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1.  Xiaocheng Gu (1930-2012) 
Cell Research  2013;23(2):167.
PMCID: PMC3567824
2.  Investigation on the role of the molecular weight of polyvinyl pyrrolidone in the shape control of high-yield silver nanospheres and nanowires 
Serving as shape control agent, polyvinyl pyrrolidone (PVP) has been widely used in chemical synthesis of metal nanoparticles. However, the role of molecular weight (MW) of PVP has been rarely concerned. In this study, we show a facile method to control the shapes of silver nanocrystals using PVP with different MWs. PVPMW=8,000, PVPMW=29,000, PVPMW=40,000, and PVPMW=1,300,000 are compared in the present study. Surprisingly, high-yield silver rodlike nanostructures, nanospheres, and nanowires can be obtained under the same growth environment and reactant concentrations by simply changing the MW of PVP. The mechanism studies of the role of PVP with different MWs in the growth process were carried out systemically using the morphology and spectroscopic measurement, FT-IR spectrum analysis, and seed crystallization monitoring. The results indicate that the MW of PVP plays a determinant role in the morphology and optical property control of the silver nanocrystals. Meantime, the concentration of PVP was found to be an assistant factor to further improve the shape and the yield of the synthesized nanocrystals.
PMCID: PMC3922195  PMID: 24418460
Polyvinyl pyrrolidone; Molecular weight; Nanowire; Nanosphere
3.  Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in CKD 
Chronic kidney disease (CKD) impairs intestinal barrier function which leads to endotoxemia and systemic inflammation. We have found depletion of intestinal epithelial tight junction (TJ) proteins in animals with CKD. We further showed that addition of ESRD patients' plasma to the culture medium provokes marked drop in transepithelial electrical resistance (TER) and depletion of TJ proteins in cultured human enterocytes. These effects were less severe with post- than pre-hemodialysis plasma suggesting the role of dialyzable agent(s). This study tested the hypothesis that intestinal barrier dysfunction in uremia may be due to diffusion of urea into the gut and its conversion to ammonia by microbial urease.
Human enterocytes (T84 cells) were seeded on Transwell plates and utilized when TER exceeded 1,000 Ω.cm2 to ensure full polarization and TJ formation. Confluent cells were then incubated for 24 hr in media containing zero, 42, or 74 mg/dl urea or urea plus urease to simulate presence of microbial flora.
At clinically-relevant concentrations, urea caused a concentration-dependent fall in TER and the key TJ protein; cluadin-1, occludin, and ZO1. The effects of urea were dramatically amplified by urease causing cells detachment, dissipation of TER, and massive loss of TJ proteins.
uremia-induced disruption of intestinal TJ and barrier function is, in part, mediated by urea which is generally considered to be a nontoxic retained metabolite. These findings reveal a novel mechanism for salutary effect of urea-lowering strategies e.g. low protein diet and longer and more frequent dialysis regimens in advanced CKD.
PMCID: PMC3686571  PMID: 23258127
Endotoxin; Inflammation; Gastrointestinal pathology; End-stage renal disease; uremia; cardiovascular disease
4.  MspI and Ile462Val Polymorphisms in CYP1A1 and Overall Cancer Risk: A Meta-Analysis 
PLoS ONE  2013;8(12):e85166.
Cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family, which is a key enzyme in the metabolism of many endogenous substrates and exogenous carcinogens. To date, many studies have examined the association between CYP1A1 MspI and Ile462Val polymorphisms and cancer risk in various populations, but their results have been conflicting rather than consistent.
To assess this relationship more precisely, a meta-analysis based on 198 publications was performed. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with a chi-square-based Q-test.
Overall, a significant elevated risk of cancer was associated with CYP1A1 MspI and Ile462Val polymorphisms for all genetic models studied. Further stratified analysis by cancer types revealed that the MspI polymorphism may increase the risk of lung cancer and cervical cancer whereas the Ile462Val polymorphism may contribute to a higher risk of lung cancer, leukemia, esophageal carcinoma, and prostate cancer. In the subgroup analysis by ethnicity, obvious associations were found in the Asian population for the MspI polymorphism while an increased risk of cancer was observed in Asians and Caucasians for the Ile462Val polymorphism.
The results of this meta-analysis suggest that CYP1A1 MspI and Ile462Val polymorphisms contribute to increased cancer susceptibility among Asians. Additional comprehensive system analyses are required to validate this association and other related polymorphisms.
PMCID: PMC3877352  PMID: 24391993
5.  Quantitative T2 mapping to characterize the process of intervertebral disc degeneration in a rabbit model 
To investigate the potential of T2 mapping for characterizing the process of intervertebral disc degeneration (IDD) in a rabbit model.
