Macrophage migration inhibitory factor facilitates astrocytic production of the CCL2 chemokine following spinal cord injury

Spinal cord injury causes accumulation of a large number of leukocytes at the lesion site where they contribute to excessive inflammation.Overproduced chemokines are responsible for the migratory process of the leukocytes,but the regulatory mechanism underlying the production of chemokines from resident cells of the spinal cord has not been fully elucidated.We examined the protein levels of macrophage migration inhibitory factor and chemokine C-C motif chemokine ligand 2 in a spinal cord contusion model at different time points following spinal cord injury.The elevation of macrophage migration inhibitory factor at the lesion site coincided with the increase of chemokine C-C motif chemokine ligand 2 abundance in astrocytes.Stimulation of primary cultured astrocytes with different concentrations of macrophage migration inhibitory factor recombinant protein induced chemokine C-C motif chemokine ligand 2 production from the cells,and the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine attenuated the stimulatory effect.Further investigation into the underlying mechanism on macrophage migration inhibitory factor-mediated astrocytic production of chemokine C-C motif chemokine ligand 2 revealed that macrophage migration inhibitory factor activated intracellular JNK signaling through binding with CD74 receptor.Administration of the macrophage migration inhibitory factor inhibitor 4-iodo-6-phenylpyrimidine following spinal cord injury resulted in the reduction of chemokine C-C motif chemokine ligand 2-recruited microglia/macrophages at the lesion site and remarkably improved the hindlimb locomotor function of rats.Our results have provided insights into the functions of astrocyte-activated chemokines in the recruitment of leukocytes and may be beneficial to develop interventions targeting chemokine C-C motif chemokine ligand 2 for neuroinflammation after spinal cord injury.

Standard triple therapy for Helicobacter pylori infection in China: A meta-analysis

AIM:To assess the efficacy and safety of standard triple therapy compared with other pre-existing and new therapies in China.METHODS:Literature searches were conducted in the following databases:PubMed,EMBASE,the Cochrane Central Register of Controlled Trials,the VIP database,the China National Knowledge Infrastructure database,and the Chinese Biomedical Database.A meta-analysis of all randomized controlled trials(RCTs)comparing standard triple therapy for the eradication of Helicobacter pylori with pre-existing and new therapies in China was performed using Comprehensive Meta-Analysis 2.0.There were 49 studies that met our criteria and the qualities of these studies were assessed using the Jadad scale.The Mantel-Haenszel method was used for pooling dichotomous data.We also conducted subgroupanalyses according to age,duration of treatment and drug type.Sensitivity analyses and a cumulative metaanalysis were also performed with CMA 2.0.Publication bias was evaluated using Egger’s test,Begg’s test or a funnel plot.RESULTS:A total of 49 RCTs including 8332 patients were assessed.This meta-analysis showed that standard triple therapy with proton pump inhibitors(PPIs),amoxicillin(AMO)and clarithromycin(CLA)was inferior to sequential therapy[relative risk(RR)=0.863;95%confidence interval(CI):0.824-0.904],but was not superior to quadruple therapy(RR=1.073;95%CI:0.849-1.357)or other triple therapies(RR=1.01;95%CI:0.936-1.089).The meta-analysis also suggested that standard triple therapy is slightly more effective than dual therapy(RR=1.14;95%CI:0.99-1.31).However,the differences were not statistically significant.We removed the only trial with a regimen lasting14 d by sensitivity analysis and found that 7-d standard triple therapy was superior to 7-d dual therapy(RR=1.222;95%CI:1.021-1.461).Moreover,a sub-analysis based on the duration of quadruple therapy indicated that the 7-d and 10-d standard triple therapies were inferior to sequential therapy(RR=0.790;95%CI:0.718-0.868;RR=0.917;95%CI:0.839-1.002,respectively).Additionally,there were no significant differences in cure rate or adverse events among standard triple therapy,quadruple therapy,and other triple therapies(RR=0.940;95%CI:0.825-1.072;RR=1.081;95%CI:0.848-1.378,respectively).Standard triple therapy had a higher occurrence of side effects than sequential therapy(RR=1.283;95%CI:1.066-1.544).CONCLUSION:The eradication rates with a standard triple therapy consisting of PPI,AMO,and CLA are suboptimal in China,and new treatment agents need to be developed.

