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author:("Li, chunked")
1.  Relationship of anabolic and catabolic biomarkers with muscle strength and physical performance in older adults: a population-based cross-sectional study 
Previous studies have found inflammation, growth factors, and androgen signaling pathways all contribute to sarcopenia. However, few studies simultaneously have investigated the association between these potential risk factors and sarcopenia among older people. The aim of the study was to investigate whether elevated levels of inflammatory cytokines combined with low levels of anabolic hormone have a synergy effect on muscle strength and functional decline in older people.
We designed a cross-sectional study of 1,131 subjects aged 60 years and older. Concentrations of serum C-reactive protein, insulin-like growth factor 1 and dehydroepiandrosteronesulphate were assessed using chemiluminescent immunoassays. Handgrip strength was measured using a dynamometer, and physical performance was assessed using a four-meter gait speed and Timed Up and Go test. We defined poor physical performance as a 4-m gait speed <0.8 m/s or Timed Up and Go test ≥13.5 s.
After adjustment for potential confounding factors, in multiple linear regression analysis, C-reactive protein levels are inversely related to handgrip strength (P <0.01), and in multiple logistic regression analysis, C-reactive protein levels are inversely related to poor physical performance (P for trend <0.05) in males, but not in females. After combining three biomarkers, no significant results were observed between biomarker scores and muscle strength or physical performance.
In older males, higher serum C-reactive protein levels, but not insulin-like growth factor 1 and dehydroepiandrosteronesulphate levels, are independently related to lower muscle strength and poor physical performance. In this study we did not observe that a combination of higher catabolic biomarkers and lower anabolic biomarkers were better predictors for muscle strength and physical performance.
PMCID: PMC4545782  PMID: 26286594
2.  Serum Immunoglobulin M Concentration Varies with Triglyceride Levels in an Adult Population: Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIHealth) Cohort Study 
PLoS ONE  2015;10(4):e0124255.
Persistent low-grade inflammation is thought to underlie the pathogenesis of many chronic diseases, such as cardiovascular diseases and metabolic syndrome. Autoimmunity is correlated with increased levels of chronic low-grade inflammation, and immunoglobulin M (IgM) is reactive to autoantigens and believed to be important for autoimmunity. Triglyceride (TG) is fatty acid carrier and initiator of oxidative stress, and it has been hypothesized that TG stimulates B cells to secrete IgM. However, few studies have investigated the relationship between TG and IgM in human populations. We designed a cross-sectional and prospective cohort study to evaluate how serum TG levels are related to IgM concentration. Participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. Both a baseline cross-sectional (n = 10,808) and a prospective assessment (n = 2,615) were performed. Analysis of covariance was used in the cross-sectional analysis. After multiple adjustments for confounding factors, serum IgM level in the highest quartile of TG in males was significantly higher than levels in lower quartiles (P <0.05). There was no significant difference between the four quartiles in females (P = 0.91). In follow-up analysis, a multiple linear regression model showed a significant and positive correlation between changes in IgM levels and changes of TG concentration in males (P = 0.04, standard β coefficient = 0.882). This cross-sectional and cohort study is the first to show that serum concentration of IgM varies with TG levels in adult male populations. Further research is needed to explore the mechanism by which TG leads to increased IgM concentration.
PMCID: PMC4411052  PMID: 25915947
3.  Association between Complement C3 and Prevalence of Fatty Liver Disease in an Adult Population: A Cross-Sectional Study from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIHealth) Cohort Study 
PLoS ONE  2015;10(4):e0122026.
Activation of the innate immune system plays a key role in the development of fatty liver disease (FLD). The complement system is a major humoral component of the innate immune response and complement C3 plays a central role, implying that C3 may be a powerful predictor or therapeutic target for FLD. However, few studies have assessed the association between C3 and FLD in a large population. Here we use a cross-sectional study to investigate the link between serum C3 levels and FLD. Participants were recruited from Tianjin Medical University’s General Hospital-Health Management Centre. Serum C3 was measured using immunoturbidimetry method and FLD was diagnosed by liver ultrasonography. Multiple logistic regression analysis was used to examine the association between quartiles of C3 and FLD prevalence. The overall prevalence of nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) were 37.3% and 10.1%, respectively. After adjusting for covariates, the odds ratio of having NAFLD or AFLD (only in males) in the fourth quartile of C3 compared with the first quartile was 4.13 times greater (95% confidence interval, 2.97-5.77) (trend P values < 0.0001) and 2.09 times greater (95% confidence interval, 1.08-4.18) (trend P values = 0.02). This is the first study to demonstrate that serum C3 levels are independently associated with a higher prevalence of NAFLD and AFLD (only in males) in an adult population. Further studies are needed to establish a causal link and determine the precise role of C3 in FLD.
