Beneficial Effect of Eucommia Polysaccharides on Systemic Lupus Erythematosus-like Syndrome Induced by Campylobacter jejuni in BALB/c Mice

The stem bark of Eucommia ulmoides Oliv. is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia in traditional Chinese medicine. This study was to determine whether the crude polysaccharides (EUPs) isolated from the stem bark of E. ulmoides had beneficial effects on lupus-like syndrome in mice. BALB/c mice were immunized with CJ-S₁₃₁ in Freund’s complete adjuvant on day 0, and then boosted on day 14. EUPs 15 or 30 mg kg⁻¹·day⁻¹, or prednisone 5 mg kg⁻¹·day⁻¹ was given to BALB/c mice intragastrically from day 0 to 34. Treatment with EUPs 15 or 30 mg kg⁻¹·day⁻¹ for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. These findings suggested that Eucommia polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndrome induced by CJ-S₁₃₁ in BALB/c mice.     

南五味子属药用植物的化学成分及其生物活性

综述了自上世纪90年代初以来对五味子科南五味子属药用植物的化学成分及其生物活性的研究工作。我们从5种南五味子属药用植物的藤茎中共分离鉴定了80余种化合物,并主要探讨了这些化合物的抗脂质过氧化、钙拮抗和PAF拮抗等与补血活血作用相关的生物活性,同时也尝试抗HIV方面的研究工作,发现部分木脂素和三萜类化学成分具有显著的生物活性。     

山豆根中黄酮类成分的LC／MS定性分析与HPLC含量测定

目的：建立山豆根中黄酮类成分的定性、定量分析方法,完善药材质量控制手段。方法：以HPLC—DAD—ESI—MS方法,对山豆根中黄酮类成分进行在线分离与定性鉴定;以HPLC方法同时测定山豆根药材中5个主要活性黄酮的含量。结果：从山豆根中共鉴定了17个黄酮成分,其中7个成分的保留时间、紫外吸收特征和质谱碎片与对照品一致,分别是三叶豆紫檀苷、槲皮素、芒柄花素、高丽槐素、苦参酮、山豆根酮和山豆根色烯素;另外根据紫外吸收特征和质谱碎片并结合文献数据初步确定了10个成分的化学结构。建立了山豆根中三叶豆紫檀苷、槲皮素、高丽槐素、山豆根酮和山豆根色烯素等5个黄酮类成分的回归方程,线性关系均良好（r〉0．9998）,加样回收率为96．40％-104．43％,采用此方法成功检测了17个山豆根样品中上述5种黄酮成分的含量。结论：本文建立的方法可定性、定号分析山豆根中的黄酮类成分．可用于山豆根药材的庸号分析．     

Quinolizidine alkaloids with anti-HBV activity from Sophora tonkinensis

A new matrine-type alkaloid, (-)-14 beta-hydroxyoxymatrine (1), was isolated from the roots and rhizomes of Sophora tonkinensis Gapnep. (Leguminosae), together with five known matrine-type alkaloids, (-)-14 beta-hydroxymatrine (2), (+)-oxymatrine (3), (+)-matrine (4), (+)-sophoranol (5), and (-)-5 alpha-hydroxysophocarpine ( 6), as well as with two known cytisine-type alkaloids, (-)-cytisine (7) and (-)- N-methylcytisine (8). Their structures were elucidated by spectroscopic methods. Compounds 1, 5 and 7 showed potent anti-HBV activity with an inhibitory potency against HBsAg secretion of 22.6 %, 31.1 % and 33.2 %, and against HBeAg secretion of 30.4 %, 26.3 % and 27.8 %, respectively.     

Prevention and treatment of gastrointestinal dysfunction following severe burns： A summary of recent 30-year clinical experience

AIM： To sum up the recent 30-year experience in the prevention and treatment of gastrointestinal dysfunction in severe burn patients, and propose practicable guidelines for the prevention and treatment of gastrointestinal （GI） dysfunction. METHODS： From 1980 to 2007, a total of 219 patients with large area and extraordinarily large area burns （LAB） were admitted, who were classified into three stages according the therapeutic protocols used at the time： Stage 1 from 1980 to 1989, stage 2 from 1990 to 1995, and stage 3 from 1996 to 2007. The occurrence and mortality of GI dysfunction in patients of the three stages were calculated and the main causes were analyzed. RESULTS： The occurrence of stress ulcer in patients with LAB was 8.6% in stage 1, which was significantly Dower than that in stage 1 （P 〈 0.05）. No massive hemorrhage from severe stress ulcer and enterogenic infections occurred in stages 2 and 3. The occurrence of abdominal distension and stress ulcer and the mortality in stage 3 patients with extraordinarily LAB was 7.1%, 21.4% and 28.5%, respectively, which were significantly lower than those in stage 1 patients （P 〈 0.05 or P 〈 0.01）, and the occurrence of stress ulcer was also significantly lower than that in stage 2 patients （P 〈 0.05）. CONCLUSION： Comprehensive fluid resuscitation, early excision of necrotic tissue, staged food ingestion, and administration of specific nutrients are essential strategies for preventing gastrointestinal complications and lowering mortality in severely burned patients.     

