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This research aims to investigate the impact of Didang decoction (DD) on the formation of neutrophil extracellular traps (NETs) and cancer-associated thrombosis in lung cancer. BALB/c nude mice were used to establish xenograft models for inducing deep vein thrombosis. Tumor growth and thrombus length were assessed. The impact of DD on NET generation was analyzed using enzyme-linked immunosorbent assay, immunofluorescence staining, quantitative real-time PCR, and western blot analysis, both in vivo and in vitro. CI-amidine, a PAD4 inhibitor, was employed to evaluate the role of PAD4 in the generation of NETs. In vivo studies demonstrated that treatment with DD reduced tumor growth, inhibited thrombus formation, and decreased the levels of NET markers in the serum, tumor tissues, neutrophils, and thrombus tissues of mice. Additional data indicated that DD could suppress neutrophil counts, the release of tissue factor (TF), and the activation of thrombin-activated platelets, all of which contributed to increased formation of NETs in mouse models. In vitro, following incubation with conditioned medium (CM) derived from Lewis lung carcinoma cells, the expression of NET markers in neutrophils was significantly elevated, and an extracellular fibrous network structure was observed. Nevertheless, these NET-associated changes were partially counteracted by DD. Additionally, CI-amidine reduced the expression of NET markers in CM-treated neutrophils, consistent with the effects of DD. Collectively, DD inhibits cancer-associated thrombosis in lung cancer by decreasing PAD4-dependent NET formation through the regulation of TF-mediated thrombin-platelet activation. This presents a promising therapeutic strategy for preventing and treating venous thromboembolism in lung cancer., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, demonstrated an overall response rate of 63.0% in 165 heavily pretreated patients with relapsed or refractory multiple myeloma in the phase 1/2 MajesTEC-1 study. Cytokine release syndrome (CRS), a known manifestation of T-cell redirection, was observed in 119 of 165 patients (72.1%)., Methods: Patients received once-weekly teclistamab 1.5 mg/kg subcutaneously after two step-up doses (0.06 and 0.3 mg/kg). CRS was graded according to American Society for Transplantation and Cellular Therapy criteria and managed according to the study protocol, including use of tocilizumab and/or steroids., Results: Most cases of CRS occurred during the step-up dosing schedule of teclistamab and were grade 1 (50.3% of patients) or grade 2 (21.2% of patients); a single case of grade 3 CRS was reported in a patient with concurrent grade 3 pneumonia. All CRS cases resolved and none led to treatment discontinuation. Overall, 33.3% of patients had >1 CRS event; CRS recurrence was reduced when tocilizumab was administered for the first CRS event compared with when it was not (20.0% vs. 62.2%, respectively). Baseline characteristics such as tumor burden and cytokine levels did not appear to predict CRS incidence or severity., Conclusions: Findings of this study support the need for preemptive planning and prompt management of CRS in patients treated with T-cell-engaging bispecific antibodies. Intervention with tocilizumab for CRS appears to decrease the likelihood of patients experiencing subsequent CRS events without compromising response to teclistamab., Plain Language Summary: Cytokine release syndrome (CRS), observed in 72.1% of patients treated with teclistamab in the MajesTEC-1 study, was mostly grade 1 or 2 and manageable, without requiring treatment discontinuation. Most CRS occurred during the step-up schedule, requiring vigilance during treatment initiation. Ensure fever is resolved and patients have no signs of infection before initiating the teclistamab step-up schedule or administering the next teclistamab dose, to avoid exacerbating CRS. Tocilizumab reduced the risk of subsequent CRS in patients receiving it for their first CRS event (20.0% vs. 62.2% in those not receiving it), without affecting response to teclistamab. No baseline characteristics, including tumor burden or cytokine levels, appeared to clearly predict for CRS occurrence or severity., (© 2023 Janssen Pharmaceuticals. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Introduction: Dandelion (Taraxacum mongolicum Hand.-Mazz.) is a perennial herb with diverse pharmacological effects. The development and utilization of dandelion have attracted much attention., Objectives: Our aims were to provide a reference basis for the identification of the origin of dandelions and to study the influence of their origin on their quality. Methods High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze metabolites from dandelions from four different geographical regions in China, namely Gansu, Henan, Shanxi, and Jiangsu. Metabolite analysis was performed using orthogonal partial least-squares discriminant analysis, and to identify potential metabolic pathways, MBRole was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis., Results: Principal component analysis revealed that the chemical components of dandelions sampled from the four regions showed noticeable differences. Twenty-six, six, six, eight, eight, and fifteen differentially produced metabolites were identified upon comparison between Gansu and Jiangsu, Gansu and Shanxi, Gansu and Henan, Henan and Shanxi, Henan and Jiangsu, and Shanxi and Jiangsu, respectively. These differentially produced metabolites were mainly phenolic compounds. Further, KEGG pathway enrichment analysis showed that the main metabolic pathways involved were biosynthesis of phenylpropanoids and flavonoids., Conclusion: The methods reported herein can be used to identify the origin of dandelions; moreover, our results can serve as a reference basis for future studies., (© 2021 John Wiley & Sons, Ltd.)

