Proliferatins suppress lipopolysaccharide-induced inflammation via inhibition of the NF-κB and MAPK signaling pathways.

Three previously undescribed polyketides [proliferatin A-C (1-3)] with anti-inflammatory activity were isolated from Fusarium proliferatum. 1-3 attenuated the production of inflammatory signal messengers including nitric oxide (NO), reactive oxygen species, proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), as well as the related proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the potential anti-inflammatory mechanism of 1-3 involved in the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinases (MAPKs) signaling pathways. Experimental evaluation of the protein levels revealed that 1-3 can inhibit the phosphorylation of IκB kinase (IKK), the degradation of NF-κB Inhibitor-α (IκBα), the phosphorylation of nuclear factor-κB (NF-κB) and can reduce NF-κB transportation to the nucleus. Interestingly, 1-3 decreased the phosphorylation of MAPKs including p-p38, p-ERK, and p-JNK. Molecular docking models suggest that binding of 1-3 to TLR4-MD-2 complex may lead to inhibition of NF-κB and MAPK signaling pathways, which was confirmed in vitro by surface plasmon resonance (SPR) assays. 1-3 can thus constitute potential therapeutic candidates for the treatment of inflammation-associated diseases.

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis.

Background: Excessive inflammation results in severe tissue damage as well as serious acute or chronic disorders, and extensive research has focused on finding new anti-inflammatory hit compounds with safety and efficacy profiles from natural products. As promising therapeutic entities for the treatment of inflammation-related diseases, fusaproliferin and its analogs have attracted great interest. However, the underlying anti-inflammatory mechanism is still poorly understood and deserves to be further investigated. Methods: For the estimation of the anti-inflammatory activity of fusaproliferin (1) and its analogs (2-4) in vitro and in vivo, lipopolysaccharide (LPS)-induced RAW264.7 macrophages and zebrafish embryos were employed. Then, transcriptome analysis was applied to guide subsequent western blot analysis of critical proteins in related signaling pathways. Surface plasmon resonance assays (SPR) combined with molecular docking analyses were finally applied to evaluate the affinity interactions between 1-4 and TLR4 and provide a possible interpretation of the downregulation of related signaling pathways. Results: 1-4 significantly attenuated the production of inflammatory messengers, including nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), as well as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the ability of compound 1 to reverse LPS stimulation and the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPKs) signaling pathways contribute to the anti-inflammatory process. Experimental verification at the protein level revealed that 1 can inhibit the activation of inhibitor of NF-κB kinase (IKK), degradation of inhibitor of NF-κB (IκB), and phosphorylation of NF-κB and reduce nuclear translocation of NF-κB. 1 also decreased the phosphorylation of MAPKs, including p38, extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK). SPR assays and molecular docking results indicated that 1-4 exhibited affinity for the TLR4 protein with KD values of 23.5-29.3 µM. Conclusion: Fusaproliferin and its analogs can be hit compounds for the treatment of inflammation-associated diseases.

Aureonitol Analogues and Orsellinic Acid Esters Isolated from Chaetomium elatum and Their Antineuroinflammatory Activity.

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1ß, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.

First report of macrolide resistance gene erm(T) harbored by a novel small plasmid from Erysipelothrix rhusiopathiae.

The macrolide resistance gene erm(T) was identified for the first time in a porcine Erysipelothrix rhusiopathiae isolate from swine in China. The novel 3,749-bp small plasmid pER29, which carries erm(T), had a G+C content of 31% and four distinct open reading frames. The presence of pER29 increased by at least 128-fold the MICs of clindamycin and erythromycin for E. rhusiopathiae. The fitness cost of pER29 could be responsible for the low frequency of erm(T) in E. rhusiopathiae.

Efficacy evaluation on flexible dozes of Pregabalin for treatment of peripheral neuropathy in refrac- tory painful diabetics / 上海预防医学

