. There were no significant promoting effects on wheat growth between different phosphate applications at 25 ℃. At three temperatures, phosphate application significantly increased the contents of Olsen-P, Ca2-P, Ca8-P, Al-P and Fe-P. When treated with -P and +P, temperature had no significant effect on Ca2-P content, but had significant effect on the Olsen-P, Ca8-P, Al-P, Fe-P contents. The contents of Ca8-P and Fe-P were 5 ℃＞15 ℃＞25 ℃; Al-P content was 25 ℃＞15 ℃＞5 ℃. Wheat could absorb and utilize Ca2-P, Ca8-P, Al-P, Fe-P at seedling stage. The availability of Al-P, Fe-P to wheat was significantly lower than that of Ca2-P, Ca8-P. There was no significant difference of soil pH, O-P and Ca10-P across all treatments. In conclusion, temperature mainly affected the absorption of phosphorus by affecting wheat growth, and the application of phosphorus fertilizer at low temperature could significantly promote the growth of wheat. High temperature could accelerate the fixation of available phosphorus in calcareous soil, a process could be alleviated by phosphorus application.

[Effect of Tripterygium Glycosides Tablets in treating rheumatoid arthritis:a systematic review and Meta-analysis].

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.

[Identification of biomarkers to response of Tripterygium Glycosides Tablets acting on rheumatoid arthritis by integrating transcriptional data mining and biomolecular network analysis].

Growing clinical evidence shows that a partial rheumatoid arthritis( RA) patient treated with Tripterygium Glycosides Tablets( TGT) may fail to achieve clinical improvement. It is of great clinical significance to predict the therapeutic effect of TGT in RA. Therefore,the aim of the current study was to identify potential biomarkers for TGT treatment in RA. Affymetrix EG1.0 arrays were applied to detect gene expression in peripheral blood mononuclear cells obtained from 6 RA patients( 3 responders and 3 non-responders) treated with TGT. By integrating differential expression data analysis and biomolecular network analysis,360 mRNAs( 185 up-regulated and 175 down-regulated) and 24 miRNAs( 7 up-regulated and 17 down-regulated) which were differentially expressed between TGT responder and non-responder groups were identified. A total of 206 candidate target genes for the differentially expressed miRNAs were obtained based on miRanada and Target Scan databases,and then the miRNA target gene coexpression network and miRNA-mediated gene signal transduction network were constructed. Following the network analyses,three candidate miRNAs biomarkers( hsa-miR-4720-5 p,hsa-miR-374 b-5 p,hsa-miR-185-3 p) were identified as candidate biomarkers predicting individual response to TGT. Partialleast-squares( PLS) was applied to construct a model for predicting response to TGT based on the expression levels of the candidate gene biomarkers in RA patients. The five-fold cross-validation showed that the prediction accuracy( ACC) of this PLS-based model efficacy was 100.00%,100.00%,100.00%,66.67% and 66.67% respectively,and all the area under the receiver operating characteristic curve( AUC) were 1.00,indicating the highly predictive efficiency of this PLS-based model. In conclusion,the integrating transcription data mining and biomolecular network investigation show that hsa-mir-4720-5 p,hsa-mir-374 b-5 p and hsa-mir-185-3 p may be candidate biomarkers predicting individual response to TGT. In addition,the PLS model based on the expression levels of these candidate biomarkers may be helpful for the clinical screen of RA patients,which potentially benefit individualized therapy of RA in a daily clinical setting.

Tripterygium wilfordii Hook F versus conventional synthetic disease-modifying anti-rheumatic drugs as monotherapy for rheumatoid arthritis: a systematic review and network meta-analysis.

BACKGROUND: Tripterygium wilfordii Hook F (TwHF), a medicinal plant that has been widely used in Chinese traditional medicine, is proven effective for treating rheumatoid arthritis (RA), but its clinical efficacy and safety remain largely undefined in comparison with conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). METHODS: PubMed, Embase, Cochrane Library, CNKI, VIP, CBM, and WanFang Databases. Endpoints were ACR 20, 50, and 70, and the number of withdrawals due to adverse events. Initially, traditional pairwise meta-analysis was performed by using a random-effects model. Then, we performed network meta-analysis to compare different therapies by using frequentist approach. RESULTS: A total of 22 trials (5255 participants) were identified. By direct comparison, TwHF was superior to sulphasalazine according to ACR 20, 50 and 70. TwHF was superior to placebo according to ACR 20 and 50. By indirect comparisons, TwHF was superior to methotrexate, leflunomide, sulphasalazine, tacrolimus, minocycline and placebo according to ACR 20. Ranking by the Surface under the Cumulative Ranking curve (SUCRA) values showed that TwHF had the greatest probability for being the best treatment option according to ACR 20 (92.0 %) and ACR 50 (81.3 %), and the highest probability to be in the second (57.8 %) ranking position after leflunomide (69.6 %) according to ACR 70. By both direct and indirect comparisons, TwHF caused no more significant withdrawals than the placebo. The SUCRA values showed that TwHF had the highest probability to rank sixth (26.7 %) after the placebo (45.6 %) in causing withdrawals. CONCLUSIONS: Our data suggest that TwHF is effective and safe in the treatment of RA and has better clinical efficacy in terms of ACR 20 and 50 than existing conventional synthetic DMARDs. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.