Among the various gynaecological cancers, ovarian cancer (OC) is the third most severe cancer worldwide affecting women. Syringic acid (SRA) exhibits several hypoglycaemia, antioxidant, and anti-inflammatory properties. The study aimed to examine the proapoptotic activities of SRA on OC in PA-1 cells. SRA has been shown to decrease cell viability, increase the rate of cell apoptosis, and cause mitochondrial membrane potential to dissipate and induce over-accumulation of intracellular reactive oxygen species in PA-1 cells after 24 h of exposure. We examined the anticancer efficacy of SRA with its responsible molecular mechanism in the PA-1 cell lines of human OC. In a dose-dependent manner, SRA substantially suppressed cell proliferation and migration. SRA exhibited significant downregulation of cyclins including CDK2, CDK4, and Cyclin D1 responsible for cell-cycle regulation. The apoptosis-mediated anticancer activity was mainly mediated through caspase-3, caspase-8, caspase-9 and Bax upregulation, and Bcl-2 downregulation. We report that SRA significantly inhibits the expression of signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase (JNK), P65, and protein kinase B (AKT) pathways. These findings depict the effective inhibition of STAT3, p38, and AKT expression by SRA, making it a potential therapeutic candidate for human OC., (© 2021 Wiley Periodicals LLC.)

The incidence of ulcerative colitis (UC) is increasing in recent years. The protective effect of cryptotanshinone, a natural compound from Salvia miltiorrhiza Bunge, on UC was investigated both in vivo and in vitro models. UC model was established by dextran sulfate sodium administration in drinking water and cryptotanshinone was orally administrated. RAW264.7 cells were stimulated by lipopolysaccharide (LPS) with or without cryptotanshinone pretreatment. The body weights and disease activity index (DAI) were recorded. The pathological alterations were evaluated by H&E staining. The levels of pro-inflammatory cytokines in colon tissues and cell culture medium were determined with enzyme-linked immune sorbent assay (ELISA) kits. The protein expression was detected by Western blotting and immunohistochemistry. Results showed that cryptotanshinone significantly increased the body weight and colon length, reduced the score of DAI, and improved pathological changes. Furthermore, the expression of inducible nitric oxide synthase, cyclooxygenase-2, receptor-interacting protein kinase 3, NF-κB p65 and the secretion of tumor necrosis factor-α, IL-6 in colon tissues and LPS-stimulated cells were significantly inhibited by cryptotanshinone. Besides, cryptotanshinone significantly inhibited LPS-triggered toll-like receptor 4 luciferase reporter activity with an IC 50 at 7.2 μM. In conclusion, cryptotanshinone ameliorated experimental UC possibly by inhibiting intestinal inflammation., (© 2020 John Wiley & Sons, Ltd.)