Thirty-five rabbits underwent an annular stab to the L4/5 discs (L5/6 discs served as internal normal controls). Degenerative changes were graded according to the modified Thompson classification and quantified in T2 respectively at pre-operation, 1, 3, 6, 12 and 24 weeks postoperatively. After MRI analysis, expression analysis of aggrecan and type II collagen gene in nucleus pulposus (NP) was performed using real time polymerase chain reaction (real-time PCR). The longitudinal changes in NP T2 and gene expressions were studied by repeated measures and ANOVA, linear regression was performed for their correlations through the process of IDD. The reliability analysis of method of measurement of NP T2 was also performed.
There was a strong inverse correlation between NP T2 and Thompson grades (r = -0.85). The decline of L4/5 NP T2 through 24 weeks was nonlinear, the most significant decrease was observed in 3 weeks postoperatively (P<0.05). The tendency was confirmed at gene expression levels. NP T2 correlated strongly with aggrecan (R2 = 0.85, P<0.01) and type II collagen (R2 = 0.78, P<0.01) gene expressions. The intraclass correlation coefficients for interobserver and intraobserver reliability were 0.963 and 0.977 respectively.
NP T2 correlates well with aggrecan and type II collagen gene expressions. T2 mapping could act as a sensitive, noninvasive tool for quantitatively characterizing the process of IDD in longitudinal study, help better understanding of the pathophysiology of IDD, assist us to detect the degenerative cascade, and develop a T2-based quantification scale for evaluation of IDD and efficacy of therapeutic interventions.
PMCID: PMC3878325  PMID: 24344686
Intervertebral disc; Degeneration; Animal model; MRI; T2 mapping
6.  Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium 
American journal of nephrology  2012;36(5):438-443.
Back ground
CKD causes intestinal barrier dysfunction which by allowing influx of endotoxin and other noxious products contributes to the CKD-associated systemic inflammation and uremic toxicity. We have recently shown that intestinal barrier dysfunction in CKD animals is due to degradation of trans-cellular [claudin-1 and occludin] and intra-cellular [ZO1] constituents of epithelial tight junction (TJ). This study determined whether CKD-associated disruption of TJ is mediated by retained uremic toxins/metabolites and if so whether they are removed by hemodialysis.
The TJ-forming human enterocytes (T84 cells) were seeded on the Transwell plates and utilized when trans-epithelial electrical resistance (TER) exceeded 1000 mΩ/cm2 to ensure full polarization and TJ formation. The cells were then incubated for 24 hr in media containing 10% pre- or post-hemodialysis plasma from ESRD patients or healthy individuals. TER was then measured and cells were processed for Western blot and immunohistological analyses.
Compared with the control plasma, incubation in media containing pre-dialysis plasma from ESRD patients resulted in a marked drop in TER pointing to increased epithelial permeability. This was accompanied by significant reductions in cluadin-1 (85%), occludin (15%), and ZO1 (70%) abundance. The severity of TJ damage and dysfunction was significantly less in cells exposed to the post-dialysis than per-dialysis plasma. These findings point to the presence of as-yet unidentified product(s) in the uremic plasma capable of depleting epithelial TJ.
Exposure to uremic milieu damages the intestinal epithelial TJ and impairs its barrier function, events which are mediated by agents which are partially removed by hemodialysis.
PMCID: PMC3725306  PMID: 23128155
Tight junction; inflammation; hemodialysis; ESRD; CKD
7.  Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation 
Nephrology Dialysis Transplantation  2011;27(7):2686-2693.
Inflammation is a constant feature and a major mediator of the progression of chronic kidney disease (CKD) and its numerous complications. There is increasing evidence pointing to the impairment of intestinal barrier function and its contribution to the prevailing inflammation in advanced CKD. Under normal condition, the intestinal epithelium and its apical tight junction prevent entry of the luminal microorganisms, harmful microbial by-products and other noxious contents in the host's internal milieu. This study was designed to test the hypothesis that impaired intestinal barrier function in uremia must be due to disruption of the intestinal tight junction complex.
Sprague–Dawley (SD) rats were randomized to undergo 5/6 nephrectomy (CKD) or sham-operation (control) and observed for 8 weeks. In a separate experiment, SD rats were rendered uremic by addition of 0.7% adenine to their food for 2 weeks and observed for an additional 2 weeks. Rats consuming a regular diet served as controls. The animals were then euthanized and their colons were removed and processed for expression of the key constituents of the tight junction complex using real-time polymerase chain reaction, western blot analysis and immunohistological examinations.
The CKD groups showed elevated plasma urea and creatinine, reduced creatinine clearance, thickened colonic wall and heavy infiltration of mononuclear leukocytes in the lamina propria. This was associated with marked reductions in protein expressions of claudin-1 (70–90%), occludin (50–70%) and ZO-1 (80–90%) in the colonic mucosa in both CKD models compared with the corresponding controls. The reduction in the abundance of the given proteins was confirmed by immunohistological examinations. In contrast, messenger RNA abundance of occludin, claudin-1 and ZO-1 was either unchanged or elevated pointing to the post-transcriptional/post-translational modification as a cause of the observed depletion of the tight junction proteins.