PMCID: PMC4391843  PMID: 25856141
4.  Role of salivary anti-SSA/B antibodies for diagnosing primary Sjögren’s syndrome 
The diagnosis of primary Sjögren’s syndrome (pSS) is complex, and the saliva test is a potential method to improve the existing diagnostic criteria. Objective: To estimate the diagnostic accuracy of salivary anti-SSA/B antibodies in primary Sjögren’s syndrome (pSS), and to analyze their correlations with clinical and laboratory profiles. Study Design: This study enrolled 100 pSS patients and 140 non-pSS controls, including 40 rheumatoid arthritis (RA) patients, 40 systemic lupus erythematosus (SLE) patients, and 60 healthy controls. Unstimulated whole saliva and stimulated parotid saliva samples were collected from the subjects. Salivary anti-SSA/B antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory data were retrieved from the medical records. Results: In the pSS group, the sensitivity of anti-SSA and anti-SSB antibodies in whole saliva was 49% and 29%, respectively, and the specificity was 87.5% and 95%. The sensitivity of anti-SSA and anti-SSB antibodies in parotid saliva was 32% and 8%, respectively, and the specificity was 95.52% and 97.86%, respectively. In the pSS group, the diagnostic accuracy of anti-SSA/B antibodies in whole saliva was significantly higher than in parotid saliva (p<0.05), but was significantly lower than in serum (p<0.05). The salivary flow rate in the pSS group positive for whole salivary anti-SSA was significantly lower than in the negative group (p<0.05). The prevalence of rheumatoid factor and antinuclear factor were significantly higher in salivary SSB-positive pSS patients than in SSB-negative patients (p<0.05). Conclusions: Compared to parotid saliva, whole saliva is a more suitable diagnostic fluid. Using salivary anti-SSA/B antibodies as a single test item is insufficient given the relatively low sensitivity. Further studies should investigate the possibility of combining tests for different salivary autoantibodies as a method for diagnosing pSS.
Key words:Primary Sjögren’s syndrome, salivary diagnostics, anti-SSA autoantibodies, anti-SSB autoantibodies.
PMCID: PMC4393977  PMID: 25475778
5.  PKC Activation in Niemann Pick C1 Cells Restores Subcellular Cholesterol Transport 
PLoS ONE  2013;8(8):e74169.
Activation of protein kinase C (PKC) has previously been shown to ameliorate the cholesterol transport defect in Niemann Pick Type C1 (NPC1) cells, presumably by increasing the soluble levels of one of its substrates, vimentin. This activity would then restore the vimentin cycle in these cells and allow vimentin-dependent retrograde transport to proceed. Here, we further investigate the effects of PKC activation in NPC1 cells by evaluating different isoforms for their ability to solubilize vimentin and correct the NPC1 cholesterol storage phenotype. We also examine the effects of PKC activators, including free fatty acids and the PKC-specific activator diazoxide, on the NPC1 disease phenotype. Our results indicate that PKC isoforms α, βII, and ε have the greatest effects on vimentin solubilization. Furthermore, expression or activation of PKCε in NPC1 cells dramatically reduces the amount of stored cholesterol and restores cholesterol transport out of endocytic vesicles. These results provide further support for the contribution of PKCs in NPC1 disease pathogenesis and suggest that PKCs may be targeted in future efforts to develop therapeutics for NPC1 disease.
PMCID: PMC3744505  PMID: 23977398
6.  The mechanisms of microtubule catastrophe and rescue: implications from analysis of a dimer-scale computational model 
Molecular Biology of the Cell  2012;23(4):642-656.