Background: Osteosarcoma (OS) is one of the most common malignant bone tumors. It is essential to explore early diagnostic indicators with high sensitivity and specificity due to the rapid progression and metastasis of OS and the poor survival of metastatic OS patients. However, a few indicators of diagnostic significance have been described., Methods: A total of 458 OS patients, 312 healthy individuals, and 228 patients with primary benign bone lesions were included. Logistic regression was performed on 46 clinical laboratory parameters to establish the diagnostic classifiers, which were evaluated by analysis of the receiver operating characteristic (ROC) curves., Results: We established three diagnostic classifiers, called C os for all ages, C los for low ages, and C hos for high ages, with clinical laboratory parameters to distinguish OS from healthy individuals. All classifiers showed better diagnostic performances than alkaline phosphatase (ALP) in the independent validation cohort. In addition, these classifiers had better ability than ALP to discriminate OS from primary benign bone lesions. Furthermore, C os , C los, and C hos had larger AUC than ALP to identify small-size and early-stage OS and could also detect ALP-negative OS effectively., Conclusion: Our study suggests the potential of C os , C los , and C hos as non-invasive biomarkers for early OS., (© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Sarsasapogenin-AA13(AA13), a sarsasapogenin derivative, exhibited good neuroprotective and anti-inflammatory activities in vitro and therapeutic effects on learning and memory dysfunction in amyloid-β-injected mice. A sensitive UPLC-MS/MS method was developed and validated to quantitatively determine AA13 in rat plasma and was further applied to evaluate the pharmacokinetic behaviour of AA13 in rats that were administered AA13 intravenously and orally. This method was validated to exhibit excellent linearity in the concentration range of 1-1000 ng/mL. The lower limit of quantification was 1 ng/mL for AA13 in rat plasma. Intra-day accuracy for AA13 was in the range of 90-114%, and inter-day accuracy was in the range of 97-103 %. The relative standard deviation of intra-day and inter-day assay was less than 15%. After a single oral administration of AA13 at the dose of 25 mg/kg, C max of AA13 was 1266.4 ± 316.1 ng/mL. AUC 0-48 h was 6928.5 ± 1990.1 h·ng/mL, and t 1/2 was 10.2 ± 0.8 h. Under intravenous administration of AA13 at a dosage of 250 μg/kg, AUC 0-48 h was 785.7 ± 103.3 h⋅ng/mL, and t 1/2 was 20.8 ± 7.2 h. Based on the results, oral bioavailability (F %) of AA13 in rats at 25 mg/kg was 8.82 %., (© 2019 John Wiley & Sons, Ltd.)

Background and Purpose: Several clinical trials have demonstrated that dual antiplatelet therapy (DAPT) benefited patients with transient ischaemic attack (TIA) with an ABCD2 score ≥4. The present study aimed to investigate whether the ABCD3-I score could be a more appropriate tool for selection of patients with TIA to receive DAPT in real-world settings., Methods: We derived data from the TIA database of The First Affiliated Hospital of Zhengzhou University. The predictive outcome was ischaemic stroke at 90 days. The additive interaction effect was presented by the attributable proportion due to interaction. Kaplan-Meier curves were plotted to present cumulative stroke rates in different risk categories with monotherapy and DAPT. Cox proportional hazards regression was used to determine risk factors associated with stroke., Results: Among 785 patients, the mean (SD) age was 56.95 (12.73) years and 77 patients (9.8%) had an ischaemic stroke at 90 days. A total of 55.8% of patients (attributable proportion due to interaction; 95% confidence interval, 20.8%-90.9%) were attributed to additive interaction of ABCD3-I score and antiplatelet therapy. Kaplan-Meier curves showed a significant difference between patients receiving monotherapy and DAPT in high-risk patients with TIA (P = 0.021). DAPT reduced 90-day stroke risk in high-risk patients with TIA as assessed independently by ABCD3-I score (adjusted hazard ratio, 0.43; 95% confidence interval, 0.20-0.92, P = 0.031). The benefit did not exist in low- and medium-risk patients by ABCD3-I score (patients with ABCD2 score ≥ 4 or <4)., Conclusions: High-risk patients with TIA assessed by ABCD3-I score received the most pronounced clinical benefit from early use of DAPT in real-world clinical experience., (© 2018 EAN.)

A sarsasapogenin derivative, sarsasapogenin-AA22 (AA22), with cyclobutylamine at the 3-hydroxyl position of sarsasapogenin, has great neuroprotective activity in PC12 cells and NO production inhibitory activity in RAW264.7 cell lines. A method was developed to determine AA22 in rat plasma which was further applied to evaluate the pharmacokinetics of AA22 after taking a single dose of AA22. Liquid chromatography tandem mass spectrometry was used in the method, while diosgenin was used as internal standard. A simple protein precipitation based on acetonitrile was utilized. A simple sample cleanup promoted the throughput of the method considerably. The method was validated over the range of 1-1000 ng/mL with a correlation coefficient > 0.99. The lower limit of quantification was 1 ng/mL for AA22 in plasma. Intra- and inter-day accuracies for AA22 were 92-111 and 100-103%, respectively, and the inter-day precision was <15%. After a single oral dose of 25 mg/kg of AA22, the mean peak plasma concentration of AA22 was 2114 ± 362 ng/mL at 6 h. The area under the plasma concentration-time curve was 196,098 ± 69,375 h ng/mL, and the elimination half-life was 8.7 ± 2.2 h., (Copyright © 2018 John Wiley & Sons, Ltd.)