异型南五味子丁素、五味子酚和(+)-安五脂素对血小板聚集的影响

目的 观察3木脂素类成分：异型南五味子丁素(haeteroclitin D,HD)、五味子酚(schisanhenol,SAL)和( )-安五脂素[( )-anwulignan,AN]对血小板聚集的影响。方法 采用Born比浊法,观察此3种木脂素在0．05～25mg/L时对腺苷二磷酸(adenosine diphosphate,ADP)和血小板活化因子(platelet activating factor,PAF)诱导的兔血小板1、3、5min聚集率和最大聚集率以及最大聚集时间的影响。结果 ①HD和SAL可呈剂量依赖性抑制ADP和PAF诱导的血小板最大聚集率,AN的抑制作用较弱。②对ADP诱导的血小板1、3、5min聚集率,HD和SAL均可全程稳定抑制,AN5mg／L在3、5min时有较明显的抑制作用;对PAF诱导的血小板1、3、5min聚集率,HD在1、3min时抑制作用较强,SAL在3、5min时抑制作用较强。③HD、SAL,和AN对ADP和PAF诱导的血小板最大聚集时间无明显影响。结论 HD、SAL和AN在离体水平可不同程度抑制ADP和PAF诱导的兔血小板聚集。HD的抑制作用最强,可视为南五味子属药用植物的重要活性成分之一。     

Integrating transcriptomes and somatic mutations to identify RNA methylation regulators as a prognostic marker in hepatocellular carcinoma

Background:RNA methylation modifying plays an important role in the occurrence and progression of a range of human cancers including hepatocellular carcinoma(HCC),which is characterized by a mass of genetic and epigenetic alterations.However,the treatment targeting these alterations is limited.Methods:We used comprehensive bioinformatics analysis to analyze the correlation between cancerassociated RNA methylation regulators and HCC malignant features in network datasets.Results:We identified two HCC subgroups(cluster 1 and 2),which had clearly distinct clinicopathological,biofunctional and prognostic characteristics,by consensus clustering.The cluster 2 subgroup correlated with malignancy of the primary tumor,higher tumor stage,higher histopathological grade and higher frequency of TP53 mutation,as well as with shorter survival when compared with cluster 1.Gene enrichment indicated that the cluster 2 correlated to the tumor malignancy signaling and biological processes.Based on these findings,an 11-gene risk signature was built,which not only was an independent prognostic marker but also had an excellent power to predict the tumor features.Conclusions:Our study indicated that RNA methylation regulators are vital for HCC malignant progression and provide an important evidence for RNA methylation,methylation regulators are actionable targets for anticancer drug discovery.     

Uric acid enhances T cell immune responses to hepatitis B surface antigen-pulsed-dendritic cells in mice

AIMTo study the induction of T cellular immune responses in BALB/c mice immunized with uric acid and dendritic cells(DCs)pulsed with hepatitis B virus surface antigen(HBsAg).METHODSDCs were generated from bone-marrow cells of BABL/c mice,and then pulsed or unpulsed with HBsAg protein(HBsAg-pulsed-DCs or unpulsed-DCs)in vitro.BABL/c mice were immunized with HBsAg-pulsed-DCs(1×106)and uric acid,injected through the tail vein of each mouse.The mice in control groups were immunized with HBsAg-pulsed-DCs alone,unpulsed-DCs alone or 200 μg uric acid alone or PBS alone.The immunization was repeated 7 d later.Cytotoxic T lymphocytes(CTLs)/n vivo were determined by the CFSE labeled spleen lysis assay.Spleen cells or spleen T cells were isolated,and re-stimulated in vitro with HBsAg for 120 h or 72 h.Production of IFN-γ and IL-4 secreted by spleen cells were determined by ELISA method;proliferation of spleen T cells were detected by flow cytometry.RESULTSThe cytotoxicities of HBsAg-specific-CTLs,generated after immunization of HBsAg-pulsed-DCs and uric acid,were 68.63% ± 11.32% and significantly stronger than that in the control groups(P ＜ 0.01).Compared with control groups,in mice treated with uric acid and HBsAg-pulsed-DCs,the spleen T cell proliferation to HBsAg re-stimulation was stronger(1.34 ± 0.093 vs 1.081 ± 0.028,P ＜ 0.01),the level of IFN-γsecreted by splenocytes was higher(266.575 ± 51.323 vs 135.223 ± 32.563,P ＜ 0.01),and IL-4 level was lower(22.385 ± 2.252 vs 40.598 ± 4.218,P ＜ 0.01).CONCLUSIONUric acid can strongly enhance T cell immune responses induced by HBsAg-pulsed-DCs vaccine.Uric acid may serve as an effective adjuvant of DC vaccine against HBV infection.     