The study revealed, for the first time, that uremia results in depletion of the key protein constituents of the colonic tight junction, a phenomenon which can account for the impaired intestinal barrier function and contribute to the systemic inflammation in CKD.
PMCID: PMC3616758  PMID: 22131233
claudin; end-stage renal disease; gastrointestinal tract; intestinal barrier defect; occludin
8.  Characterizing Venous Vasculatures of Hepatocellular Carcinoma Using a Multi-Breath-Hold Two-Dimensional Susceptibility Weighted Imaging 
PLoS ONE  2013;8(6):e65895.
The aim of our study is to characterize the venous vasculatures of hepatocellular carcinoma (HCC) using a multi-breath-hold two-dimensional (2D) susceptibility weighted imaging (SWI) in comparison with conventional Magnetic Resonance Imaging (MRI) sequences. Twenty-nine patients with pathologically confirmed HCC underwent MR examination at a 3.0 T scanner. The number of venous vascularity in or around the lesion was counted and the image quality was subjectively evaluated by two experienced radiologists independently based on four image sets: 1) SWI, 2) T1-weighted sequence, 3) T2-weighted sequence, and 4) T1-weighted dynamic contrast-enhanced (DCE) sequence. Of the 29 patients, a total of 33 liver lesions were detected by both SWI and conventional MR sequences. In the evaluation of the conspicuity of venous vascularity, a mean of 10.7 tumor venous vessels per mass was detected by the SWI and 3.9 tumor vasculatures were detected by T1-weighted DCE (P<0.0001), while none was detected by T1-, T2-weighted sequences. The Pearson correlation coefficients between the lesion sizes and the number of tumor vasculatures detected by T1-weighted DCE was 0.708 (P<0.001), and 0.883 by SWI (P<0.001). Our data suggest that SWI appears to be a more sensitive tool compared to T1-weighted DCE sequence to characterize venous vasculature in liver lesions.
PMCID: PMC3683022  PMID: 23799060
9.  A Pro-Inflammatory Role of C5L2 in C5a-Primed Neutrophils for ANCA-Induced Activation 
PLoS ONE  2013;8(6):e66305.
The complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In particular, C5a and its receptor on neutrophils, CD88, play a central role. The functional role of the second receptor of C5a, C5L2, remains unclear. In the current study, we investigated the role of C5L2 in C5a-primed neutrophils for ANCA-induced activation.
The effect of blocking C5L2 by anti-human C5L2 blocking antibody were tested on respiratory burst and degranulation of C5a-primed neutrophils activated with ANCA, as well as on membrane-bound proteinase 3 (mPR3) and concentration of myeloperoxidase (MPO) in supernatant of C5a-primed neutrophils. An antagonist for CD88 was also employed.
Blocking C5L2 resulted in a significantly decreased MPO concentration in the supernatant of C5a-primed neutrophils. mPR3 expression increased from 209.0±43.0 in untreated cells to 444.3±60.8 after C5a treatment (P<0.001), and decreased to 375.8±65.44, 342.2±54.3 and 313.7±43.6 by pre-incubating blocking C5L2 antibody at 2.5 µg/ml, 5 µg/ml or 10 µg/ml (compared with C5a-priming group, P<0.001, P<0.001, and P<0.001), respectively. In C5a-primed neutrophils, subsequently activating with MPO-ANCA-positive IgG, the MFI value was 425.8±160.6, which decreased to 292.8±141.2, 289.7±130.0 and 280.3±136.4 upon pre-incubation with mouse anti-human C5L2 blocking antibody at 2.5 µg/ml, 5 µg/ml or 10 µg/ml (compared with C5a-primed neutrophils, for MPO-ANCA-positive IgG-induced activation, P<0.05, P<0.05, and P<0.05), respectively. Blocking C5L2 also resulted in significantly decreased C5a-primed neutrophils for PR3-ANCA-positive IgG-induced activation. Moreover, the lactoferrin concentration in the supernant significantly decreased in pre-incubation with anti-human C5L2 blocking antibody, compared with C5a-primed neutrophils induced by PR3- or MPO-ANCA-positive IgG.
C5L2 may be implicated in the pro-inflammatory role in C5a-primed neutrophils for ANCA-induced activation.
PMCID: PMC3681967  PMID: 23785491
10.  Intracoronary versus Intravenous Administration of Abciximab in Patients with Acute Coronary Syndrome: A Meta-Analysis 
PLoS ONE  2013;8(2):e58077.
Abciximab is a widely used adjunctive therapy for acute coronary syndrome (ACS). However, the effect of intracoronary (IC) administration of abciximab on cardiovascular events remains unclear when compared with intravenous (IV) therapy.