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in the liver and induces oxidative stress and inflammation. Melatonin possesses potent hepatoprotective properties against the development and progression of acute and chronic liver injury. Nevertheless, the molecular mechanism underlying the protective effects of melatonin against Cd-induced hepatotoxicity remains obscure. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver inflammation and hepatocyte death. Male C57BL/6 mice were intraperitoneally injected with melatonin (10 mg/kg) once a day for 3 days before exposure to CdCl 2 (2.0 mg/kg). We found that Cd induced hepatocellular damage and inflammatory infiltration as well as increased serum ALT/AST enzymes. In addition, we showed that Cd triggered an inflammatory cell death, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Moreover, melatonin treatment significantly alleviated Cd-induced liver injury by decreasing serum ALT/AST levels, suppressing pro-inflammatory cytokine production, inhibiting NLRP3 inflammasome activation, ameliorating oxidative stress, and attenuating hepatocyte death. Most importantly, melatonin markedly abrogated Cd-induced TXNIP overexpression and decreased the interaction between TXNIP and NLRP3 in vivo and in vitro. However, treatment with siRNA targeting TXNIP blocked the protective effects of melatonin in Cd-treated primary hepatocytes. Collectively, our results suggest that melatonin confers protection against Cd-induced liver inflammation and hepatocyte death via inhibition of the TXNIP-NLRP3 inflammasome pathway., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The purpose of the study was to explore the individual, social and environmental factors influencing regular exercise on the basis of the theoretical framework of social ecological model among adults with type 2 diabetes and peripheral neuropathy. A total of 122 participants were chosen from Tianjin Metabolic Disease Hospital from November 2013 to May 2014. Information on exercise status and influencing factors was collected. Most participants took walking as the mode of exercise and exercised alone. Only 59.8% of participants were reported to carry out regular exercise. Logistic regression analysis suggested that being male, longer duration with diabetic peripheral neuropathy, higher self-efficacy for exercise and higher objective support were associated with regular exercise. Exercise status was clearly not ideal among adults with type 2 diabetes and peripheral neuropathy. The study highlighted the need to take measures to improve self-efficacy for exercise and social support in order to promote exercise participation among adults with type 2 diabetes and peripheral neuropathy., (© 2016 John Wiley & Sons Australia, Ltd.)

Background: Many studies have indicated that the reduced folate carrier gene (SLC19A1) is associated with an increased risk of neural tube defects (NTDs). However, the interaction between the SLC19A1 gene variant and maternal fever exposure and NTD risk remains unknown. The aim of this study was to investigate whether the risk for NTDs was influenced by the interactions between the SLC19A1 (rs1051266) variant and maternal first trimester fever., Methods: We investigated the potential interaction between maternal first trimester fever and maternal or offspring SLC19A1 polymorphism through a population-based case-control study. One hundred and four nuclear families with NTDs and 100 control families with nonmal newborns were included in the study. SLC19A1 polymorphism was determined using polymerase chain reaction-restricted fragment length polymorphism., Results: Mothers who had the GG/GA genotype and first trimester fever had an elevated risk of NTDs (adjusted odds ratio, 11.73; 95% confidence interval, 3.02-45.58) as compared to absence of maternal first trimester fever and AA genotype after adjusting for maternal education, paternal education, and age, and had a significant interactive coefficient (γ = 3.17) between maternal GG/GA genotype and first trimester fever. However, there was no interaction between offspring's GG/GA genotype and maternal first trimester fever (the interactive coefficient γ = 0.97) after adjusting for confounding factors., Conclusion: Our findings suggested that the risk of NTDs was potentially influenced by a gene-environment interaction between maternal SLC19A1 rs1051266 GG/GA genotype and first trimester fever. Maternal GG/GA genotype may strengthen the effect of maternal fever exposure on NTD risk in this Chinese population., (© 2014 Wiley Periodicals, Inc.)