p38 mitogen-activated protein kinase inhibition attenuates burn-induced liver injury in rats

This study was made to evaluate the effect of SB203580, a specific p38 MAP kinase inhibitor, on burn-induced hepatic injury as well as the activation of nuclear factor (NF)-kappaB in severely burned rats. Sprague-Dawley rats were divided into three groups: (1) sham group, rats underwent sham burn; (2) burn group, rats given third-degree burns over 30% total body surface area (TBSA) and treated with vehicle plus lactated Ringer solution for resuscitation 4 ml/(kg% TBSA); and (3) burn plus SB203580 group, rats given burn injury and fluid resuscitation plus SB203580 (10 mg/kg i.v., 15 min and 12 h after burn). Hepatocellular injury (measured by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and hepatocellular function (determined by the indocyanine green dye retention rate (ICG R15)) were assessed at 24 h post-burn. Liver histologic changes were also analyzed. Burn trauma resulted in increased serum aminotransferases concentrations, decreased ICG R15, elevated serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels and hepatic TNF-alpha and IL-1beta mRNA expressions, and worsen histologic condition. The level of Nuclear Factor (kappa) inhibitor (IkappaBalpha) in liver was decreased and DNA-binding activity of Nuclear Factor-kappaB (NF-kappaB) was increased after thermal injury. p38 MAP kinase was more significantly activated in liver harvested from burn rats than from shams. SB203580 inhibited the activation of p38 MAP kinase, reduced the levels of TNF-alpha and IL-1beta, and prevented burn-mediated liver injury. Both the IkappaBalpha level and NF-kappaB activity in the liver following burns was not affected by administration with SB203580. These findings suggest that (1) p38 MAP kinase activation is one important aspect of the signaling event that may mediate the release of TNF-alpha and IL-1beta and contributes to burn-induced liver injury and (2) p38 MAP kinase does not influence the activation of NF-kappaB directly in the liver of severely burned rats.     

Macrophage immunomodulatory activity of the polysaccharides from the roots of Bupleurum smithii var. parvifolium

Aim of the study

Radix Bupleuri, one of the most frequently prescribed crude herbs in traditional Chinese medicine, has been used for centuries to treat inflammatory diseases. However, little is known about the therapeutic mechanisms of crude polysaccharides (BPs) isolated from the roots of Bupleurum smithii var. parvifolium. Macrophages play important roles in inflammatory diseases such as systemic lupus erythematosus (SLE). The purpose of the present work was to investigate immunomodulative effects of Bupleurum polysaccharides on murine peritoneal macrophages.

Materials and methods

BALB/c mice were administered intragastrically with Bupleurum polysaccharides 20, 40, and 80 mg kg⁻¹ day⁻¹, or prednisone 3 mg kg⁻¹ day⁻¹ or levamisole 25 mg kg⁻¹ day⁻¹ from day 0 to day 6. Peritoneal macrophages were isolated 5 days after intraperitoneal injection of 1 mL 5% sodium thioglycollate. Phagocytic functions of macrophages were studied; cytokines concentrations in the culture supernatants were determined by enzyme-linked immunosorbent assay and the secretion of nitric oxide (NO) was quantified by Griess reaction.

Results

Treatment with BPs enhanced phagocytic functions of macrophages (phagocytosis of apoptotic thymocytes, IgG-opsonized sheep red blood cells and chicken red blood cells) and inhibited LPS-induced productions of NO and proinflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α).

Conclusions

Bupleurum polysaccharides up-regulated phagocytic activities but inhibited LPS-induced productions of proinflammatory mediators. These data suggested that at least part of the traditional beneficial effects of Bupleurum on inflammatory diseases could be ascribed to the immunomodulatory effects of Bupleurum polysaccharides on macrophages.