Methodology and Principal Findings
We systematically searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases and reference lists of articles and proceedings of major meetings for obtaining relevant literature. All eligible trials included ACS patients who received either IC administration of abciximab or IV therapy. The primary outcome was major cardiovascular events, and secondary outcomes included total mortality, reinfarction, and any possible adverse events. Of 660 identified studies, we included 9 trials reporting data on 3916 ACS patients. Overall, IC administration of abciximab resulted in 45% reduction in relative risk for major cardiovascular events (RR; 95% confidence interval [CI], 24−60%), 41% reduction in RR for reinfarction (95% CI, 7−63%), and 44% reduction in RR for congestive heart failure relative to IV therapy (95% CI, 8−66%); however, compared to IV therapy, IC administration of abciximab had no effect on total mortality (RR, 0.69; 95% CI, 0.45−1.07). No other significant differences were identified between the effect of IC abciximab administration and IV therapy.
IC administration of abciximab can reduce the risk of major cardiovascular events, reinfarction, and congestive heart failure when compared with IV therapy.
PMCID: PMC3585408  PMID: 23469144
11.  Room temperature multiferroicity in Bi4.2K0.8Fe2O9+δ 
Scientific Reports  2013;3:1245.
Magnetoelectric multiferroics are materials that have coupled magnetic and electric dipole orders, which can bring novel physical phenomena and offer possibilities for new device functions. In this report, single-crystalline Bi4.2K0.8Fe2O9+δ nanobelts which are isostructural with the high-temperature superconductor Bi2Sr2CaCu2O8+δ are successfully grown by a hydrothermal method. The regular stacking of the rock salt slabs and the BiFeO3-like perovskite blocks along the c axis of the crystal makes the Bi4.2K0.8Fe2O9+δ nanobelts have a natural magnetoelectric–dielectric superlattice structure. The most striking result is that the bulk material made of the Bi4.2K0.8Fe2O9+δ nanobelts is of multiferroicity near room temperature accompanied with a structure anomaly. When an external magnetic field is applied, the electric polarization is greatly suppressed, and correspondingly, a large negative magnetocapacitance coefficient is observed around 270 K possibly due to the magnetoelectric coupling effect. Our result provides contributions to the development of single phase multiferroics.
PMCID: PMC3570784  PMID: 23409236
12.  Antifungal Activity of Bacillus amyloliquefaciens NJN-6 Volatile Compounds against Fusarium oxysporum f. sp. cubense 
Applied and Environmental Microbiology  2012;78(16):5942-5944.
Bacillus amyloliquefaciens NJN-6 produces volatile compounds (VOCs) that inhibit the growth and spore germination of Fusarium oxysporum f. sp. cubense. Among the total of 36 volatile compounds detected, 11 compounds completely inhibited fungal growth. The antifungal activity of these compounds suggested that VOCs can play important roles over short and long distances in the suppression of Fusarium oxysporum.
PMCID: PMC3406121  PMID: 22685147
13.  Effect of salvianolate on intestinal epithelium tight junction protein zonula occludens protein 1 in cirrhotic rats 
AIM: To study the effect of salvianolate on tight junctions (TJs) and zonula occludens protein 1 (ZO-1) in small intestinal mucosa of cirrhotic rats.
METHODS: Cirrhosis was induced using carbon tetrachloride. Rats were randomly divided into the untreated group, low-dose salvianolate (12 mg/kg) treatment group, medium-dose salvianolate (24 mg/kg) treatment group, and high-dose salvianolate (48 mg/kg) treatment group, and were treated for 2 wk. Another 10 healthy rats served as the normal control group. Histological changes in liver tissue samples were observed under a light microscope. We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system. Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy. The changes in ZO-1 expression, a tight junction protein, were analyzed by immunocytochemistry. The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.
RESULTS: In the untreated group, hepatocytes showed a disordered arrangement, fatty degeneration was extensive, swelling was obvious, and disorganized lobules were divided by collagen fibers in hepatic tissue, which were partly improved in the salvianolate treated groups. In the untreated group, abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts, and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment. Compared with the untreated group, no differences in intestinal villi width between the five groups were observed. The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group (P < 0.01). The number of microvilli decreased and showed irregular lengths and arrangements in the untreated group. The intercellular space between epithelial cells was wider. The TJs were discontinuous, which indicated disruption in TJ morphology in the untreated group. In the treated groups, the microvilli in the intestinal epithelium were regular and the TJs were gradually integrated and distinct. The expression of ZO-1 decreased in the small intestine of the untreated cirrhotic rats. The high expression rate of ZO-1 in ileal mucosa in the untreated group was significantly lower than that in the medium-dose salvianolate group (21.43% vs 64.29%, χ2 = 5.25, P < 0.05), high-dose salvianolate group (21.43% vs 76.92%, χ2 = 8.315, P < 0.01) and normal group (21.43% vs 90%, χ2 = 10.98, P < 0.01).
CONCLUSION: Salvianolate improves liver histopathological changes, repairs intestinal mucosa and TJ structure, and enhances ZO-1 expression in the small intestinal mucosa in cirrhotic rats.
PMCID: PMC3531692  PMID: 23323006
Salvianolate; Cirrhosis; Gut barrier; Tight junction; Zonula occludens protein 1
14.  Activated mouse CD4+Foxp3− T cells facilitate melanoma metastasis via Qa-1-dependent suppression of NK-cell cytotoxicity 
Cell Research  2012;22(12):1696-1706.