The encounter of amateur science with synthetic biology has led to the formation of several amateur/do-it-yourself biology (DIYBio) groups worldwide. Although media outlets covered DIYBio events, most seemed only to highlight the hope, hype, and horror of what DIYBio would do in the future. Here, we analyze the European amateur biology movement to find out who they are, what they aim for and how they differ from US groups. We found that all groups are driven by a core leadership of (semi-)professional people who struggle with finding lab space and equipment. Regulations on genetic modification limit what groups can do. Differences between Europe and the US are found in the distinct regulatory environments and the European emphasis on bio-art. We conclude that DIYBio Europe has so far been a responsible and transparent citizen science movement with a solid user base that will continue to grow irrespective of media attention., (© 2014 The Authors. Bioessays published by WILEY Periodicals, Inc.)

Annexin 1, a glucocorticoid (GC)-inducible protein, can play an important role via formyl peptide receptor like 1 (FPR2/ALX, also known as FPRL1) in inflammatory pain modulation. The aim of this review is to analyze different lines of evidence for the role of ANXA1 with different mechanisms on inflammatory pain and describe the profile of ANXA1 as a potential analgesic. A Medline (PUBMED) search using the terms 'Annexin 1 distribution OR expression, FPR2/ALX distribution OR expression, Annexin 1 AND pain, Annexin 1 AND FPR2/ALX AND pain' was performed. Articles with a publication date up to Nov. 1st, 2012 were included. The antinociception of ANXA1 has been evaluated in diverse pain models. It has been suggested that ANXA1 may exerts its action via: (1) inhibiting vital cytokines involved in pain transmission, (2) inhibiting neutrophil accumulation through preventing transendothelial migration via an interaction with formyl peptide receptors, (3) facilitating tonic opioid release from neutrophil in inflammatory site, (4) interrupting the peripheral nociceptive transmission by suppressing neuronal excitability. In general, ANXA1 is a potential mediator for anti-nociception and the role with its receptor constitute attractive targets for developing anesthesia and analgesic drugs, and their interaction may prove to be a useful strategy to treat inflammatory pain., (© 2013 European Pain Federation - EFIC®)

A sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for determination of bakkenolide D (BD), which was further applied to assess the pharmacokinetics of BD. In the LC-MS/MS method, the multiple reaction monitoring mode was used and columbianadin was chosen as internal standard. The method was validated over the range of 1-800 ng/mL with a determination coefficient >0.999. The lower limit of quantification was 1 ng/mL in plasma. The intra- and inter-day accuracies for BD were 91-113 and 100-104%, respectively, and the inter-day precision was <15%. After a single oral dose of 10 mg/kg of BD, the mean peak plasma concentration of BD was 10.1 ± 9.8 ng/mL at 2 h. The area under the plasma concentration-time curve (AUC0-24 h ) was 72.1 ± 8.59 h ng/mL, and the elimination half-life (T1/2 ) was 11.8 ± 1.9 h. In case of intravenous administration of BD at a dosage of 1 mg/kg, the AUC0-24 h was 281 ± 98.4 h⋅ng/mL, and the T1/2 was 8.79 ± 0.63 h. Based on these results, the oral bioavailability of BD in rats at 10 mg/kg is 2.57%., (Copyright © 2013 John Wiley & Sons, Ltd.)

A sensitive rapid analytical method was established and validated to determine the bakkenolide A (BA) in rat plasma. This method was further applied to assess the pharmacokinetics of BA in rats receiving a single dose of BA. Liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode was used in the method, and costundide was used as internal standard. A simple protein precipitation based on methanol was employed. The combination of a simple sample cleanup and short chromatographic running time (2.4 min) increased the throughput of the method substantially. The method was validated over the range of 1-1000 ng/mL with a correlation coefficient > 0.99. The lower limit of quantification was 1 ng/mL for BA in plasma. Intra- and inter-day accuracies for BA were 93-112% and 103-104%, respectively, and the inter-day precision was less than 15%. After a single oral dose of 20 mg/kg of BA, the mean peak plasma concentration (C(max) ) of BA was 234.7 ± 161 ng/mL at 0.25 h. The area under the plasma concentration-time curve (AUC(0-24 h) ) was 535.8 ± 223.7 h·ng/mL, and the elimination half-life (T(1/2) ) was 5.0 ± 0.36 h. In case of intravenous administration of BA at a dosage of 2 mg/kg, the area under the plasma concentration-time curve (AUC(0-24 h) ) was 342 ± 98 h⋅ng/mL, and the elimination half-life (T(1/2) ) was 5.8 ± 0.7 h. Based on the results, the oral bioavailability of BA in rats at 20 mg/kg is 15.7%., (Copyright © 2012 John Wiley & Sons, Ltd.)