[Clinical trials of treatment of acute facial paralysis with pain by blood-letting plus acupuncture in patients].

OBJECTIVE: To observe the clinical therapeutic effect of blood-letting plus acupuncture intervention for acute facial paralysis with pain (damp-heat type of liver and gallbladder). METHODS: A total of 120 cases of acute facial paralysis with pain were randomly and equally divided into control group and treatment group. Patients of the control group were treated by simple acupuncture therapy only, and patients of the treatment group treated by acupuncture plus bloodletting at the ipsilateral Yangbai(GB 14) and Quanliao (SI 18), and Dazhui (GV 14) and Yifeng (TE 17), alternatively. Shallow-acupuncture stimulation of ipsilateral Cuanzhu (BL 2), Sizhukong (TE 23), Sibai (ST 2), Dicang (ST 4), Jiache (ST 6), Yingxiang (SP 9), and bilateral Hegu (LI 4), Yanglingquan (GB 34) and Xingjian (LR 2) was administered for 30 min, once daily for one month. The patients' facial pain degree was evaluated by visual analogue scale (VAS), and the pain duration during acute stage was recorded. The facial nerve function and facial nerve function recovery (grade II) time were determined by using Sunnybrook Facial Grading scale and House-Brackmann (HB) grading scale, respectively. RESULTS: In comparison with pre-treatment, the post-aurem pain scores after the first treatment and after the acute stage were significantly decreased, and the facial nerve function scores after the treatment were significantly increased in both control and treatment groups (P < 0.01), and the effects of the treatment group were significantly superior to those of the control group (P < 0.01). The post-aurem pain duration and the time of facial nerve function recovery (HB) of the treatment group were considerably lower than those of the control group (P < 0.01). Of the 58 and 59 facial palsy patients in the control and treatment groups, 16 (27.6%) and 24 (40.7%) were cured, 18 (31.0%) and 23 (39.0%) experienced marked improvement, 15 (25.9%) and 10 (16.9%) were improved, and 9 (15.5%) and 2 (3.4%) were failed, with the effective rate being 85.0% and 96.6%, respectively. CONCLUSION: Bloodletting combined acupuncture is effective in the treatment of acute facial paralysis with pain.

Sorption of ammonium and phosphate from aqueous solution by biochar derived from phytoremediation plants.

The study on biochar derived from plant biomass for environmental applications is attracting more and more attention. Twelve sets of biochar were obtained by treating four phytoremediation plants, Salix rosthornii Seemen, Thalia dealbata, Vetiveria zizanioides, and Phragmites sp., sequentially through pyrolysis at 500 °C in a N2 environment, and under different temperatures (500, 600, and 700 °C) in a CO2 environment. The cation exchange capacity and specific surface area of biochar varied with both plant species and pyrolysis temperature. The magnesium (Mg) content of biochar derived from T. dealbata (TC) was obviously higher than that of the other plant biochars. This biochar also had the highest sorption capacity for phosphate and ammonium. In terms of biomass yields, adsorption capacity, and energy cost, T. dealbata biochar produced at 600 °C (TC600) is the most promising sorbent for removing contaminants (N and P) from aqueous solution. Therefore, T. dealbata appears to be the best candidate for phytoremediation application as its biomass can make a good biochar for environmental cleaning.

[Clinical effect analysis of ankylosing spondylitis treated by Chinese medical syndrome differentiation].

OBJECTIVE: To evaluate the curative effect and safety of Bushen Qiangji Decoction (BQD) and Qingre Qiangji Decoction (QQD) in treating ankylosing spondylitis (AS) patients, and to verify the clinical utility of AS syndrome differentiation and treatment scheme [Shen-deficiency induced stasis obstruction syndrome (SDISOS) and dampness-heat obstruction syndrome (DHOS) being two basic syndrome types, Shen invigorating blood activating method (SIBAM) and heat clearing dampness resolving method (HCDRM) being two basic treatment methods]. METHODS: Totally 354 AS patients of SDISOS and DHOS were randomly assigned to the treatment group and the control group using a multi-center randomized, positive drug parallel-controlled clinical trail. Patients in treatment group were treated by BQD or QQD according to syndrome typing, while those in the control group took Sulfasalazine enteric-coated tablet (SECT), 24 weeks as one therapeutic course. After treatment, the clinical efficacy was evaluated by using ASAS20 standard (set by Asessment in Ankylosing Spondylitis working group), Chinese medical efficacy evaluation standards, and BASDAI, BASFI, BASMI, night-pain index, spinal pain index, PGA, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: After 24 weeks of treatment by BQD or QQD, ASAS20 standard rate was 86.75% in the treatment group, and the total effective rate of Chinese medical syndrome was 85.47%. They could significantly reduce patients' integrals of Chinese medical syndrome, BASDAI, BASFI, BASMI, night-pain index, spinal pain index, and PGA (all P < 0.01). CONCLUSIONS: QQD and BQD got confirmable clinical effects in treating AS, providing strong evidence of evidence-based medicine for syndrome differentiation and treatment of AS.