Fourth-generation quinolones in the treatment of Helicobacter pylori infection: a meta-analysis

AIM To assess the efficacy and safety of fourth-generation quinolones for helicobacter pylori(h. pylori) eradication, we conducted this systematic review and metaanalysis of randomized clinical trials. METHODS Major literature databases(Pub Med, EMBASE and the Cochrane Central Register of Controlled Trials) were searched for relevant articles published prior to February 2018. We performed a meta-analysis of all randomized clinical trials that examined the efficacy of h. pylori eradication therapies and included fourthgeneration quinolones in the experimental arm. Subgroup analyses by regions and different types of fourth-generation quinolones were also performed.RESULTS Ten studies including a total of 2198 patients were assessed. A meta-analysis of randomized controlled trials showed that the eradication rate of therapies containing non-fourth-generation quinolones was significantly lower than that of therapies containing fourth-generation quinolones by intention-to-treat(ITT) analysis [75.4% vs 81.8%; odds ratio(OR) = 0.661; 95% confidence interval(CI): 0.447-0.977; P = 0.038]. This analysis also showed that the eradication rate of the therapies containing non-fourth-generation quinolones was inferior to that of therapies containing fourth-generation quinolones by perprotocol analysis(79.1% vs 84.7%; OR = 0.663; 95%CI: 0.433-1.016; P = 0.059). Moreover, the occurrence of side effects was significantly different between the control and experimental groups by ITT analysis(30.6% vs 19.5%; OR = 1.874; 95%CI: 1.120-3.137; P = 0.017). The sub-analyses also showed significant differences in moxifloxacin therapies vs other fourth-generation quinolone therapies(84.3% vs 71.9%) and in Asian vs European groups(76.7% vs 89.1%).CONCLUSION Therapies containing fourth-generation quinolones achieved a poor eradication rate in the treatment of h. pylori infection. Such regimens might be useful as a rescue treatment based on antimicrobial susceptibility testing. Different antibiotics should be chosen in different regions.

Saponin Accumulation in Flower Buds of Panax notoginseng

Objective Panax notoginseng is an important Chinese medicinal plant. Saponin accumulation is higher in the flower buds than in the other parts of P. notoginseng. However, the flower bud compositions have not yet been quantified. The aim of this study is to investigate the formation and accumulation of saponins in the flower buds of P. notoginseng from different populations and at different growth years. Methods Fourteen types of P. notoginseng with different growing durations and from different areas of Wenshan County, Yunnan Province were collected. We separated P. notoginseng individually into the flower buds, stems, leaves, and roots at the places where it has the highest saponin content. An efficient high-performance liquid chromatography(HPLC) method was developed for simultaneously quantifying two active saponins, ginsenoside Rb1 and ginsenoside Rb3, in the flower buds of P. notoginseng. The total saponin content was determined by using a quantitative vanillin-sulfuric acid colorimetric method. HPLC method was used to establish the fingerprints of 13 saponins and then quantify the composition in the whole plant of P. notoginseng. Results The saponin contents of different parts differ significantly, and the total saponin content and those of Rb1 and Rb3 do not entirely correlated. The flower buds of P. notoginseng contain 27.79% of total saponins, which is the highest saponin content in the whole plant. Fingerprint result showed that different saponins were appeared in different parts of the plant, i.e. flower buds, stems, leaves, and roots.Conclusion The saponin contents from the flower buds of P. notoginseng vary depending on the growth area and duration. The fingerprints show that the saponin contents and compositions vary depending on the part of P. notoginseng. These results are useful for the pharmacological evaluation and quality control of P. notoginseng.

Protection role of resveratrol against alcohol-induced heart defect in zebrafish embryos

To the Editor:Alcohol-induced heart defect is one of the most important clinical manifestations of fetal alcohol spectrum disorder(FASD),characterized by atrioventricular septal defect and arterial conical deformity.[1]Resveratrol,a polyphenol component of the traditional Chinese herb Polygonum cuspidatum,which is mainly extracted from its rhizome,is known to exhibit beneficial effects on the cardiovascular system.For example,resveratrol has beneficial effects on heart dysfunction,myocardial hypertrophy,and pressure overload.Moreover,resveratrol was found to inhibit platelet aggregation,prevent atherosclerosis,and scavenge free radicals.[2]However,the effect of resveratrol on alcohol-induced heart defect during heart formation is still unknown.The unique characteristics of zebrafish embryos,such as their transparent body,in vitro fertilization,and short reproductive cycle,make them an attractive tool for cardiovascular research.Moreover,the immersion-based alcohol delivery method used with zebrafish embryos is non-invasive unlike most of the alcohol administration protocols applied in rodent models.

Comparison on Traditional and Machinery Decoctions for Da-cheng-qi Decoction Based on Chemical Ingredients, Pharmacological Functions, and Clinical Trials

Objective Patients and doctors often have questions about the equivalence of traditional and machinery decoctions. In this article, using Da-cheng-qi Decoction(DCQD) as a model of formula, traditional decoction(TD), machinery decoction under high pressure(MDHP), and machinery decoction under normal pressure(MDNP) were compared. Methods For chemical components, HPLC fingerprints were established and evaluated using AHP combined with CRITIC weighing method; For animals' effects, the experiments of small intestinal propulsion were conducted; For clinical effects, a randomized clinical trial(RCT) was designed and performed. Results Although there were some differences between TD and MDNP in chemical ingredients, there was no significant difference in animal experiments and clinical trials(P > 0.05). Conclusion The traditional and machinery decoctions of DCQD could be used bioequivalently.