Trends in the rates of resistance of Ureaplasma urealyticum to antibiotics and identification of the mutation site in the quinolone resistance-determining region in Chinese patients

The resistance of Ureaplasma urealyticum to antibacterials, isolated from 804 patients from the outpatient clinic of the Sir Run Run Shaw Hospital Hangzhou, China, from March to June over six consecutive years (1999-2004) was reviewed. The quinolone resistance-determining region of six strains of U. urealyticum was analyzed. The level of resistance to doxycycline, josamycin, tetracycline, azithromycin, clarithromycin and pristinamycin was below 20% and did not change during the study period. The rate of resistance to fluoroquinolones (ofloxacin, ciprofloxacin) was much greater than these (>50%) and has increased since 1999. The rate of resistance to Erythromycin decreased from 63.9% in 1999 to about 20% from 2000 onwards. The widespread use of fluoroquinolones had led to high resistance rates in U. urealyticum and the emergence of quinolone resistance. Analysis of the gene sequence of topoisomerase IV and DNA gyrase suggested a role for the topoisomerase IV ParE subunit in fluoroquinolone-resistant U. urealyticum.     

The early events of alpha-synuclein oligomerization revealed by photo-induced cross-linking

Assembly of alpha-synuclein (alpha-Syn) into neurotoxic oligomers and fibrils is an important pathogenic feature of Parkinson's disease. Studying the early events of alpha-Syn aggregation, such as oligomerization and nucleation, is indispensable to understanding the complicated process. Here, photo-induced cross-linking of unmodified proteins (PICUP) technique is applied to elucidate the early-stage oligomerization of alpha-Syn. Results show that alpha-Syn in solution exhibits a mixture of various species, including at least monomers, dimers and trimers. Aggregation of alpha-Syn probably originates from the dimeric and trimeric seeds. Furthermore, the N-terminal amphipathic region is proposed to be required for the oligomerization (dimerization and trimerization) process. This observation may extend our knowledge on the early events of alpha-Syn aggregation and the neurotoxic aggregation species.     

Ghrelin reduces injury of hippocampal neurons in a rat model of cerebral ischemia/reperfusion

Ghrelin, an acyl-peptide gastric hormone and an endogenous ligand for growth hormone secretagogue (GHS) receptor 1a (GHS-R 1a) exerts multiple functions. It has been reported that synthetic GHS-hexarelin reduces injury of cerebral cortex and hippocampus after brain hypoxia-ischemia in neonatal rats. However, the effect of ghrelin in tolerance of the brain tissues to cerebral ischemia/reperfusion (I/R) injury has not been studied. The aim of the present study was to examine whether ghrelin have potential protective effect on hippocampal neurons of rats against I/R injury. I/R injury was induced by a modified four-vessel occlusion model. Ghrelin was administered intraperitoneally after the insult. Histological damage of the neurons was determined with hematoxylin-eosin (H&E) staining and assay of the neuronal apoptosis was performed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). The results showed that I/R decreased the number of surviving neurons and induced apoptosis of the neurons in CA1 area of the hippocampus in rats. In contrast, administration of ghrelin significantly increased the number of surviving neurons and reduced the number of TUNEL-positive apoptotic neurons in the equivalent areas after I/R. In conclusion, the present data provide evidence for the first time that ghrelin can exert a neuroprotective role in vivo in the tolerance of hippocampal neurons to I/R injury, and that the mechanism underlying this effect involves an anti-apoptotic property of ghrelin.     

Increased glycolysis in skeletal muscle coordinates with adipose tissue in systemic metabolic homeostasis

Insulin-independent glucose metabolism, including anaerobic glycolysis that is promoted in resistance training, plays critical roles in glucose disposal and systemic metabolic regulation. However, the underlying mechanisms are not completely understood. In this study, through genetically manipulating the glycolytic process by overexpressing human glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3) in mouse skeletal muscle, we examined the impact of enhanced glycolysis in metabolic homeostasis. Enhanced glycolysis in skeletal muscle promoted accelerated glucose disposal, a lean phenotype and a high metabolic rate in mice despite attenuated lipid metabolism in muscle, even under High-Fat diet (HFD). Further study revealed that the glucose metabolite sensor carbohydrate-response element-binding protein (ChREBP) was activated in the highly glycolytic muscle and stimulated the elevation of plasma fibroblast growth factor 21 (FGF21), possibly mediating enhanced lipid oxidation in adipose tissue and contributing to a systemic effect. PFKFB3 was critically involved in promoting the glucose-sensing mechanism in myocytes. Thus, a high level of glycolysis in skeletal muscle may be intrinsically coupled to distal lipid metabolism through intracellular glucose sensing. This study provides novel insights for the benefit of resistance training and for manipulating insulin-independent glucose metabolism.     

Metabolic profiling and phylogenetic analysis of medicinal Zingiber species: Tools for authentication of ginger (Zingiber officinale Rosc)

Phylogenetic analysis and metabolic profiling were used to investigate the diversity of plant material within the ginger species and between ginger and closely related species in the genus Zingiber (Zingiberaceae). In addition, anti-inflammatory data were obtained for the investigated species. Phylogenetic analysis demonstrated that all Zingiber officinale samples from different geographical origins were genetically indistinguishable. In contrast, other Zingiber species were significantly divergent, allowing all species to be clearly distinguished using this analysis. In the metabolic profiling analysis, the Z. officinale samples derived from different origins showed no qualitative differences in major volatile compounds, although they did show some significant quantitative differences in non-volatile composition, particularly regarding the content of [6]-, [8]-, and [10]-gingerols, the most active anti-inflammatory components in this species. The differences in gingerol content were verified by HPLC. The metabolic profiles of other Zingiber species were very different, both qualitatively and quantitatively, when compared to Z. officinale and to each other. Comparative DNA sequence/chemotaxonomic phylogenetic trees showed that the chemical characters of the investigated species were able to generate essentially the same phylogenetic relationships as the DNA sequences. This supports the contention that chemical characters can be used effectively to identify relationships between plant species. Anti-inflammatory in vitro assays to evaluate the ability of all extracts from the Zingiber species examined to inhibit LPS-induced PGE(2) and TNF-alpha production suggested that bioactivity may not be easily predicted by either phylogenetic analysis or gross metabolic profiling. Therefore, identification and quantification of the actual bioactive compounds are required to guarantee the bioactivity of a particular Zingiber sample even after performing authentication by molecular and/or chemical markers.