Dragon's blood may have radioprotective effects in radiation-induced rat brain injury.

Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis. It is a traditional medicinal that is used for wound healing and to stop bleeding. Its main biological activity appears to be from phenolic compounds found in Dragon's blood. In this study, the radioprotective effects of Dragon's blood were examined after whole brain irradiation of rats with either 100 MeV/u Carbon (12)C(6+) heavy ions or (60)Co γ-rays. The amounts of radiation-induced oxidative stress, inflammatory cytokines and apoptosis in irradiated rat brains were compared with and without Dragon's blood treatment. Compared to the "irradiation only" control group, the Dragon's blood treatment group significantly decreased malondialdehyde and hydrogen peroxide levels, and increased superoxide dismutase activity and glutathione levels induced by oxidative stress in radiation exposed rats (P < 0.05). Dragon's blood also significantly reduced radiation-induced inflammatory cytokines of tumor necrosis factor-α, interferon-γ and interleukin-6 levels (P < 0.05) and inhibited hippocampal neuronal apoptosis in (60)Co γ-ray irradiated rats. Furthermore, Dragon's blood significantly increased expression of brain-derived neurophic factor and inhibited the expression of pro-apoptotic caspase 3 (P < 0.05-0.01). Finally, Dragon's blood significantly inhibited expression of the AP-1 transcription factor family members c-fos and c-jun proteins (P < 0.05-0.01). The results obtained here suggest that Dragon's blood has radioprotective properties in rat brains after both heavy ions and (60)Co γ-ray exposure.

[Contents and movement of phosphorus in soil of long term effluent irrigated land forest].

Treated sewage effluent from Rotorua City, New Zealand, has been spray-irrigated into Whakarewarewa Forest to minimize effluent-derived nitrogen (N) and phosphorus (P) entering Lake Rotorua. To assess the capacity of the ecosystem to assimilate the effluent derived nutrients, a long term field trial was established within the Rotorua land treatment system. The objective of this study was to determine the accumulation, redistribution and movement of P in the volcanic soil after 11 year effluent irrigation. The soil samples were analyzed. Soil pH, total phosphorus (TP), Olsen P, Mehlich-3 P(M3P), M3Ca and M3Mg had increased significantly (p < 0.05) in the top soil (0-10 cm) in all effluent treated plots compared with the control plots. Some significant increase had extended deeper soil layer (20-40cm) or much deeper soil layer. Most effluent-derived P had accumulated in top 40cm. Concentrations of soil Olsen P and M3P in the medium and high effluent treatments were over environmental threshold levels (Olsen P, 60 mg x kg(-1); M3P, 150 mg x kg(-1)) in the top 20 cm. The values of soil saturation ratio (M3PSR) show that it was nearly saturated of soil P sorption in top soil. It was suggested that there was a potential environment crisis for soil P to move downward with drainage water. Regular soil sampling and Olsen P measurement using 60 mg x kg(-1) as an environment threshold could provide a solution for monitoring the movement of P down the soil profile. Phosphorus saturation ratio index (M3PSR) calculated as the molar ratio of M3P to (M3Al + M3Fe) appeared to be inadequate as an indicator for downward movement of soil P in such land treatment system. A new Phosphorus saturation ratio index for this system will be one of future study work.

Lysine scanning mutagenesis delineates structural model of the nicotinic receptor ligand binding domain.

Nicotinic acetylcholine receptors (AChR) and their relatives mediate rapid chemical transmission throughout the nervous system, yet their atomic structures remain elusive. Here we use lysine scanning mutagenesis to determine the orientation of residue side chains toward core hydrophobic or surface hydrophilic environments and use this information to build a structural model of the ligand binding region of the AChR from adult human muscle. The resulting side-chain orientations allow assignment of residue equivalence between AChR subunits and an acetylcholine binding protein solved by x-ray crystallography, providing the foundation for homology modeling. The resulting structural model of the AChR provides a picture of the ACh binding site and predicts novel pairs of residues that stabilize subunit interfaces. The overall results suggest that lysine scanning can provide the basis for structural modeling of other members of the AChR superfamily as well as of other proteins with repeating structures delimiting a hydrophobic core.