Furanodiene, a sesquiterpene component extracted from the essential oil of the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling (Wen Ezhu), is widely used in traditional Chinese medicine. A sensitive analytical method was established and validated for furanodiene in rat plasma, which was further applied to assess the pharmacokinetics of furanodiene in rats receiving a single dose of furanodiene. Liquid chromatography tandem mass spectrometry (LC/MS/MS) in multiple reaction monitoring mode was used in the method and costundide was used as internal standard. A simple protein precipitation based on methanol was employed. The simple sample cleanup increased the throughput of the method substantially. The method was validated over the range of 1-1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1 ng/mL for furanodiene in plasma. Intra- and inter-day accuracies for furanodiene were 88-115 and 102-107%, and the inter-day precision less than 14.4%. After a single oral dose of 10 mg/kg of furanodiene, the mean peak plasma concentration of furanodiene was 66.9 ± 23.4 ng/mL at 1 h, the area under the plasma concentration-time curve (AUC(0-10 h)) was 220 ± 47.8 h ng/mL, and the elimination half-life was 1.53 ± 0.06 h. After an intravenous adminstration of furanodiene at a dosage of 5 mg/kg, the area under the plasma concentration-time curve was 225 ± 76.1 h⋅ng/mL, and the elimination half-life was 2.40 ± 1.18 h. Based on this result, the oral bioavailability of furanodiene in rats at 10 mg/kg is 49.0%., (Copyright © 2011 John Wiley & Sons, Ltd.)

Endogenous cannabinoids and peripheral cannabinoid CB2 receptors (CB2Rs) are involved in the antinociceptive effect of electroacupuncture (EA) on inflammatory pain. However, it is not clear how CB2R activation contributes to the antinociceptive effect of EA. The major proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6, are involved in inflammatory pain. Here we determined the effects of CB2R activation and EA on the expression level of IL-1β, IL-6 and TNF-α in inflamed skin tissues. Inflammatory pain was induced by injection of complete Freund's adjuvant into the left hindpaw of rats. Thermal hyperalgesia was tested with a radiant heat stimulus, and mechanical allodynia was quantified using von Frey filaments. The mRNA and protein levels of IL-1β, IL-6 and TNF-α in inflamed skin tissues were measured using real-time polymerase chain reaction and Western blot, respectively. Local injection of the selective CB2R agonist AM1241 or EA applied to GB30 and GB34 significantly reduced thermal hyperalgesia and mechanical allodynia induced by tissue inflammation. The specific CB2R antagonist AM630 significantly attenuated the antinociceptive effect of EA. Furthermore, EA or AM1241 treatment significantly decreased the mRNA and protein levels of IL-1β, IL-6 and TNF-α in inflamed skin tissues. In addition, pretreatment with AM630 significantly reversed the inhibitory effect of EA on these cytokine levels in inflamed skin tissues. Our results suggest that EA reduces inflammatory pain and proinflammatory cytokines in inflamed skin tissues through activation of CB2Rs., (© 2011 European Federation of International Association for the Study of Pain Chapters.)

Nutritional intervention is effective in reducing the risk of neural tube defects (NTDs). To determine the effects of nutritional supplementation on human metabolism, a metabonomic study was carried out on 96 women of reproductive age. Subjects with nutritional intervention were given fortified wheat flour (containing folic acid, vitamin B₁, vitamin B₂, ferric sodium edetate and zinc oxide) for 8 months. Serum metabolic fingerprinting was detected via ultraperformance liquid chromatography in tandem with time-of-flight mass spectrometry (UPLC-TOF MS), and data acquired was processed by multivariate statistical analysis. The result revealed a significant difference between the control and intervention group. Twenty potential biomarkers, including fructose 6-phosphate, sphingosine 1-phosphate, docosahexaenoic acid and hexadecanoic acid, were located and identified by the accurate mass measurement of TOF MS. These compounds are believed to be functionally related to anti-oxidative competence in vivo. In conclusion, metabonomics study is a valuable approach in exploring the effect mechanism of nutritional intervention on NTD prevention., (Copyright © 2010 John Wiley & Sons, Ltd.)