Objective ] To evaluate the efficacy and tolerability of a flexible-dose pregabalin regimen in patients with refractory painful diabetic peripheral neuropathy . [ Methods] A prospective, open, non-randomized design was adopted .A series of 48 patients with refractory painful diabetic peripheral neuropathy received pregabalin 150 to 300 mg/d for 4 weeks.Pain intensity and sleep interference score were measured using numerical rating scale at baseline and at 2 and 4 weeks after therapy.Secondary meas-ures for assessment of mood and overall efficacy included 17-item Hamilton depression scale ( HAMD -17), Hamilton anxiety scale ( HAMA) and patient global impression of change ( PGIC).Adverse events were recorded . [ Results] The 46 patients completed the 4 weeks study .The mean dose of pregabalin was (262.5 ±57.9)mg/d at endpoint.The mean pain score decreased from 6.2 ±1.0 at baseline to 4.3 ± 1.4 at 2 weeks and 3.0 ±1.6 at 4 weeks ( P all <0.01).The mean sleep interference score was 5.1 ±1.4, 3.3 ±1.4, 2.1 ±1.5 respectively (P all <0.01).Also, significant improvements were noted in the HAMD and HAMA score (P<0.01).And among them, 26 patients (56.5%) reported“very much improved” or“much improved” in PGIC.Pregabalin was generally well tolerated without severe side effects reported and only 2 patients ( 4 .2%) discontinued the study because of their dizziness , somnolence . [ Conclusion] Pregabalin 150 to 300 mg/d can effectively improve pain , sleep, anxiety/depression in patients with refractory painful diabetic peripheral neuropathy , and it was well-tolerated.

Seasonal influence on the diagnosis of food allergy in children less than 3 years of age / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the seasonal influence on the diagnosis of food allergy in children under 3 years of age.</p><p><b>METHOD</b>The data of epidemiological studies about food allergy of children under 3 years of age attending routine well-baby checks at the Department of Primary Child Care, Children's Hospital of Chongqing Medical University in the winter and summer, 2009, including questionnaires, results of skin prick test (SPT), food elimination and oral food challenge (OFC) were analyzed. All the data were analyzed by SPSS 17.0.</p><p><b>RESULT</b>The age and sex distribution, and both the rates of the drop-out in two studies were similar. Ninety infants were positive for SPT, 40 infants were positive for OFC, and 31 infants dropped out in winter; while 65 infants were positive for SPT, 25 positive for OFC, and 31 dropped out in summer. The percentage of positive SPT in the children performed in winter was higher than that in summer (14.9%, 90/603 vs 10.7%, 65/607) (P = 0.028). Skin prick test accuracy was similar when the studies were performed in winter and in summer [sensitivity 0.85 and 0.84, positive predictive value (PPV) 0.54 and 0.47, negative predictive value (NPV) 0.99 and 0.99]. The prevalence of food allergy in the children studied in winter was higher than that in summer (7.0% vs 4.3%), but the difference was not significant. After correcting the prevalence for dropout children, the prevalence of food allergy (FA) investigated in winter was significantly higher than that in summer (9.3% vs 5.9%). The results of circular distribution analysis showed the date of birth corresponding to estimated value of peak point of SPT in winter were not consistent with it in summer, so was OFC. Either the results of skin prick test or oral food challenge in two studies were not correlated with the seasons of birth.</p><p><b>CONCLUSION</b>Our data showed that the rates of positive SPT and the prevalence of food allergy were correlated with the seasons, but the seasons of birth did not influence the results of skin prick test or oral food challenge in children, while the real age of children were related to them.</p>

[Extraction and purification of the Klebsiella pneumoniae capsular polysaccharide and the effection on the cell immunoactivity].

Klebsiella pneumoniae was cultured followed by the preparation and immunoactivity elucidating of its polysaccharide (CPS). The lysis of cell is the first key step in the preparation, under the co-action of trypsin, lysozyme and NP-40, the cell lysed within 2h, then the lysate was concentrated by ultrafiltration which serves as concentrating and partial purifying action simultaneously. Crude CPS was got by ethanol precipitation, then purified through the Ion-exchange and gel filtration, the purity of CPS was judged by the gel filtration and agarose gel electrophoresis. The effect of CPS on the cell immunoactivity was studied in detail, the results show that CPS possesses bidirectional immunoregulation on the spleen cells of mice, that is, low concentration of CPS can stimulate the immune response while the high concentration manifests the inhibition significantly. The investigation results will benefit on the exploitation of the CPS.

Analysis of Surveillance of Birth Defect on Perinatal Fetuses in Hubei Province during 2001-2005 / 实用儿科临床杂志

Objective To analyze the prevalence and factors of birth defect on perinatal fetuses in Hubei province.Method The prevalence of birth defect on perinatal fetuses delivered in 28 weeks or more was analyzed in Hubei surveillance hospital of birth defect during 2001-2005 year.Results The prevalence rate of birth defect on perinatal feruses from 2001 to 2005 year was 107.39 per 10 000,and increased significantly than that in 2001 year 81.07 per 10 000(?2=39.505 P