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Articles by X Pan
Total Records ( 5 ) for X Pan
  X Pan , N Gong , J Zhao , Z Yu , F Gu , J Chen , X Sun , L Zhao , M Yu , Z Xu , W Dong , Y Qin , G Fei , C Zhong and T. L. Xu

Reduction of glucose metabolism in brain is one of the main features of Alzheimer’s disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer’s disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer’s disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3 and -3β, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. Therefore, in the animal Alzheimer’s disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer’s disease treatment.

  K Nohara , T Suzuki , K Ao , H Murai , Y Miyamoto , K Inouye , X Pan , H Motohashi , Y Fujii Kuriyama , M Yamamoto and C. Tohyama

The ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) has been implicated in various immune functions. Our previous studies have shown that AhR activation by exposure of ovalbumin (OVA)-immunized mice to the potent ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases immunization-induced IFN- production in the spleen and suppresses the production of Th2 cytokines and OVA-specific antibodies. In the present study, we used transgenic (Tg) mice that express a constitutively active mutant of aryl hydrocarbon receptor (CA-AhR) specifically in T-lineage cells to clarify the role of AhR activation in T cells in these reactions. The results of this study clearly demonstrated that AhR activation only in the T cells augments IFN- production upon OVA immunization. By contrast, production of Th2 cytokines and antibodies were not significantly suppressed by CA-AhR in the T cells. These results suggest that suppression of Th2 cytokines and antibodies production require AhR activation not only in T cells but also in other cell types as caused by TCDD exposure. Alternatively, these results may indicate that IFN- augmentation and Th2 cytokines and antibodies suppression depend on different ways of functions of AhR in the T cells and that CA-AhR does not replicate the suppressive effect of TCDD-activated AhR on Th2 cytokines and antibodies. Expression of CA-AhR in the T cells was also shown to increase the percentage of CD25+ cells among CD4+ cells in the thymus and spleen. Thus, studies using T-cell-specific CA-AhR Tg mice provide a way to dissect the role of AhR in individual cell types and how the AhR functions.

  Q Niu , Z Huang , Y Shi , L Wang , X Pan and C. Hu

Objectives. To identify novel serum protein biomarkers and establish diagnostic pattern for rheumatoid arthritis (RA) by using proteomic technology. Methods. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined with weak cationic exchange magnetic beads. A training set of spectra, derived from analyzing sera from 22 patients with RA, 26 patients with other autoimmune diseases and 25 age- and sex-matched healthy volunteers, was used to train and develop a decision tree model with a machine learning algorithm called decision boosting. A blinded testing set, including 21 patients with RA, 24 patients with other autoimmune diseases and 25 healthy people, was used to examine the accuracy of the model. Results. A decision tree model was established, consisting of four potential protein biomarkers whose m/z values were 4966.88, 5065.3, 5636.97 and 7766.87, respectively. In validation test, the decision tree model could differentiate RA from other autoimmune diseases and healthy people with the sensitivity of 85.71% and specificity of 87.76%, respectively. Conclusions. The present data suggested that MALDI-TOF-MS combined with magnetic beads could screen and identify some novel serum protein biomarkers related to RA. The proteomic pattern based on the four candidate biomarkers is of value for laboratory diagnosis of RA.

  H Li , Y Bao , A Xu , X Pan , J Lu , H Wu , H Lu , K Xiang and W. Jia

Objective: Fibroblast growth factor (FGF) 21, a hormone primarily secreted by liver, has recently been shown to have beneficial effects on glucose and lipid metabolism and insulin sensitivity in animal models. This study investigated the association of serum FGF21 levels with insulin secretion and sensitivity, as well as circulating parameters of lipid metabolism and hepatic enzymes in Chinese subjects.

Design: Serum FGF21 levels were determined by ELISA in 134 normal glucose tolerance (NGT), 101 isolated-impaired fasting glucose, and 118 isolated-impaired glucose tolerance (I-IGT) Chinese subjects, and their association with parameters of adiposity, glucose, and lipid profiles, and levels of liver injury markers was studied. In a subgroup of this study, the hyperglycemic clamp technique was performed in 31 NGT, 17 isolated-impaired fasting glucose, and 15 I-IGT subjects to measure insulin secretion and sensitivity to test the associations with serum FGF21.

Results: The serum FGF21 levels in I-IGT were significantly higher than NGT subjects [164.6 pg/ml (89.7, 261.0) vs. 111.8 pg/ml (58.0, 198.9); P < 0.05], and correlated positively with several parameters of adiposity. Multiple stepwise regression analysis showed an independent association of serum FGF21 with serum triglycerides, total cholesterol, and -glutamyltransferase (all P < 0.05). However, FGF21 did not correlate with insulin secretion and sensitivity, as measured by hyperglycemic clamp and a 75-g oral glucose tolerance test.

Conclusions: Serum levels of FGF21 are closely related to adiposity, lipid metabolism, and biomarkers of liver injury but not insulin secretion and sensitivity in humans.

  V. Y Ng , N Arora , T. M Best , X Pan and T. J. Ellis

Background: Recent case studies on the surgical treatment of femoroacetabular impingement (FAI) have introduced a large amount of clinical data. However, there has been no clear consensus on its efficacy.

Hypothesis: The current literature can be clarified to address 4 questions: (1) Does treatment for FAI succeed in improving symptoms? (2) In which subset of patients should treatment for FAI be avoided? (3) Is labral refixation superior to simple resection? (4) Does treatment for FAI alter the natural progression of osteoarthritis in this group of typically young patients?

Study Design: Systematic review.

Methods: Twenty-three reports of case studies on the surgical treatment of FAI were identified and a systematic review was conducted. Data from each study were collected to answer each of the 4 focus questions.

Results: This review of 970 cases included 1 level II evidence trial, 2 level III studies, and 20 level IV studies. Based on patient outcome scores and effect size, all studies demonstrated improvement of patient symptoms. Up to 30% of patients will eventually require total hip arthroplasty; those patients with Outerbridge grade III or IV cartilage damage seen intraoperatively or with preoperative radiographs showing greater than Tonnis grade I osteoarthritis will have worse outcomes with treatment for FAI. Only 2 studies directly compared labral refixation with labral debridement. Several studies reported postoperative osteoarthritis findings; only a minority of these patients had progression of their osteoarthritis.

Conclusion: Surgical treatment for FAI reliably improves patient symptoms in the majority of patients without advanced osteoarthritis or chondral damage. Early evidence supports labral refixation. It is too soon to predict whether progression of osteoarthritis is delayed.

Clinical Relevance: These results may be used to help predict the outcome of surgical treatment of FAI in different patient populations and to assess the need for labral refixation.

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