The regulatory activities of mouse CD4+Foxp3+ T cells on various immune cells, including NK cells, have been well documented. Under some conditions, conventional CD4+Foxp3− T cells in the periphery are able to acquire inhibitory function on other T cells, but their roles in controlling innate immune cells are poorly defined. As a potential cellular therapy for cancer, ex vivo activated CD4+Foxp3− effector T cells are often infused back in vivo to suppress tumor growth and metastasis. Whether such activated T cells could affect NK-cell control of tumorigenesis is unclear. In the present study, we found that mitogen-activated CD4+Foxp3− T cells exhibited potent suppressor function on NK-cell proliferation and cytotoxicity in vitro, and notably facilitated B16 melanoma metastasis in vivo. Suppression of NK cells by activated CD4+Foxp3− T cells is cell-cell contact dependent and is mediated by Qa-1:NKG2A interaction, as administration of antibodies blocking either Qa-1 or NKG2A could completely reverse this suppression, and significantly inhibited otherwise facilitated melanoma metastasis. Moreover, activated CD4+Foxp3− cells from Qa-1 knockout mice completely lost the suppressor activity on NK cells, and failed to facilitate melanoma metastasis when transferred in vivo. Taken together, our findings indicate that innate anti-tumor response is counter regulated by the activation of adaptive immunity, a phenomenon we term as “activation-induced inhibition”. Thus, the regulatory role of activated CD4+Foxp3− T cells in NK-cell activity must be taken into consideration in the future design of cancer therapies.
PMCID: PMC3515753  PMID: 22945357
NK cells; T cells; suppression; melanoma; metastasis; Qa-1
15.  Phylogenetic Analyses of Trichodinids (Ciliophora, Oligohymenophora) Inferred from 18S rRNA Gene Sequence Data 
Current Microbiology  2012;66(3):306-313.
Partial 18S rRNA gene sequences of the three trichodinids, namely Trichodina modesta Lom, 1970, Trichodina paraheterodentata Tang and Zhao 2012. and Trichodinella epizootica (Raabe 1950) Šrámek-Hušek, 1953, were acquired and used to construct phylogenetic trees. The results revealed that Trichodinella epizootica clustered with Trichodinella sp.; Trichodina paraheterodentata Tang and Zhao 2012 was sister to the clade composed of Trichodina heterodentata Duncan, 1977 and Trichodinanobilis Chen, 1963; Trichodina modesta Lom, 1970 clustered with Trichodina reticulata Hirschman and Partsch, 1955. The branching order of species within the Mobilia clade was closely correlated with GC content. Furthermore, blade morphology was also found to be the primary morphological character in determining the phylogenetic relationships among members of the genus Trichodina. The present findings suggest that the genus Trichodina is paraphyletic when species of Trichodinella are included in the analyses.
PMCID: PMC3557388  PMID: 23196703
16.  Fabrication and spectroscopic investigation of branched silver nanowires and nanomeshworks 
Nanoscale Research Letters  2012;7(1):596.
Wide wavelength ranges of light localization and scattering characteristics can be attributed to shape-dependent longitude surface plasmon resonance in complicated nanostructures. We have studied this phenomenon by spectroscopic measurement and a three-dimensional numerical simulation, for the first time, on the high-density branched silver nanowires and nanomeshworks at room temperature. These nanostructures were fabricated with simple light-induced colloidal method. In the range from the visible to the near-infrared wavelengths, light has been found effectively trapped in those trapping sites which were randomly distributed at the corners, the branches, and the junctions of the nanostructures in those nanostructures in three dimensions. The broadened bandwidth electromagnetic field enhancement property makes these branched nanostructures useful in optical processing and photovoltaic applications.
PMCID: PMC3577568  PMID: 23101991
Silver Nanowires; Nanomeshworks; Branched nanostructures; Localized surface plasmon resonance; Hot spots; Bandwidth
17.  Lipoprotein lipase deficiency in chronic kidney disease is accompanied by down-regulation of endothelial GPIHBP1 expression 
Chronic renal failure (CRF) is associated with hypertriglyceridemia and impaired clearance of very low density lipoprotein (VLDL) and chylomicrons which are largely due to lipoprotein lipase (LPL) deficiency/dysfunction. After its release from myocytes and adipocytes, LPL binds to the endothelium in the adjacent capillaries where it catalyzes hydrolysis of triglycerides in VLDL and chylomicrons. The novel endothelium-derived molecule, glycosylphosphatidylinositol-anchored binding protein 1 (GPIHBP1), plays a critical role in LPL metabolism and function by anchoring LPL to the endothelium and binding chylomicrons. GPIHBP1-deficient mice and humans exhibit severe hypertriglyceridemia and diminished heparin-releasable LPL, pointing to the critical role of GPIHBP1 in regulation of LPL activity. Given its central role in regulation of LPL activity and triglyceride metabolism, we explored the effect of chronic kidney disease (CKD) on GPIHBP1 expression.