Background: Many studies from the Western world have indicated that maternal obesity is associated with an increased risk of neural tube defects (NTDs). However, few reports have been available on this association from Asian populations. Our aim was to examine the relationship between maternal prepregnancy body mass index (BMI) and the risk of NTDs in a population of northern China., Methods: Data were derived from an ongoing population-based case-control study of birth defects in Shanxi province, China. Subjects were 511 NTD cases and 687 controls selected from the same population between January 2003 and June 2007. BMI was based on maternal height and prepregnancy weight as reported within 1 week of delivery., Results: We found no significantly increased risk of NTDs for obese women (adjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.29-1.49) or for underweight women (adjusted OR, 1.00; 95% CI, 0.62-1.62) relative to normal-weight women. We found a significantly reduced risk of overall NTDs (adjusted OR, 0.56; 95% CI, 0.41-0.76) and anencephaly (adjusted OR, 0.40; 95% CI, 0.26-0.62) for overweight women compared to normal-weight women., Conclusions: Our results do not support the association between maternal prepregnancy obesity and increased risk of overall NTDs or of any subtype of NTDs in the Chinese population., (2010 Wiley-Liss, Inc.)

Background: Maternal nutritional factors seem to contribute substantially to the complex etiologies of NTDs. Foremost among these factors is the periconceptional use of supplementation containing folic acid, which is associated with a reduction in the risk of women having NTD-affected pregnancies. This study was designed to observe the effectiveness of multivitamin supplementation containing folic acid in preventing NTDs in a Chinese population and to detect factors that would impact the effectiveness., Methods: Through family planning networks, a population-based community intervention study was carried out in 18 counties of China. Participants were divided into an intervention (taking multivitamin) group and a control group, and were followed up according to periconceptional multivitamin supplementation (in general 6 mg) for 2 years. Women who had a pregnancy were followed up from 28 weeks gestation at least to pregnancy termination, and the outcome was recorded. The incidence rate of the two groups and the relative risks were calculated to evaluate the efficacy of the multivitamin supplement in preventing NTDs., Results: During 2000 and 2002, all of the women having pregnancies with birth defects and women whose pregnancies were without any birth defects were interviewed. Nine NTDs were recorded from 25,444 pregnancies (NTD birth prevalence = 0.35/1,000 pregnancies) in the intervention group and 48 NTDs among 26,599 pregnancies (NTD birth prevalence = 1.80/1,000 pregnancies) in the control group. The protective rate was 80.4%., Conclusions: Periconceptional multivitamin supplementation containing folic acid can prevent the occurrence of NTDs with the beneficial effect dependent on the frequency and timing of the supplementation. Our study suggests that multivitamin supplement containing folic acid taken from a time point of 2 months before conception and continuing until completion of the second month after conception and taken more than five times per week can significantly reduce the risks of NTDs., (Copyright 2008 Wiley-Liss, Inc.)

Salvianolic acid A (SAA), a major effective constituent of Salvia miltiorrhizas, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated for SAA in rat plasma, which was further applied to assess the pharmacokinetics of SAA in rats receiving a single oral dose of SAA. The method used liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode with chloramphenicol as the internal standard. A simple liquid-liquid extraction based on ethyl acetate was employed. The combination of a simple sample cleanup and short chromatographic run time (3 min) increased the throughput of the method substantially. The method was validated over the range 1.4-1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1.4 ng/mL for SAA in plasma. Intra- and inter-day accuracies for SAA were 95-113 and 98-107%, and the inter-day precision was less than 12%. This method is more sensitive and faster than previous methods. After a single oral dose of 100 mg/kg of SAA, the mean peak plasma concentration (Cmax) of SAA was 318 ng/mL at 0.5 h, the area under the plasma concentration-time curve (AUC0-12 h) was 698 +/- 129 ng.h/mL, and the elimination half-life (T1/2) was 3.29 h.