ETOC: The behavior of a dimer-scale computational model predicts that short interprotofilament “cracks” (laterally unbonded regions between protofilaments) exist even at the tips of growing MTs and that rapid fluctuations in the depths of these cracks govern both catastrophe and rescue.
Microtubule (MT) dynamic instability is fundamental to many cell functions, but its mechanism remains poorly understood, in part because it is difficult to gain information about the dimer-scale events at the MT tip. To address this issue, we used a dimer-scale computational model of MT assembly that is consistent with tubulin structure and biochemistry, displays dynamic instability, and covers experimentally relevant spans of time. It allows us to correlate macroscopic behaviors (dynamic instability parameters) with microscopic structures (tip conformations) and examine protofilament structure as the tip spontaneously progresses through both catastrophe and rescue. The model's behavior suggests that several commonly held assumptions about MT dynamics should be reconsidered. Moreover, it predicts that short, interprotofilament “cracks” (laterally unbonded regions between protofilaments) exist even at the tips of growing MTs and that rapid fluctuations in the depths of these cracks influence both catastrophe and rescue. We conclude that experimentally observed microtubule behavior can best be explained by a “stochastic cap” model in which tubulin subunits hydrolyze GTP according to a first-order reaction after they are incorporated into the lattice; catastrophe and rescue result from stochastic fluctuations in the size, shape, and extent of lateral bonding of the cap.
PMCID: PMC3279392  PMID: 22190741
7.  Cyclodextrin Induces Calcium-Dependent Lysosomal Exocytosis 
PLoS ONE  2010;5(11):e15054.
Cyclodextrins (CDs) have long been used to manipulate cellular cholesterol levels both in vitro and in vivo, but their direct effects at a cellular level are not well characterized. Recently, CDs have garnered much interest because of their ability to clear stored cholesterol from Niemann Pick Type C (NPC) cells and markedly prolong the life of NPC1 disease mice. Here, we investigate the hypothesis that treatment with 2-hydroxypropyl- β-cyclodextrin (HPB-CD) stimulates lysosomal exocytosis in a calcium-enhanced manner. We propose that this exocytosis is the mechanism by which HPB-CD ameliorates the endolysosomal cholesterol storage phenotype in NPC cells. These findings have significant implications for the use of HPB-CD in biochemical assays and data interpretation as well as for their use for the treatment for NPC and other disorders.
PMCID: PMC2993955  PMID: 21124786
8.  Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis 
Arthritis Research & Therapy  2010;12(6):R210.
Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. Here, potential immunosuppressive effects of human UC-MSCs in RA were evaluated.
The effects of UC-MSCs on the responses of fibroblast-like synoviocytes (FLSs) and T cells in RA patients were explored. The possible molecular mechanism mediating this immunosuppressive effect of UC-MSCs was explored by addition of inhibitors to indoleamine 2,3-dioxygenase (IDO), Nitric oxide (NO), prostaglandin E2 (PGE2), transforming growth factor β1 (TGF-β1) and interleukin 10 (IL-10). The therapeutic effects of systemic infusion of human UC-MSCs on collagen-induced arthritis (CIA) in a mouse model were explored.
In vitro, UC-MSCs were capable of inhibiting proliferation of FLSs from RA patients, via IL-10, IDO and TGF-β1. Furthermore, the invasive behavior and IL-6 secretion of FLSs were also significantly suppressed. On the other hand, UC-MSCs induced hyporesponsiveness of T cells mediated by PGE2, TGF-β1 and NO and UC-MSCs could promote the expansion of CD4+ Foxp3+ regulatory T cells from RA patients. More importantly, systemic infusion of human UC-MSCs reduced the severity of CIA in a mouse model. Consistently, there were reduced levels of proinflammatory cytokines and chemokines (TNF-α, IL-6 and monocyte chemoattractant protein-1) and increased levels of the anti-inflammatory/regulatory cytokine (IL-10) in sera of UC-MSCs treated mice. Moreover, such treatment shifted Th1/Th2 type responses and induced Tregs in CIA.
In conclusion, human UC-MSCs suppressed the various inflammatory effects of FLSs and T cells of RA in vitro, and attenuated the development of CIA in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA. In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the participation of Tregs.
PMCID: PMC3046518  PMID: 21080925

Results 1-8 (8)