Expression of GPIHBP1 and LPL were determined by reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemical analyses in the adipose tissue, skeletal muscle and myocardium of rats 12 weeks after 5/6 nephrectomy (CRF) or sham-operation (control).
Compared to the controls, the CRF group exhibited severe hypertriglyceridemia, significant reduction of the skeletal muscle, myocardium and adipose tissue LPL mRNA and protein abundance. This was accompanied by parallel reductions of GPIHBP1 mRNA abundance and immunostaining in the tested tissues.
LPL deficiency in CKD is associated with and compounded by GPIHBP1 deficiency. Together these abnormalities contribute to impaired clearance of triglyceride-rich lipoproteins, diminished availability of lipid fuel for energy storage in adipocytes and energy production in myocytes and consequent hypertriglyceridemia, cachexia, muscle weakness and atherosclerosis.
PMCID: PMC3417131  PMID: 22009636
Lipid metabolism; Triglyceride metabolism; Atherosclerosis; Impaired exercise capacity; Malnutrition syndrome; Cardiovascular disease; End-stage renal disease; Muscle and fat tissues
18.  Salutary effects of a novel oxidative stress modulator on adenine-induced chronic progressive tubulointerstitial nephropathy 
Oxidative stress and inflammation promote the development and progression of chronic kidney disease. Oxidative stress is associated with depletion of tissue glutathione (GSH), the most abundant endogenous intracellular antioxidant, but degradation of oral GSH by digestive enzymes limits its therapeutic use. We hypothesized that GSH repletion with F1, a novel oral GSH precursor containing cystine as a cysteine carrier, would restore tissue GSH and attenuate oxidative stress and inflammation, and thereby reduce the severity of interstitial nephropathy in chronic renal failure (CRF).
Male Sprague-Dawley rats (n=5-8) were assigned to 3 groups: Control (regular rat chow), CRF (rat chow containing 0.7% adenine), and F1-treated CRF (rat chow containing 0.7% adenine and F1, 0.5g/kg/day) for 2-weeks. Animals were switched to regular chow and euthanized after 2 additional weeks.
Consumption of 0.7% adenine-containing diet caused azotemia; severe kidney swelling; heavy tubular and glomerular damage; massive tubulointerstitial nephropathy; impaired urinary concentrating capacity; severe anemia; increased markers of oxidative stress, plasma oxidized glutathione disulfide (GSSG); reduced GSH/GSSG ratio and manganese superoxide dismutase; increased expression of inflammatory mediators (cyclooxygenase-2, cytoplasmic NF-κB, p-IκBα, nuclear NF-κB p65), and 3-nitrotyrosine, p<0.05. Co-treatment with F1 significantly attenuated tubulointerstitial inflammation and edema, improved urinary concentrating capacity, azotemia and anemia, and normalized markers of tissue oxidative and nitrosative stress, p<0.05.
The novel oxidative stress modulator, F1, markedly attenuated oxidative stress indicators, inflammation, renal injury and dysfunction in the rat model of CRF. Studies to determine the effects of F1 in other models of acute and CRF are warranted.
PMCID: PMC3426391  PMID: 22937204
Glutathione precursor; oxidative stress modulator; inflammation; glutathione disulfide; p-IκBα; NF-κB; NF-κB p65; hematocrit
19.  Thrombolytic effects of Douchi Fibrinolytic enzyme from Bacillus subtilis LD-8547 in vitro and in vivo 
BMC Biotechnology  2012;12:36.
Today, thrombosis is one of the most widely occurring diseases in modern life. Drugs with thrombolytic functions are the most effective methods in the treatment of thrombosis. Among them, Douchi fibrinolytic enzyme (DFE) is a promising agent. DFE was isolated from Douchi, a typical and popular soybean-fermented food in China, and it can dissolve fibrin directly and efficiently. A strain, Bacillus subtilis LD-8547 produced DFE with high fibrinolytic activity has been isolated in our lab previously.
In the study, thrombolytic effect of DFE from Bacillus subtilis LD-8547 was studied in vitro and in vivo systematically. The results showed that DFE played a significant role in thrombolysis and anticoagulation in vitro. And the thrombolytic effects correlated with DFE in a dose-dependent manner. In vivo, the acute toxicity assay showed that DFE had no obvious acute toxicity to mice. Test of carrageenan-induced thrombosis in mice indicated that the DFE significantly prevented tail thrombosis, and arterial thrombosis model test indicated that Douchi fibrinolytic enzyme DFE had thrombolytic effect on carotid thrombosis of rabbits in vivo. Other results in vivo indicated that DFE could increase bleeding and clotting time obviously.
The DFE isolated from Bacillus subtilis LD-8547 has obvious thrombolytic effects in vitro and in vivo. This function demonstrates that this enzyme can be a useful tool for preventing and treating clinical thrombus.