Background: Maternal exposure to flu or fever has been associated with increased risk for neural tube defects (NTDs); however, few studies have considered the effects of medications on the effects of flu or fever. We evaluated the effect of maternal flu or fever, medication use (antibiotics, antipyretics), and their joint effect on NTDs., Methods: Data came from an ongoing population-based case-control study of infants with external malformations in northern China. The case group included 363 infants with NTDs identified between January 2003 and June 2005. Controls were 523 newborn infants without identified congenital anomalies matched by county, sex, maternal ethnic group, and the closest date of conception for infants with any major external malformation. Data were collected by a trained health worker through face-to-face interviews after delivery., Results: NTD risks were significantly associated with maternal flu or fever (adjusted odds ratio [AOR] = 3.93, 95% CI: 2.48-6.23) and antipyretic use (AOR = 4.86, 95% CI: 1.33-17.78), but not with antibiotic use (AOR = 1.75, 95% CI: 0.91-3.38) after adjusting for potential confounders. NTD risk associated with maternal antipyretic use was markedly higher for anencephaly (AOR = 7.03, 95% CI: 1.70-29.04) than for spina bifida (AOR = 3.98, 95% CI: 0.95-16.74). Mothers with flu or fever who were also using antipyretics showed a markedly higher AOR for anencephaly (14.75 vs. 4.52), spina bifida (16.30 vs. 3.85), and all NTDs combined (13.91 vs. 4.04) than mothers with flu or fever who were not using antipyretics. Maternal antibiotics did not markedly change the effects of flu or fever on anencephaly (4.17 vs. 4.83), spina bifida (5.08 vs. 4.21), and all NTDs combined (5.05 vs. 4.29)., Conclusions: Maternal flu or fever and antipyretic use during the periconceptional period increases the risk for NTDs. Maternal exposure to antipyretics together with flu or fever results in a markedly higher risk of NTDs than exposure to flu or fever alone.

Background: There is a considerable body of data demonstrating that periconceptional supplementation of folic acid can prevent a significant proportion of neural tube defects (NTDs). At present, the mechanism by which folic acid exerts its beneficial effect remains unknown. Folate transporter genes, including the reduced folate carrier gene (RFC1), have been proposed as NTD risk factors., Methods: The study population included 104 nuclear families with NTDs and 100 nonmalformed control families. We investigated the possible association between a common RFC1 polymorphism (A80G) and NTD risk among offspring, as well as potential gene-environment interactions between the infant RFC1 genotype and maternal periconceptional use of folic acid through a population-based case-control study., Results: We observed that the infants of the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to the AA genotype (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.04-6.36) in our study population. Among mothers who did not utilize folic acid supplements, the risk for having a child with an NTD was 3.30 (95% CI, 1.15-9.65) for offspring with the GG genotype, compared to the reference (AA) genotype. Children who had the GG genotype and whose mothers did not take folic acid had an elevated risk for NTDs (OR, 8.80; 95% CI, 2.83-28.69), compared to offspring with the AA and GA genotypes whose mothers utilized folic acid supplements., Conclusions: Our findings suggest that the RFC1 G allele is likely to be an important genetic factor in determining folate transport and subsequently may be a risk factor for NTDs in this Chinese population., ((c) 2005 Wiley-Liss, Inc.)

Because of differences in the types and quantities of glycosaminoglycans (GAGs) in various mucopolysaccharidoses (MPSs), MPS screening tests, including the Berry spot and acid turbidity tests, are not specific or sensitive enough for the preliminary diagnosis of MPS. A false-negative result is common. We analyzed urine samples collected from 492 patients who were examined for inborn errors of metabolism using the Berry spot and acid turbidity (qualitative and quantitative) tests. Of those, 48 MPS patients (seven with MPS I, 17 with MPS II, nine with MPS III, 11 with MPS IV, and four with MPS VI) underwent preliminary differentiation between MPS types by two-dimensional electrophoresis (2D-EP), and were confirmed by enzymatic assay. Approximately 21.0% and 7.1% of the 492 samples showed positive reactions in the Berry spot and acid turbidity tests, respectively. Of these, a total of 35 samples with MPS types I, II, and VI showed strong positive reactions in both tests. Five patients with Sanfilippo (MPS III) and six patients with Morquio (IV) syndromes showed false-negative results in both tests. In our study, approximately 13.8% (68 in 492 samples) samples showed a positive reaction in the Berry spot test but a negative one in the acid turbidity test, for unknown reasons. The Berry spot and acid turbidity tests are used extensively for the preliminary diagnosis of MPS in Asia; however, the possibility of a misdiagnosis of MPS type III and IV with both tests should be kept in mind. For accurate diagnosis and confirmation of MPS, the 2D-EP method and enzymatic assay are recommended. They provide high sensitivity, specificity, and efficiency in diagnosing MPS., (Copyright 2002 Wiley-Liss, Inc.)