PMCID: PMC3434014  PMID: 22748219
Thrombolytic effects; Douchi Fibrinolytic enzyme; in vitro; in vivo
20.  Oncogenic reg IV is a novel prognostic marker for glioma patient survival 
Diagnostic Pathology  2012;7:69.
The aberrant expression of regenerating islet-derived family member, 4 (Reg IV) has been found in various human cancers. However, the roles of Reg IV gene and its encoding product in human glioma have not been clearly understood. Therefore, the aim of this study was to investigate the clinicopathological significance of Reg IV expression in glioma.
Reg IV mRNA and protein expression in human gliomas and non-neoplastic brain tissues were respectively detected by real-time quantitative RT-PCR assay, Western blot, and immunohistochemistry. The association of Reg IV immunostaining with clinicopathological factors and prognosis of glioma patients was also statistically analyzed.
Reg IV mRNA and protein expression levels in glioma tissues were both significantly higher than those in the corresponding non-neoplastic brain tissues (both P < 0.001). Additionally, the increased Reg IV immunostaining in glioma tissues was significantly associated with advanced pathological grade (P = 0.008). Reg IV protein up-regulation was also significantly correlated with low Karnofsky performance score (KPS) (P = 0.02). Moreover, the overall survival of patients with high Reg IV protein expression was dramatically shorter than those with low Reg IV protein expression (P < 0.001). Multivariate Cox regression analysis further confirmed that Reg IV expression was an independent prognostic factor for patients with gliomas (P = 0.008).
These convinced evidences suggest for the first time that Reg IV might accelerate disease progression and act as a candidate prognostic marker for gliomas.
Virtual slides
The virtual slide(s) for this article can be found here:
PMCID: PMC3465175  PMID: 22713481
Regenerating islet-derived family member 4; glioma; RT-PCR; Western blot; Immunohistochemistry; Prognosis
21.  C5a and its receptors in human anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis 
Arthritis Research & Therapy  2012;14(3):R140.
The complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In particular, C5a plays a central role. In this study, plasma and urinary levels of C5a as well as renal C5a receptors (CD88 and C5L2) expression were investigated in patients with AAV.
Twenty-four patients with AAV in the active phase, 19 patients with AAV in the remission phase, and 20 patients with lupus nephritis (LN) were included. Plasma and urinary levels of C5a were measured with enzyme-linked immunosorbent assay (ELISA). The staining of CD88 and C5L2 in renal specimens was detected with immunohistochemistry.
The level of plasma C5a was significantly higher in patients with AAV in the active phase than that in patients in remission, that in patients with LN, and that in normal controls. The urinary C5a level was significantly higher in patients with AAV in the active phase than that in patients in remission and that in normal controls, but not significantly different between patients with active AAV and patients with LN. The mean optical density of CD88 staining in the tubulointerstitium was significantly lower in AAV patients than that in normal controls (0.0052 ± 0.0011 versus 0.029 ± 0.0042; P = 0.005). The mean optical density of C5L2 in glomeruli was significantly higher in AAV patients than that in normal controls (0.013 ± 0.0027 versus 0.0032 ± 0.0006; P < 0.001). The mean optical density of CD88 staining closely correlated with the initial eGFR (r = 0.835; P < 0.001) in AAV patients. Double-labeling immunofluorescence assay suggested that CD88 did not express on neutrophils, monocytes, or macrophages, but C5L2 expressed on neutrophils (or monocytes) and macrophages.
The elevated plasma and urinary C5a levels indicated complement activation in human AAV. The level of renal CD88 expression could reflect the disease severity of ANCA-associated glomerulonephritis. CD88 expression was downregulated, and C5L2 was upregulated in ANCA-associated glomerulonephritis.
PMCID: PMC3446523  PMID: 22691190
22.  Genetic Structure of the Tree Peony (Paeonia rockii) and the Qinling Mountains as a Geographic Barrier Driving the Fragmentation of a Large Population 
PLoS ONE  2012;7(4):e34955.
Tree peonies are great ornamental plants associated with a rich ethnobotanical history in Chinese culture and have recently been used as an evolutionary model. The Qinling Mountains represent a significant geographic barrier in Asia, dividing mainland China into northern (temperate) and southern (semi–tropical) regions; however, their flora has not been well analyzed. In this study, the genetic differentiation and genetic structure of Paeonia rockii and the role of the Qinling Mountains as a barrier that has driven intraspecific fragmentation were evaluated using 14 microsatellite markers.
Methodology/Principal Findings
Twenty wild populations were sampled from the distributional range of P. rockii. Significant population differentiation was suggested (FST value of 0.302). Moderate genetic diversity at the population level (HS of 0.516) and high population diversity at the species level (HT of 0.749) were detected. Significant excess homozygosity (FIS of 0.076) and recent population bottlenecks were detected in three populations. Bayesian clusters, population genetic trees and principal coordinate analysis all classified the P. rockii populations into three genetic groups and one admixed Wenxian population. An isolation-by-distance model for P. rockii was suggested by Mantel tests (r = 0.6074, P<0.001) and supported by AMOVA (P<0.001), revealing a significant molecular variance among the groups (11.32%) and their populations (21.22%). These data support the five geographic boundaries surrounding the Qinling Mountains and adjacent areas that were detected with Monmonier's maximum-difference algorithm.
Our data suggest that the current genetic structure of P. rockii has resulted from the fragmentation of a formerly continuously distributed large population following the restriction of gene flow between populations of this species by the Qinling Mountains. This study provides a fundamental genetic profile for the conservation and responsible exploitation of the extant germplasm of this species and for improving the genetic basis for breeding its cultivars.
PMCID: PMC3327690  PMID: 22523566
23.  Aberrant Expression of N-Methylpurine-DNA Glycosylase Influences Patient Survival in Malignant Gliomas 
Aim. To examine the expression of N-methylpurine-DNA glycosylase (MPG) gene and protein in glioma samples with different WHO grades and its association with patients' survival. Methods. Immunohistochemistry assay, quantitative real-time PCR and Western blot analysis were carried out to investigate the expression of MPG gene and protein in 128 glioma and 10 non-neoplastic brain tissues. Results. MPG gene expression level in glioma tissues was significantly higher than that in non-neoplastic brain tissues (P < 0.001). Immunohistochemistry also showed that MPG protein was over-expressed in glioma tissues, which was consistent with the resutls of Western blot analysis. Additionally, the expression levels of MPG gene and protein both increase from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry and western blot analysis. Moreover, the survival rate of MPG-positive patients was significantly lower than that of MPG-negative patients (P < 0.001). We further confirmed that the over-expression of MPG was a significant and independent prognostic indicator in glioma by multivariate analysis (P < 0.001). Conclusions. Our data showed the over-expression of MPG gene and protein in human gliomas, and also suggested for the first time that MPG be an unfavorable independent prognostic indicator for glioma patients.
PMCID: PMC3303893  PMID: 22496614
24.  Acute infarct of the corpus callosum presenting as alien hand syndrome: evidence of diffusion weighted imaging and magnetic resonance angiography 
BMC Neurology  2011;11:142.
Infarcts of the corpus callosum are rare and have not been well documented previously. As for a variety of signs and symptoms presented, alien hand syndrome (AHS) can be easily overlooked.
Case presentation
In this report, we present a patient with a mixed types of AHS coexistence secondary to the corpus callosum infarction, including a motor type of AHS by intermanual conflict (callosal type AHS) and a sensory type of AHS by alien hand and left hemianesthesia (posterior AHS).
Our case may contribute to the early recognition of AHS and to explore the abnormal neural mechanism of AHS. To our knowledge, rare reports have ever documented such mixed AHS coexisting secondary to the callosal lesion, based on advanced neuroimaging methods as in our case.
PMCID: PMC3269990  PMID: 22067592
25.  High-calorie diet partially ameliorates dysregulation of intrarenal lipid metabolism in remnant kidney 
Chronic renal failure (CRF) is associated with malnutrition and renal tissue accumulation of lipids, which can contribute to progression of renal disease. This study was designed to explore the effect of a high-calorie diet on pathways involved in lipid metabolism in the remnant kidney of rats with CRF. 5/6 nephrectomized rats were randomized to receive a regular diet (3.0 kcal/g) or a high-calorie diet (4.5 kcal/g) for 12 weeks. Renal lipid contents and abundance of molecules involved in cholesterol and fatty acid metabolism were studied. The CRF group consuming a regular diet exhibited growth retardation; azotemia; proteinuria; glomerulosclerosis; tubulointerstitial injury; heavy lipid accumulation in the remnant kidney; up-regulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), ATP-binding cassette transporter-1 (ABCA1), liver X receptor (LXR) α/β, carbohydrate-responsive element binding protein (ChREBP) and acyl-CoA carboxylase (ACC); and down-regulation of peroxisome proliferator-activated receptor-α (PPAR-α), carnitine palmitoyltransferase-1 (CPT1) and liver-type fatty acid binding protein (L-FABP). The high-calorie diet restored growth; reduced the severity of tubulointerstitial injury, proteinuria and azotemia; partially lowered renal tissue lipid contents; attenuated the up-regulation of mediators of lipid influx (LOX-1), lipid efflux (LXR-α/β and ABCA1) and fatty acid biosynthesis (ChREBP and ACC); and reversed the down-regulation of factors involved in fatty acid oxidation (PPAR-α, CPT1 and L-FABP). In conclusion, a high-calorie diet restores growth, improves renal function and structure, and lowers lipid burden in the remnant kidney. The latter is associated with and most likely due to reduction in lipid influx and enhancement of fatty acid oxidation.
PMCID: PMC3206097  PMID: 19954950
Chronic kidney disease; Renal lipid metabolism; Malnutrition; Inflammation; Progression of renal disease; Reverse cholesterol transport

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